1 Title Page
Not populated in this demonstration. E3 lists 14 required title-page fields, including study title, protocol identifier, indication, a brief statement of design, investigational product, study phase, study initiation/completion dates, sponsor and responsible medical officer, and a statement of GCP compliance.
2 Synopsis
Not populated in this demonstration. E3 Annex I gives a worked example; usually limited to 3 pages.
3 Table of Contents for the Individual Clinical Study Report
Not populated in this demonstration. Generated by the assembler from the populated section tree.
4 List of Abbreviations and Definition of Terms
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5 Ethics
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5.1 Independent Ethics Committee (IEC) or Institutional Review Board (IRB)
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5.2 Ethical Conduct of the Study
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the International Council for Harmonisation Guideline for Good Clinical Practice (ICH E6) and the applicable regulatory requirements of the jurisdictions in which the study was conducted.
The protocol, the protocol amendments, the patient information sheet and the informed consent form were reviewed and approved by the responsible independent ethics committee or institutional review board at each participating centre before any patient was screened. Substantial amendments were submitted for review and approved before implementation, except where an immediate change was necessary to eliminate a hazard to patients.
TXT-E3-0502 · boilerplate
5.3 Patient Information and Consent
Written informed consent was obtained from every patient, or from the patient's legally acceptable representative where the patient was not competent to consent, before any study-specific procedure was performed. Because the study enrolled patients with mild to moderate Alzheimer's disease, the consent process explicitly provided for assessment of decisional capacity and, where capacity was impaired, for consent by a legally acceptable representative together with the assent of the patient.
Patients and their representatives were informed of the objectives of the study, of the investigational nature of the treatment, of the reasonably foreseeable risks and inconveniences, and of their right to withdraw from the study at any time without penalty or loss of benefits to which they were otherwise entitled. A copy of the signed consent form was provided to each patient or representative. The patient information sheet and the sample consent form are provided in Section 16.1.3.
TXT-E3-0503 · boilerplate
6 Investigators and Study Administrative Structure
Not populated in this demonstration. Details cross-reference Appendix 16.1.4.
7 Introduction
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8 Study Objectives
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9 Investigational Plan
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9.1 Overall Study Design and Plan: Description
This was a randomised, double-blind, placebo-controlled, parallel-group study of the Xanomeline Transdermal Therapeutic System (TTS) in patients with mild to moderate Alzheimer's disease. Patients who satisfied all entry criteria at screening were randomised in equal allocation to one of three treatment groups — placebo, xanomeline low dose, or xanomeline high dose — and treated for the planned treatment period defined in the protocol, followed by an end-of-study evaluation.
A total of 254 patients were randomised and treated: 86 to placebo, 96 to xanomeline low dose and 72 to xanomeline high dose. Patients who were screened but not randomised are excluded from all analyses presented in this report; the derivation of the analysis populations is described in Section 11.1.
Study drug was supplied as a transdermal patch applied once daily. The blind was maintained by supplying placebo and active patches of identical appearance, and by withholding the randomisation code from investigators, patients and study personnel involved in the conduct of the study until database lock. The randomisation scheme and codes are provided in Section 16.1.7.
TXT-E3-0901 · parameterized
9.2 Discussion of Study Design, Including the Choice of Control Groups
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9.3 Selection of Study Population
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9.3.1 Inclusion Criteria
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9.3.2 Exclusion Criteria
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9.3.3 Removal of Patients from Therapy or Assessment
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9.4 Treatments
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9.4.1 Treatments Administered
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9.4.2 Identity of Investigational Product(s)
Not populated in this demonstration. Batch listing, where more than one batch was used, goes to 16.1.6.
9.4.3 Method of Assigning Patients to Treatment Groups
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9.4.4 Selection of Doses in the Study
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9.4.5 Selection and Timing of Dose for Each Patient
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9.4.6 Blinding
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9.4.7 Prior and Concomitant Therapy
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9.4.8 Treatment Compliance
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9.5 Efficacy and Safety Variables
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9.5.1 Efficacy and Safety Measurements Assessed and Flow Chart
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9.5.2 Appropriateness of Measurements
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9.5.3 Primary Efficacy Variable(s)
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9.5.4 Drug Concentration Measurements
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9.6 Data Quality Assurance
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9.7 Statistical Methods Planned in the Protocol and Determination of Sample Size
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9.7.1 Statistical and Analytical Plans
Not populated in this demonstration. Full documentation of statistical methods belongs in Appendix 16.1.9.
9.7.2 Determination of Sample Size
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9.8 Changes in the Conduct of the Study or Planned Analyses
No changes were made to the conduct of the study after the first patient was randomised, other than those recorded in the protocol amendments provided in Section 16.1.1.
The analyses presented in this report follow the statistical analysis plan. Every analysis was executed from version-controlled specifications, and each regeneration of a display is recorded as a numbered iteration with the specification hash, the input dataset hashes and the software environment that produced it. Any analysis performed after the statistical analysis plan was finalised is identified as post hoc where it appears. The complete documentation of statistical methods, including the specification and environment provenance for every display in this report, is provided in Section 16.1.9.
TXT-E3-0908 · boilerplate
10 Study Patients
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10.1 Disposition of Patients
Of the 254 patients randomised and treated, 110 (43.3%) completed the study and 144 (56.7%) discontinued prematurely.
Completion was substantially lower in both xanomeline groups than in the placebo group. 58 of the 86 patients randomised to placebo (67.4%) completed the study, compared with 25 of 96 (26.0%) in the xanomeline low dose group and 27 of 72 (37.5%) in the xanomeline high dose group. Premature discontinuation was therefore about twice as frequent in the xanomeline groups as in the placebo group, and this imbalance is the dominant feature of study conduct.
Death was recorded as the reason for discontinuation in 3 patients: 2 receiving placebo, 1 receiving xanomeline low dose and 0 receiving xanomeline high dose. The remaining 141 discontinuations are recorded in the analysis dataset as other or not specified, so no further breakdown of discontinuation reason is available from these data; the adverse event profile that plausibly accounts for the imbalance is described in Section 12.2.
Patient disposition is summarised in 14.1.1. Individual discontinued patients, with the date and the recorded reason for discontinuation, are listed in Section 16.2.1.
TXT-E3-1001 · parameterized
TXT-E3-1002 is excluded from the assembled document: generated-tier block is draft; excluded from assembly pending human approval.
| Subject Disposition (Summary) | ||||
| Study CDISCPILOT01 — Intent-to-Treat Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Disposition, n (%) | ||||
| Subjects randomised | ||||
| Subjects treated | ||||
| Completed the study | ||||
| Discontinued the study | ||||
| Reason for discontinuation, n (%) | ||||
| Death | ||||
| Other / not specified | ||||
| Deaths, n (%) | ||||
| Died on study | ||||
| Percentages are based on the number of randomised subjects in each treatment group. | ||||
| The ADSL shipped in pharmaverseadam carries no DCSREAS/DCDECOD, so the reason for discontinuation is derived: 'Death' where DTHFL = 'Y', otherwise 'Other / not specified'. | ||||
| 52 screen failures are excluded from every analysis dataset. | ||||
| Source: adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-disposition (in_text variant); generated from the committed ARD. | ||||
10.2 Protocol Deviations
Not populated in this demonstration. Individual deviations are listed in 16.2.2.
11 Efficacy Evaluation
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11.1 Data Sets Analysed
The safety analysis set comprised all patients who were randomised and received at least one dose of study medication. It included 254 patients: 86 in the placebo group, 96 in the xanomeline low dose group and 72 in the xanomeline high dose group. All safety analyses in this report, and every display referenced from Section 12, are based on this analysis set, and each display identifies its analysis set in the header in accordance with ICH E3.
Patients who were screened but not randomised are excluded from every analysis set. Analysis-set membership is derived in a documented, version-controlled data preparation step rather than assumed from the source data; that derivation, and the environment that executed it, are recorded in Section 16.1.9.
No efficacy analysis set is defined for this report. The public ADaM package used as the data source for this demonstration contains no efficacy analysis dataset for this study, so the efficacy sections and the corresponding post-text displays in Section 14.2 are intentionally not populated. Patients excluded from any analysis population would be listed in Section 16.2.3.
TXT-E3-1101 · parameterized
11.2 Demographic and Other Baseline Characteristics
Demographic and baseline characteristics were comparable across the three treatment groups in the safety analysis set of 254 patients.
The study population was elderly, as expected for a mild to moderate Alzheimer's disease population. Mean age overall was 75.1 years (SD 8.25), with a median of 77 years and a range of 51 to 89 years. Mean age was 75.2 years in the placebo group, 76.0 years in the xanomeline low dose group and 73.8 years in the xanomeline high dose group.
Women accounted for 143 patients (56.3%) overall, and the proportion of women ranged from 48.6% in the xanomeline high dose group to 61.6% in the placebo group. The population was predominantly white (230 patients, 90.6%), with 23 patients reported as Black or African American. The limited racial diversity of the population should be considered when generalising the findings of this study.
Demographic and baseline characteristics are summarised in 14.1.2; individual demographic data are listed in Section 16.2.4.
TXT-E3-1102 · parameterized
| Demographic Characteristics (Summary) | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Age (years) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Min, Max | ||||
| Age group, n (%) | ||||
| 18-64 | ||||
| >64 | ||||
| Sex, n (%) | ||||
| F | ||||
| M | ||||
| Race, n (%) | ||||
| WHITE | ||||
| BLACK OR AFRICAN AMERICAN | ||||
| AMERICAN INDIAN OR ALASKA NATIVE | ||||
| Ethnicity, n (%) | ||||
| HISPANIC OR LATINO | ||||
| NOT HISPANIC OR LATINO | ||||
| Baseline weight (kg) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Min, Max | ||||
| Baseline height (cm) | ||||
| Mean (SD) | ||||
| Min, Max | ||||
| Baseline BMI (kg/m2) | ||||
| Mean (SD) | ||||
| Min, Max | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| Baseline weight, height and body mass index are the ADVS records flagged ABLFL = 'Y'. | ||||
| Source: adsl (pharmaverseadam), baseline vital signs from advs. Data cut-off: 2014-07-01. | ||||
| open.csr display t-demographics (in_text variant); generated from the committed ARD. | ||||
11.3 Measurements of Treatment Compliance
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11.4 Efficacy Results and Tabulations of Individual Patient Data
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11.4.1 Analysis of Efficacy
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11.4.2 Statistical/Analytical Issues
Not populated in this demonstration. E3 enumerates eight statistical issues; each is a reusable prose block in the Text Library.
11.4.2.1 Adjustments for Covariates
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11.4.2.2 Handling of Dropouts or Missing Data
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11.4.2.3 Interim Analyses and Data Monitoring
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11.4.2.4 Multicentre Studies
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11.4.2.5 Multiple Comparison/Multiplicity
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11.4.2.6 Use of an "Efficacy Subset" of Patients
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11.4.2.7 Active-Control Studies Intended to Show Equivalence
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11.4.2.8 Examination of Subgroups
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11.4.3 Tabulation of Individual Response Data
Not populated in this demonstration. Cross-references the listings in 16.2.6.
11.4.4 Drug Dose, Drug Concentration, and Relationships to Response
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11.4.5 Drug-Drug and Drug-Disease Interactions
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11.4.6 By-Patient Displays
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11.4.7 Efficacy Conclusions
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12 Safety Evaluation
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12.1 Extent of Exposure
Exposure to study drug was longest in the placebo group and shortest in the xanomeline low dose group, a direct consequence of the discontinuation pattern described in Section 10.1. The imbalance must be taken into account when interpreting crude adverse event frequencies.
Mean duration of exposure was 147.8 days (SD 62.13) in the placebo group, 85.9 days (SD 70.66) in the xanomeline low dose group and 112.2 days (SD 65.52) in the xanomeline high dose group. The corresponding medians were 182.0, 62.5 and 96.5 days. Individual exposure ranged from 0 to 212 days across the safety analysis set.
Cumulative exposure thresholds show the same pattern. At least 30 days of exposure was achieved by 78 patients (90.7%) receiving placebo, 65 (67.7%) receiving xanomeline low dose and 67 (93.1%) receiving xanomeline high dose. Long-term exposure of at least 180 days was reached by 55 patients (64.0%) in the placebo group, against 25 (26.0%) and 26 (36.1%) in the low and high dose groups respectively — so fewer than half as many xanomeline patients as placebo patients reached the long-term exposure threshold.
Extent of exposure, including total and average daily dose, is summarised in 14.3.1.1.
TXT-E3-1201 · parameterized
| Extent of Exposure (Summary) | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Duration of exposure (days) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Q1, Q3 | ||||
| Min, Max | ||||
| Total dose administered (mg) | ||||
| Mean (SD) | ||||
| Median | ||||
| Min, Max | ||||
| Average daily dose (mg) | ||||
| Mean (SD) | ||||
| Median | ||||
| Overall dose intensity (%) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Cumulative exposure, n (%) | ||||
| ≥ 1 day | ||||
| ≥ 30 days | ||||
| ≥ 90 days | ||||
| ≥ 180 days | ||||
| Duration, total dose, average daily dose and dose intensity are the overall-study ADEX parameters TDURD, TDOSE, AVDDSE and TDOSINT respectively. | ||||
| Exposure categories are cumulative: a subject exposed for 200 days is counted in every category up to 180 days. | ||||
| Q1 and Q3 are type-2 (SAS-compatible) quantiles, as computed by {cards}; they differ from R’s default type-7 quantiles. | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| Placebo subjects have no ADEX dose-intensity (TDOSINT) records because planned placebo dose is zero; the dose-intensity rows are therefore empty for that column. | ||||
| Source: adex, adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-exposure (in_text variant); generated from the committed ARD. | ||||
12.2 Adverse Events (AEs)
Not populated in this demonstration.
12.2.1 Brief Summary of Adverse Events
Treatment-emergent adverse events were reported by 217 of the 254 patients in the safety analysis set (85.4%), covering 1122 individual adverse event records.
The proportion of patients reporting at least one treatment-emergent adverse event rose with dose: 75.6% of patients receiving placebo, 87.5% receiving xanomeline low dose and 94.4% receiving xanomeline high dose. The same gradient was present, and more pronounced, for adverse events assessed by the investigator as related to study drug, reported by 43 patients (50.0%), 77 patients (80.2%) and 64 patients (88.9%) respectively.
Most events were of mild or moderate maximum severity. Severe events were reported by 5 patients (5.8%) receiving placebo, 16 patients (16.7%) receiving xanomeline low dose and 8 patients (11.1%) receiving xanomeline high dose; moderate events were reported by 129 patients (50.8%) overall.
Serious adverse events were uncommon in this study. They were reported by 3 patients (1.2%) overall: 0 receiving placebo, 2 receiving xanomeline low dose and 1 receiving xanomeline high dose. Adverse events with a fatal outcome were recorded for 3 patients, of whom 2 were receiving placebo. Deaths and serious adverse events are described in Section 12.3.
An overview of treatment-emergent adverse events is presented in 14.3.1.2. Because exposure differed substantially between the groups (Section 12.1), the crude proportions above should be read alongside the exposure summary.
TXT-E3-1221 · parameterized
| Overview of Treatment-Emergent Adverse Events (Summary) | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Adverse events | ||||
| Number of events | ||||
| Subjects with ≥1 adverse event | ||||
| Subjects with a serious adverse event | ||||
| Subjects with a fatal adverse event | ||||
| Subjects with a related adverse event | ||||
| Subjects by severity, n (%) | ||||
| Mild | ||||
| Moderate | ||||
| Severe | ||||
| A treatment-emergent adverse event is an event with TRTEMFL = 'Y'. | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| Subjects reporting more than one event are counted once in each row they qualify for; severity rows count subjects with at least one event of that severity and therefore do not sum to the number of subjects with any event. | ||||
| Source: adae, adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-ae-overview (in_text variant); generated from the committed ARD. | ||||
12.2.2 Display of Adverse Events
TXT-E3-1222 is excluded from the assembled document: generated-tier block is draft; excluded from assembly pending human approval.
| Common Treatment-Emergent Adverse Events (≥5% in any treatment group) | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | ||||
| APPLICATION SITE PRURITUS | ||||
| APPLICATION SITE ERYTHEMA | ||||
| APPLICATION SITE DERMATITIS | ||||
| APPLICATION SITE IRRITATION | ||||
| APPLICATION SITE VESICLES | ||||
| FATIGUE | ||||
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | ||||
| PRURITUS | ||||
| ERYTHEMA | ||||
| RASH | ||||
| HYPERHIDROSIS | ||||
| SKIN IRRITATION | ||||
| BLISTER | ||||
| NERVOUS SYSTEM DISORDERS | ||||
| DIZZINESS | ||||
| HEADACHE | ||||
| SYNCOPE | ||||
| GASTROINTESTINAL DISORDERS | ||||
| DIARRHOEA | ||||
| VOMITING | ||||
| NAUSEA | ||||
| SALIVARY HYPERSECRETION | ||||
| CARDIAC DISORDERS | ||||
| SINUS BRADYCARDIA | ||||
| MYOCARDIAL INFARCTION | ||||
| INFECTIONS AND INFESTATIONS | ||||
| NASOPHARYNGITIS | ||||
| UPPER RESPIRATORY TRACT INFECTION | ||||
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | ||||
| COUGH | ||||
| Reduced variant: only preferred terms reported by at least 5% of subjects in at least one treatment group are shown. The full display is Section 14. | ||||
| Subjects are counted once per system organ class and once per preferred term, regardless of how many events they reported. | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| System organ classes and preferred terms are sorted by descending subject count. | ||||
| The Total column pools all treatment groups; the 5% threshold applied to the in-text variant is evaluated on the treatment columns only, never on Total. | ||||
| Source: adae, adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-ae-common (in_text variant); generated from the committed ARD. | ||||
12.2.3 Analysis of Adverse Events
Not populated in this demonstration.
12.2.4 Listing of Adverse Events by Patient
All treatment-emergent adverse events recorded during the study are listed by patient in Section 16.2.7. The listing gives, for each event, the patient identifier, treatment group, verbatim term, preferred term and system organ class, onset and resolution dates, maximum severity, seriousness, the investigator's assessment of relationship to study drug, the action taken with study drug and the outcome.
Serious adverse events, adverse events with a fatal outcome and adverse events leading to withdrawal of study drug are additionally presented in 14.3.2.1.
Every listing carries the study number, the analysis set and the data cut-off date in its header, and identifies derived values in a conspicuous fashion, as required by ICH E3. Patient identifiers in listings intended for public disclosure are subject to the anonymisation approach described in the study's disclosure plan.
TXT-E3-1224 · boilerplate
12.3 Deaths, Other Serious Adverse Events, and Other Significant Adverse Events
Not populated in this demonstration.
12.3.1 Listing of Deaths, Other Serious Adverse Events and Other Significant Adverse Events
TXT-E3-1231 is excluded from the assembled document: generated-tier block is draft; excluded from assembly pending human approval.
| USUBJID | TRT01A | AGE | SEX | AEBODSYS | AEDECOD | AESEV | AEREL | ASTDY | AENDY | AEOUT |
|---|---|---|---|---|---|---|---|---|---|---|
| 01-709-1424 | Xanomeline Low Dose | 77 | M | NERVOUS SYSTEM DISORDERS | SYNCOPE | MODERATE | POSSIBLE | 5 | 5 | RECOVERED/RESOLVED |
| 01-718-1170 | Xanomeline Low Dose | 80 | F | NERVOUS SYSTEM DISORDERS | SYNCOPE | SEVERE | PROBABLE | 27 | 28 | RECOVERED/RESOLVED |
| 01-718-1371 | Xanomeline High Dose | 69 | F | NERVOUS SYSTEM DISORDERS | PARTIAL SEIZURES WITH SECONDARY GENERALISATION | SEVERE | NONE | 38 | 41 | RECOVERED/RESOLVED |
12.3.1.1 Deaths
Not populated in this demonstration.
12.3.1.2 Other Serious Adverse Events
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12.3.1.3 Other Significant Adverse Events
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12.3.2 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events
Not populated in this demonstration. Prose, not a table — but E3 also reserves 14.3.3 for the narratives. The narratives are a Text Library product built from the same ADaM spine as the AE displays.
12.3.3 Analysis and Discussion of Deaths, Other Serious and Other Significant Adverse Events
Not populated in this demonstration.
12.4 Clinical Laboratory Evaluation
Not populated in this demonstration.
12.4.1 Listing of Individual Laboratory Measurements by Patient and Each Abnormal Laboratory Value
Not populated in this demonstration. Listings appear in 16.2.8; abnormal values also in 14.3.4.
12.4.2 Evaluation of Each Laboratory Parameter
Not populated in this demonstration.
12.4.2.1 Laboratory Values Over Time
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12.4.2.2 Individual Patient Changes
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12.4.2.3 Individual Clinically Significant Abnormalities
Not populated in this demonstration.
12.5 Vital Signs, Physical Findings and Other Observations Related to Safety
Not populated in this demonstration.
12.6 Safety Conclusions
TXT-E3-1206 is excluded from the assembled document: generated-tier block is draft; excluded from assembly pending human approval.
13 Discussion and Overall Conclusions
TXT-E3-1300 is excluded from the assembled document: generated-tier block is draft; excluded from assembly pending human approval.
14 Tables, Figures and Graphs Referred to but not Included in the Text
Not populated in this demonstration. E3's three-level rule: overall summaries may sit in the text, other summary tables/figures/listings belong here, individual patient data go to 16.2, and all individual data (US archival) to 16.4.
14.1 Demographic Data
| Subject Disposition | ||||
| Study CDISCPILOT01 — Intent-to-Treat Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Disposition, n (%) | ||||
| Subjects randomised | ||||
| Subjects treated | ||||
| Completed the study | ||||
| Discontinued the study | ||||
| Reason for discontinuation, n (%) | ||||
| Death | ||||
| Other / not specified | ||||
| Deaths, n (%) | ||||
| Died on study | ||||
| Percentages are based on the number of randomised subjects in each treatment group. | ||||
| The ADSL shipped in pharmaverseadam carries no DCSREAS/DCDECOD, so the reason for discontinuation is derived: 'Death' where DTHFL = 'Y', otherwise 'Other / not specified'. | ||||
| 52 screen failures are excluded from every analysis dataset. | ||||
| Source: adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-disposition (post_text variant); generated from the committed ARD. | ||||
| Demographic and Baseline Characteristics | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Age (years) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Min, Max | ||||
| Age group, n (%) | ||||
| 18-64 | ||||
| >64 | ||||
| Sex, n (%) | ||||
| F | ||||
| M | ||||
| Race, n (%) | ||||
| WHITE | ||||
| BLACK OR AFRICAN AMERICAN | ||||
| AMERICAN INDIAN OR ALASKA NATIVE | ||||
| Ethnicity, n (%) | ||||
| HISPANIC OR LATINO | ||||
| NOT HISPANIC OR LATINO | ||||
| Baseline weight (kg) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Min, Max | ||||
| Baseline height (cm) | ||||
| Mean (SD) | ||||
| Min, Max | ||||
| Baseline BMI (kg/m2) | ||||
| Mean (SD) | ||||
| Min, Max | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| Baseline weight, height and body mass index are the ADVS records flagged ABLFL = 'Y'. | ||||
| Source: adsl (pharmaverseadam), baseline vital signs from advs. Data cut-off: 2014-07-01. | ||||
| open.csr display t-demographics (post_text variant); generated from the committed ARD. | ||||
14.2 Efficacy Data
Not populated in this demonstration.
14.3 Safety Data
Not populated in this demonstration.
14.3.1 Displays of Adverse Events
| Extent of Exposure to Study Drug | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Duration of exposure (days) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Q1, Q3 | ||||
| Min, Max | ||||
| Total dose administered (mg) | ||||
| Mean (SD) | ||||
| Median | ||||
| Min, Max | ||||
| Average daily dose (mg) | ||||
| Mean (SD) | ||||
| Median | ||||
| Overall dose intensity (%) | ||||
| n | ||||
| Mean (SD) | ||||
| Median | ||||
| Cumulative exposure, n (%) | ||||
| ≥ 1 day | ||||
| ≥ 30 days | ||||
| ≥ 90 days | ||||
| ≥ 180 days | ||||
| Duration, total dose, average daily dose and dose intensity are the overall-study ADEX parameters TDURD, TDOSE, AVDDSE and TDOSINT respectively. | ||||
| Exposure categories are cumulative: a subject exposed for 200 days is counted in every category up to 180 days. | ||||
| Q1 and Q3 are type-2 (SAS-compatible) quantiles, as computed by {cards}; they differ from R’s default type-7 quantiles. | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| Placebo subjects have no ADEX dose-intensity (TDOSINT) records because planned placebo dose is zero; the dose-intensity rows are therefore empty for that column. | ||||
| Source: adex, adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-exposure (post_text variant); generated from the committed ARD. | ||||
| Overview of Treatment-Emergent Adverse Events | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| Adverse events | ||||
| Number of events | ||||
| Subjects with ≥1 adverse event | ||||
| Subjects with a serious adverse event | ||||
| Subjects with a fatal adverse event | ||||
| Subjects with a related adverse event | ||||
| Subjects by severity, n (%) | ||||
| Mild | ||||
| Moderate | ||||
| Severe | ||||
| A treatment-emergent adverse event is an event with TRTEMFL = 'Y'. | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| Subjects reporting more than one event are counted once in each row they qualify for; severity rows count subjects with at least one event of that severity and therefore do not sum to the number of subjects with any event. | ||||
| Source: adae, adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-ae-overview (post_text variant); generated from the committed ARD. | ||||
| Treatment-Emergent Adverse Events by System Organ Class and Preferred Term | ||||
| Study CDISCPILOT01 — Safety Analysis Set | ||||
| Placebo (N=86) | Xanomeline Low Dose (N=96) | Xanomeline High Dose (N=72) | Total (N=254) | |
|---|---|---|---|---|
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | ||||
| APPLICATION SITE PRURITUS | ||||
| APPLICATION SITE ERYTHEMA | ||||
| APPLICATION SITE DERMATITIS | ||||
| APPLICATION SITE IRRITATION | ||||
| APPLICATION SITE VESICLES | ||||
| FATIGUE | ||||
| OEDEMA PERIPHERAL | ||||
| APPLICATION SITE SWELLING | ||||
| APPLICATION SITE URTICARIA | ||||
| CHILLS | ||||
| MALAISE | ||||
| PYREXIA | ||||
| APPLICATION SITE PAIN | ||||
| APPLICATION SITE PERSPIRATION | ||||
| APPLICATION SITE REACTION | ||||
| ASTHENIA | ||||
| CHEST DISCOMFORT | ||||
| CHEST PAIN | ||||
| OEDEMA | ||||
| PAIN | ||||
| APPLICATION SITE BLEEDING | ||||
| APPLICATION SITE DESQUAMATION | ||||
| APPLICATION SITE DISCHARGE | ||||
| APPLICATION SITE DISCOLOURATION | ||||
| APPLICATION SITE INDURATION | ||||
| APPLICATION SITE WARMTH | ||||
| FEELING ABNORMAL | ||||
| FEELING COLD | ||||
| INFLAMMATION | ||||
| SECRETION DISCHARGE | ||||
| SUDDEN DEATH | ||||
| SWELLING | ||||
| ULCER | ||||
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | ||||
| PRURITUS | ||||
| ERYTHEMA | ||||
| RASH | ||||
| HYPERHIDROSIS | ||||
| SKIN IRRITATION | ||||
| BLISTER | ||||
| RASH PRURITIC | ||||
| PRURITUS GENERALISED | ||||
| URTICARIA | ||||
| ACTINIC KERATOSIS | ||||
| ALOPECIA | ||||
| COLD SWEAT | ||||
| DERMATITIS CONTACT | ||||
| DRUG ERUPTION | ||||
| RASH ERYTHEMATOUS | ||||
| RASH MACULO-PAPULAR | ||||
| SKIN EXFOLIATION | ||||
| SKIN ODOUR ABNORMAL | ||||
| SKIN ULCER | ||||
| NERVOUS SYSTEM DISORDERS | ||||
| DIZZINESS | ||||
| HEADACHE | ||||
| SYNCOPE | ||||
| SOMNOLENCE | ||||
| TRANSIENT ISCHAEMIC ATTACK | ||||
| BURNING SENSATION | ||||
| LETHARGY | ||||
| AMNESIA | ||||
| BALANCE DISORDER | ||||
| COGNITIVE DISORDER | ||||
| COMPLEX PARTIAL SEIZURES | ||||
| COORDINATION ABNORMAL | ||||
| HEMIANOPIA HOMONYMOUS | ||||
| HYPERSOMNIA | ||||
| PARAESTHESIA | ||||
| PARAESTHESIA ORAL | ||||
| PARKINSON'S DISEASE | ||||
| PAROSMIA | ||||
| PARTIAL SEIZURES WITH SECONDARY GENERALISATION | ||||
| PSYCHOMOTOR HYPERACTIVITY | ||||
| STUPOR | ||||
| SYNCOPE VASOVAGAL | ||||
| GASTROINTESTINAL DISORDERS | ||||
| DIARRHOEA | ||||
| VOMITING | ||||
| NAUSEA | ||||
| ABDOMINAL PAIN | ||||
| SALIVARY HYPERSECRETION | ||||
| DYSPEPSIA | ||||
| ABDOMINAL DISCOMFORT | ||||
| CONSTIPATION | ||||
| DYSPHAGIA | ||||
| FLATULENCE | ||||
| GASTROINTESTINAL HAEMORRHAGE | ||||
| GASTROOESOPHAGEAL REFLUX DISEASE | ||||
| GLOSSITIS | ||||
| HIATUS HERNIA | ||||
| RECTAL HAEMORRHAGE | ||||
| STOMACH DISCOMFORT | ||||
| CARDIAC DISORDERS | ||||
| SINUS BRADYCARDIA | ||||
| MYOCARDIAL INFARCTION | ||||
| ATRIAL FIBRILLATION | ||||
| SUPRAVENTRICULAR EXTRASYSTOLES | ||||
| VENTRICULAR EXTRASYSTOLES | ||||
| ATRIAL FLUTTER | ||||
| ATRIOVENTRICULAR BLOCK FIRST DEGREE | ||||
| BUNDLE BRANCH BLOCK RIGHT | ||||
| PALPITATIONS | ||||
| ATRIAL HYPERTROPHY | ||||
| ATRIOVENTRICULAR BLOCK SECOND DEGREE | ||||
| BRADYCARDIA | ||||
| BUNDLE BRANCH BLOCK LEFT | ||||
| CARDIAC DISORDER | ||||
| CARDIAC FAILURE CONGESTIVE | ||||
| SINUS ARRHYTHMIA | ||||
| SUPRAVENTRICULAR TACHYCARDIA | ||||
| TACHYCARDIA | ||||
| VENTRICULAR HYPERTROPHY | ||||
| WOLFF-PARKINSON-WHITE SYNDROME | ||||
| INFECTIONS AND INFESTATIONS | ||||
| NASOPHARYNGITIS | ||||
| UPPER RESPIRATORY TRACT INFECTION | ||||
| INFLUENZA | ||||
| URINARY TRACT INFECTION | ||||
| CYSTITIS | ||||
| EAR INFECTION | ||||
| BRONCHITIS | ||||
| CELLULITIS | ||||
| CERVICITIS | ||||
| GASTROENTERITIS VIRAL | ||||
| HORDEOLUM | ||||
| LOCALISED INFECTION | ||||
| LOWER RESPIRATORY TRACT INFECTION | ||||
| PNEUMONIA | ||||
| RHINITIS | ||||
| VAGINAL MYCOSIS | ||||
| VIRAL INFECTION | ||||
| PSYCHIATRIC DISORDERS | ||||
| CONFUSIONAL STATE | ||||
| AGITATION | ||||
| INSOMNIA | ||||
| ANXIETY | ||||
| DELUSION | ||||
| IRRITABILITY | ||||
| COMPLETED SUICIDE | ||||
| DELIRIUM | ||||
| DEPRESSED MOOD | ||||
| DISORIENTATION | ||||
| HALLUCINATION | ||||
| HALLUCINATION, VISUAL | ||||
| LIBIDO DECREASED | ||||
| LISTLESS | ||||
| NIGHTMARE | ||||
| RESTLESSNESS | ||||
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | ||||
| COUGH | ||||
| NASAL CONGESTION | ||||
| DYSPNOEA | ||||
| EPISTAXIS | ||||
| PHARYNGOLARYNGEAL PAIN | ||||
| RHINORRHOEA | ||||
| ALLERGIC GRANULOMATOUS ANGIITIS | ||||
| DYSPHONIA | ||||
| EMPHYSEMA | ||||
| HAEMOPTYSIS | ||||
| PHARYNGEAL ERYTHEMA | ||||
| POSTNASAL DRIP | ||||
| PRODUCTIVE COUGH | ||||
| RALES | ||||
| RESPIRATORY TRACT CONGESTION | ||||
| INVESTIGATIONS | ||||
| ELECTROCARDIOGRAM ST SEGMENT DEPRESSION | ||||
| ELECTROCARDIOGRAM T WAVE INVERSION | ||||
| BLOOD GLUCOSE INCREASED | ||||
| ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED | ||||
| BIOPSY | ||||
| BIOPSY PROSTATE | ||||
| BLOOD ALKALINE PHOSPHATASE INCREASED | ||||
| BLOOD CHOLESTEROL INCREASED | ||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | ||||
| BLOOD URINE PRESENT | ||||
| BODY TEMPERATURE INCREASED | ||||
| CYSTOSCOPY | ||||
| HEART RATE INCREASED | ||||
| HEART RATE IRREGULAR | ||||
| NASAL MUCOSA BIOPSY | ||||
| WEIGHT DECREASED | ||||
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | ||||
| BACK PAIN | ||||
| ARTHRALGIA | ||||
| SHOULDER PAIN | ||||
| MUSCLE SPASMS | ||||
| ARTHRITIS | ||||
| FLANK PAIN | ||||
| MUSCULAR WEAKNESS | ||||
| MYALGIA | ||||
| PAIN IN EXTREMITY | ||||
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | ||||
| CONTUSION | ||||
| EXCORIATION | ||||
| FALL | ||||
| HIP FRACTURE | ||||
| SKIN LACERATION | ||||
| FACIAL BONES FRACTURE | ||||
| JOINT DISLOCATION | ||||
| WOUND | ||||
| RENAL AND URINARY DISORDERS | ||||
| MICTURITION URGENCY | ||||
| DYSURIA | ||||
| NEPHROLITHIASIS | ||||
| CALCULUS URETHRAL | ||||
| INCONTINENCE | ||||
| POLLAKIURIA | ||||
| METABOLISM AND NUTRITION DISORDERS | ||||
| DECREASED APPETITE | ||||
| FOOD CRAVING | ||||
| INCREASED APPETITE | ||||
| DEHYDRATION | ||||
| DIABETES MELLITUS | ||||
| HYPONATRAEMIA | ||||
| VASCULAR DISORDERS | ||||
| HYPOTENSION | ||||
| HYPERTENSION | ||||
| HOT FLUSH | ||||
| ORTHOSTATIC HYPOTENSION | ||||
| WOUND HAEMORRHAGE | ||||
| EYE DISORDERS | ||||
| VISION BLURRED | ||||
| CONJUNCTIVAL HAEMORRHAGE | ||||
| CONJUNCTIVITIS | ||||
| EYE ALLERGY | ||||
| EYE PRURITUS | ||||
| EYE SWELLING | ||||
| SURGICAL AND MEDICAL PROCEDURES | ||||
| CATARACT OPERATION | ||||
| ACROCHORDON EXCISION | ||||
| EYE LASER SURGERY | ||||
| SKIN LESION EXCISION | ||||
| EAR AND LABYRINTH DISORDERS | ||||
| VERTIGO | ||||
| CERUMEN IMPACTION | ||||
| EAR PAIN | ||||
| CONGENITAL, FAMILIAL AND GENETIC DISORDERS | ||||
| VENTRICULAR SEPTAL DEFECT | ||||
| NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) | ||||
| COLON CANCER | ||||
| MALIGNANT FIBROUS HISTIOCYTOMA | ||||
| PROSTATE CANCER | ||||
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS | ||||
| BENIGN PROSTATIC HYPERPLASIA | ||||
| PELVIC PAIN | ||||
| HEPATOBILIARY DISORDERS | ||||
| HYPERBILIRUBINAEMIA | ||||
| IMMUNE SYSTEM DISORDERS | ||||
| HYPERSENSITIVITY | ||||
| SOCIAL CIRCUMSTANCES | ||||
| ALCOHOL USE | ||||
| Subjects are counted once per system organ class and once per preferred term, regardless of how many events they reported. | ||||
| Percentages are based on the number of subjects in the safety analysis set for each treatment group. | ||||
| System organ classes and preferred terms are sorted by descending subject count. | ||||
| The Total column pools all treatment groups; the 5% threshold applied to the in-text variant is evaluated on the treatment columns only, never on Total. | ||||
| Source: adae, adsl (pharmaverseadam). Data cut-off: 2014-07-01. | ||||
| open.csr display t-ae-common (post_text variant); generated from the committed ARD. | ||||
14.3.2 Listings of Deaths, Other Serious and Significant Adverse Events
| Listing of Serious Adverse Events | |||||||||||
| Study CDISCPILOT01 — Safety Analysis Set | |||||||||||
| Subject | Treatment | Age | Sex | System organ class | Preferred term | Severity | Relationship | Start day | End day | Outcome | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | |||||||||||
| 2 | |||||||||||
| 3 | |||||||||||
| One row per serious adverse event record (AESER = 'Y'). | |||||||||||
| Study day is relative to the first dose of study drug. | |||||||||||
| Source: adae (pharmaverseadam). Data cut-off: 2014-07-01. | |||||||||||
| open.csr display l-ae-serious (post_text variant); generated from the committed ARD. | |||||||||||
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events
Not populated in this demonstration. Prose block inside the TFL section — the Text Library/TFL Library seam.
14.3.4 Abnormal Laboratory Value Listing (Each Patient)
Not populated in this demonstration.
15 Reference List
Not populated in this demonstration.
16 Appendices
Not populated in this demonstration.
16.1 Study Information
Not populated in this demonstration.
16.1.1 Protocol and Protocol Amendments
Not populated in this demonstration.
16.1.2 Sample Case Report Form (unique pages only)
Not populated in this demonstration.
16.1.3 List of IEC or IRB and Representative Written Information for Patient and Sample Consent Forms
Not populated in this demonstration.
16.1.4 List and Description of Investigators and Other Important Participants in the Study, Including Brief CVs or Equivalent Summaries of Training and Experience
Not populated in this demonstration.
16.1.5 Signatures of Principal or Coordinating Investigator(s) or Sponsor's Responsible Medical Officer
Not populated in this demonstration.
16.1.6 Listing of Patients Receiving Test Drug(s)/Investigational Product(s) from Specific Batches, Where More Than One Batch Was Used
Not populated in this demonstration.
16.1.7 Randomisation Scheme and Codes (patient identification and treatment assigned)
Not populated in this demonstration.
16.1.8 Audit Certificates (if available)
Not populated in this demonstration.
16.1.9 Documentation of Statistical Methods
| Item | Value |
|---|---|
| displays[0].slug | t-disposition |
| displays[0].number | 14.1.1 |
| displays[0].title | Subject Disposition |
| displays[0].created | 2026-07-27T03:23:35Z |
| displays[0].specHash | sha256:8c432e510cf8fe58349f0315cb25c51231c261a2276707cfd7168cd064a3d62d |
| displays[0].displayHash | sha256:18ca5acb502028c38848124b04a9db836b79b9072640bf54883c4ca98350a71d |
| displays[0].data[0].dataset | adsl |
| displays[0].data[0].hash | sha256:f9a1c3605cb277363fba0add4c4228df6a288685586575be159718696c582107 |
| displays[0].data[0].n_row | 254 |
| displays[0].data[0].n_col | 60 |
| displays[0].data[0].source_pkg | pharmaverseadam |
| displays[0].data[0].source_version | 1.1.0 |
| displays[0].environment.r | 4.3.3 |
| displays[0].environment.os | Darwin 23.6.0 |
| displays[0].environment.packages.cards | 0.6.1 |
| displays[0].environment.packages.cardx | 0.2.5 |
| displays[0].environment.packages.gtsummary | 2.3.0 |
| displays[0].environment.packages.gt | 1.0.0 |
| displays[0].environment.packages.dplyr | 1.1.4 |
| displays[0].environment.packages.pharmaverseadam | 1.1.0 |
| displays[0].environment.packages.jsonlite | 2.0.0 |
| displays[0].environment.packages.yaml | 2.3.10 |
| displays[0].environment.packages.digest | 0.6.37 |
| displays[0].source | outputs |
| displays[0].ardPath | outputs/t-disposition/v002/ard.json |
| displays[0].fixture | false |
| displays[1].slug | t-demographics |
| displays[1].number | 14.1.2 |
| displays[1].title | Demographic and Baseline Characteristics |
| displays[1].created | 2026-07-27T03:23:35Z |
| displays[1].specHash | sha256:0f1e9b9029b61b70bfa00f93c9f0c52050859ff26cacb67ee2fed50c39392854 |
| displays[1].displayHash | sha256:47d64c3c97e9a311b8b5bfdd7ae6d2a3cb1ff5a6442ad77664da993634c629bd |
| displays[1].data[0].dataset | adsl |
| displays[1].data[0].hash | sha256:f9a1c3605cb277363fba0add4c4228df6a288685586575be159718696c582107 |
| displays[1].data[0].n_row | 254 |
| displays[1].data[0].n_col | 60 |
| displays[1].data[0].source_pkg | pharmaverseadam |
| displays[1].data[0].source_version | 1.1.0 |
| displays[1].environment.r | 4.3.3 |
| displays[1].environment.os | Darwin 23.6.0 |
| displays[1].environment.packages.cards | 0.6.1 |
| displays[1].environment.packages.cardx | 0.2.5 |
| displays[1].environment.packages.gtsummary | 2.3.0 |
| displays[1].environment.packages.gt | 1.0.0 |
| displays[1].environment.packages.dplyr | 1.1.4 |
| displays[1].environment.packages.pharmaverseadam | 1.1.0 |
| displays[1].environment.packages.jsonlite | 2.0.0 |
| displays[1].environment.packages.yaml | 2.3.10 |
| displays[1].environment.packages.digest | 0.6.37 |
| displays[1].source | outputs |
| displays[1].ardPath | outputs/t-demographics/v002/ard.json |
| displays[1].fixture | false |
| displays[2].slug | t-exposure |
| displays[2].number | 14.3.1.1 |
| displays[2].title | Extent of Exposure to Study Drug |
| displays[2].created | 2026-07-27T03:23:36Z |
| displays[2].specHash | sha256:dcb569bb84c890fe5d3322fbb111cdaeabd917ad388c89d10b2e754b8d322dd8 |
| displays[2].displayHash | sha256:5cf918ab32731b85dcf031052e201c763ba0972d98f2badb1c8d7a216b812c44 |
| displays[2].data[0].dataset | adsl |
| displays[2].data[0].hash | sha256:f9a1c3605cb277363fba0add4c4228df6a288685586575be159718696c582107 |
| displays[2].data[0].n_row | 254 |
| displays[2].data[0].n_col | 60 |
| displays[2].data[0].source_pkg | pharmaverseadam |
| displays[2].data[0].source_version | 1.1.0 |
| displays[2].data[1].dataset | adex |
| displays[2].data[1].hash | sha256:e89d24c9364ba5a20a49a86de8428a8e4d8b35899b4d154ff83f89645c733f5f |
| displays[2].data[1].n_row | 6315 |
| displays[2].data[1].n_col | 92 |
| displays[2].data[1].source_pkg | pharmaverseadam |
| displays[2].data[1].source_version | 1.1.0 |
| displays[2].environment.r | 4.3.3 |
| displays[2].environment.os | Darwin 23.6.0 |
| displays[2].environment.packages.cards | 0.6.1 |
| displays[2].environment.packages.cardx | 0.2.5 |
| displays[2].environment.packages.gtsummary | 2.3.0 |
| displays[2].environment.packages.gt | 1.0.0 |
| displays[2].environment.packages.dplyr | 1.1.4 |
| displays[2].environment.packages.pharmaverseadam | 1.1.0 |
| displays[2].environment.packages.jsonlite | 2.0.0 |
| displays[2].environment.packages.yaml | 2.3.10 |
| displays[2].environment.packages.digest | 0.6.37 |
| displays[2].source | outputs |
| displays[2].ardPath | outputs/t-exposure/v002/ard.json |
| displays[2].fixture | false |
| displays[3].slug | t-ae-overview |
| displays[3].number | 14.3.1.2 |
| displays[3].title | Overview of Treatment-Emergent Adverse Events |
| displays[3].created | 2026-07-27T03:23:34Z |
| displays[3].specHash | sha256:6b0ba696f8cb4abffc3741982f36bb3bc4a47a68d84e0da1cb5cbf210c19a90a |
| displays[3].displayHash | sha256:04520444415a62c1f632d67d37a67e33c3f2a9dd4c9b7006cae32eb21bcdf2bb |
| displays[3].data[0].dataset | adsl |
| displays[3].data[0].hash | sha256:f9a1c3605cb277363fba0add4c4228df6a288685586575be159718696c582107 |
| displays[3].data[0].n_row | 254 |
| displays[3].data[0].n_col | 60 |
| displays[3].data[0].source_pkg | pharmaverseadam |
| displays[3].data[0].source_version | 1.1.0 |
| displays[3].data[1].dataset | adae |
| displays[3].data[1].hash | sha256:7d4237afdbf934742091e6b7e0a756fcba6a0e79fc9f35b578f86574baf8f7d4 |
| displays[3].data[1].n_row | 1191 |
| displays[3].data[1].n_col | 105 |
| displays[3].data[1].source_pkg | pharmaverseadam |
| displays[3].data[1].source_version | 1.1.0 |
| displays[3].environment.r | 4.3.3 |
| displays[3].environment.os | Darwin 23.6.0 |
| displays[3].environment.packages.cards | 0.6.1 |
| displays[3].environment.packages.cardx | 0.2.5 |
| displays[3].environment.packages.gtsummary | 2.3.0 |
| displays[3].environment.packages.gt | 1.0.0 |
| displays[3].environment.packages.dplyr | 1.1.4 |
| displays[3].environment.packages.pharmaverseadam | 1.1.0 |
| displays[3].environment.packages.jsonlite | 2.0.0 |
| displays[3].environment.packages.yaml | 2.3.10 |
| displays[3].environment.packages.digest | 0.6.37 |
| displays[3].source | outputs |
| displays[3].ardPath | outputs/t-ae-overview/v002/ard.json |
| displays[3].fixture | false |
| displays[4].slug | t-ae-common |
| displays[4].number | 14.3.1.3 |
| displays[4].title | Treatment-Emergent Adverse Events by System Organ Class and Preferred Term |
| displays[4].created | 2026-07-27T03:23:32Z |
| displays[4].specHash | sha256:a45e3a1f2586dd0bffa2e2f660162d958e9ae20f6eb87df9511b7d49b5c74203 |
| displays[4].displayHash | sha256:c749510c8b10f6e4f45381eacb9d85aca93d56e62e9b5f2b71f41d050d112433 |
| displays[4].data[0].dataset | adsl |
| displays[4].data[0].hash | sha256:f9a1c3605cb277363fba0add4c4228df6a288685586575be159718696c582107 |
| displays[4].data[0].n_row | 254 |
| displays[4].data[0].n_col | 60 |
| displays[4].data[0].source_pkg | pharmaverseadam |
| displays[4].data[0].source_version | 1.1.0 |
| displays[4].data[1].dataset | adae |
| displays[4].data[1].hash | sha256:7d4237afdbf934742091e6b7e0a756fcba6a0e79fc9f35b578f86574baf8f7d4 |
| displays[4].data[1].n_row | 1191 |
| displays[4].data[1].n_col | 105 |
| displays[4].data[1].source_pkg | pharmaverseadam |
| displays[4].data[1].source_version | 1.1.0 |
| displays[4].environment.r | 4.3.3 |
| displays[4].environment.os | Darwin 23.6.0 |
| displays[4].environment.packages.cards | 0.6.1 |
| displays[4].environment.packages.cardx | 0.2.5 |
| displays[4].environment.packages.gtsummary | 2.3.0 |
| displays[4].environment.packages.gt | 1.0.0 |
| displays[4].environment.packages.dplyr | 1.1.4 |
| displays[4].environment.packages.pharmaverseadam | 1.1.0 |
| displays[4].environment.packages.jsonlite | 2.0.0 |
| displays[4].environment.packages.yaml | 2.3.10 |
| displays[4].environment.packages.digest | 0.6.37 |
| displays[4].source | outputs |
| displays[4].ardPath | outputs/t-ae-common/v003/ard.json |
| displays[4].fixture | false |
| displays[5].slug | l-ae-serious |
| displays[5].number | 14.3.2.1 |
| displays[5].title | Listing of Serious Adverse Events |
| displays[5].created | 2026-07-27T03:23:31Z |
| displays[5].specHash | sha256:a046fb1cdc11ed10d586284efeb97e30ab743f4ad394869bd83ae1bfb401d140 |
| displays[5].displayHash | sha256:b865356eb33a50fb5cabae395251d60df06c7607485231ce1ae9516804af6523 |
| displays[5].data[0].dataset | adsl |
| displays[5].data[0].hash | sha256:f9a1c3605cb277363fba0add4c4228df6a288685586575be159718696c582107 |
| displays[5].data[0].n_row | 254 |
| displays[5].data[0].n_col | 60 |
| displays[5].data[0].source_pkg | pharmaverseadam |
| displays[5].data[0].source_version | 1.1.0 |
| displays[5].data[1].dataset | adae |
| displays[5].data[1].hash | sha256:7d4237afdbf934742091e6b7e0a756fcba6a0e79fc9f35b578f86574baf8f7d4 |
| displays[5].data[1].n_row | 1191 |
| displays[5].data[1].n_col | 105 |
| displays[5].data[1].source_pkg | pharmaverseadam |
| displays[5].data[1].source_version | 1.1.0 |
| displays[5].environment.r | 4.3.3 |
| displays[5].environment.os | Darwin 23.6.0 |
| displays[5].environment.packages.cards | 0.6.1 |
| displays[5].environment.packages.cardx | 0.2.5 |
| displays[5].environment.packages.gtsummary | 2.3.0 |
| displays[5].environment.packages.gt | 1.0.0 |
| displays[5].environment.packages.dplyr | 1.1.4 |
| displays[5].environment.packages.pharmaverseadam | 1.1.0 |
| displays[5].environment.packages.jsonlite | 2.0.0 |
| displays[5].environment.packages.yaml | 2.3.10 |
| displays[5].environment.packages.digest | 0.6.37 |
| displays[5].source | outputs |
| displays[5].ardPath | outputs/l-ae-serious/v002/ard.json |
| displays[5].fixture | false |
16.1.10 Documentation of Inter-laboratory Standardisation Methods and Quality Assurance Procedures if Used
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16.1.11 Publications Based on the Study
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16.1.12 Important Publications Referenced in the Report
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16.2 Patient Data Listings
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16.2.1 Discontinued Patients
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16.2.2 Protocol Deviations
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16.2.3 Patients Excluded from the Efficacy Analysis
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16.2.4 Demographic Data
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16.2.5 Compliance and/or Drug Concentration Data (if available)
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16.2.6 Individual Efficacy Response Data
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16.2.7 Adverse Event Listings (each patient)
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16.2.8 Listing of Individual Laboratory Measurements by Patient, When Required by Regulatory Authorities
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16.3 Case Report Forms
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16.3.1 CRFs for Deaths, Other Serious Adverse Events and Withdrawals for AE
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16.3.2 Other CRFs Submitted
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16.4 Individual Patient Data Listings (US Archival Listings)
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