Safety and Efficacy of the Xanomeline Transdermal Therapeutic System (TTS) in Patients with Mild to Moderate Alzheimer's Disease

Source
Publicly Available
Added
16 Jun 2026
Contributor
System
Produced by
CDISC USDM E2J 0.62.0
Phase II Trial Interventional Study v2 USDM v4.0
Sponsor
Eli Lilly
Protocol ID
H2Q-MC-LZZT
ClinicalTrials.gov
NCT12345678

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Synopsis

The discontinuation rate associated with this oral dosing regimen was 58.6% in previous studies, and alternative clinical strategies have been sought to improve tolerance for the compound. To that end, development of a Transdermal Therapeutic System (TTS) has been initiated.

Study

Study type
Interventional Study
Phase
Phase II Trial
Therapeutic area
Mild to Moderate Alzheimer's Disease · Alzheimer's disease
Indication
Indication 1 · Indication 2
Protocol version
2

Design

Design
Interventional
Model
Parallel Study
Blinding
Double Blind Study
Intent
Treatment Study
Sub-type
Efficacy Study · Safety Study · Pharmacokinetic Study
Arms
3
Epochs
5

Participants

Population
Patients with Probable Mild to Moderate Alzheimer's Disease
Planned enrolment
300
Planned completion
300
Age
50 Year to 100 Year
Healthy participants
Patients only
Cohorts
POP2 · POP3

Key dates

Design Approval
01 Jun 2006

Objectives and endpoints

Trial Primary
To determine if there is a statistically significant relationship (overall Type 1 erroralpha=0.05) between the change in both the ADAS-Cog (11) and CIBIC+ scores, and drug dose (0, 50 cm2 [54 mg], and 75 cm2 [81 mg]).
  • Primary
    Alzheimer's Disease Assessment Scale - Cognitive Subscale, total of 11 items [ADAS-Cog (11)] at Week 24
  • Primary
    Video-referenced Clinician’s Interview-based Impression of Change (CIBIC+) at Week 24
Trial Secondary
To document the safety profile of the xanomeline TTS.
  • Secondary
    Adverse events
  • Secondary
    Vital signs (weight, standing and supine blood pressure, heart rate)
  • Secondary
    Laboratory evaluations (Change from Baseline)
Trial Secondary
To assess the dose-dependent improvement in behavior. Improved scores on the Revised Neuropsychiatric Inventory (NPI-X) will indicate improvement in these areas.
  • Secondary
    Alzheimer's Disease Assessment Scale - Cognitive Subscale, total of 11 items [ADAS-Cog (11)] at Weeks 8 and 16
  • Secondary
    Video-referenced Clinician’s Interview-based Impression of Change (CIBIC+) at Weeks 8 and 16
  • Secondary
    Mean Revised Neuropsychiatric Inventory (NPI-X) from Week 4 to Week 24

Eligibility

Inclusion 3

  1. 1
    Subjects shall be between 50 Year and 100 Year
  2. 2

    usdm:tag name="StudyPopulation"/> as defined by the NINCDS and the ADRDA guidelines (Attachment LZZT.7)

  3. 3

    usdm:tag name="Activity1"/> score of 10 to 23

Exclusion 1

  1. 9
    Persons who have previously completed or withdrawn from this study or any other study investigating xanomeline TTS or the oral formulation of xanomeline.

No order is declared for these criteria, which USDM permits. Grouped by inclusion and exclusion, then by criterion number.

Study design

Arm Screening Screening Epoch Treatment One Treatment Epoch Treatment Two Treatment Epoch Treatment Three Treatment Epoch Follow Up Follow-Up Epoch
Placebo Placebo Control Arm Screening Placebo Placebo Placebo Follow up
Xanomeline Low Dose Active Comparator Arm Screening Low Low Low Follow up
Xanomeline High Dose Active Comparator Arm Screening High - Start High - Middle High - End Follow up

When each stage starts and ends

Screening
StartsInformed consent
EndsCompletion of all screening activities and no more than 2 weeks from informed consent
Placebo
StartsAdministration of first dose
Follow up
StartsEnd of last scheduled visit on study (including early termination)
EndsCompletion of all specified followup activities (which vary on a patient-by-patient basis)
Low
StartsAdministration of first dose
High - Start
StartsRandomized
High - Middle
StartsAdministration of first dose (from patches supplied at Visit 4)
High - End
StartsAdministration of first dose (from patches supplied at Visit 12)

Interventions

Int Label 1

Experimental Intervention Pharmacologic Substance A

Int Desc 1

Admin 1 12 Milligram · Dental Route of Administration · Ten Days Per Month · 14 Percentage

Int Label 2

Placebo Pharmacologic Substance A

Int Desc 2

Admin 2 12 Milligram · Dental Route of Administration · Ten Days Per Month · 14 Percentage

New infusion pump

Medical device Centrally Sourced

Infusion pump

Hardware 1.0 Software 1.0

Injection

Medical device Locally Sourced
Hardware 2.1 Software 3.6

Schedule of Activities

16 visits 30 activities Planned duration: It will be approximately 36 weeks. Entry: Potential subject identified

Schedule of Activities — 16 visits

Activity Screening Treatment One Treatment Two Treatment Three Follow Up
Visit Screen One Screening 1 Screen Two Screening 2 Dose Baseline Week 2 Week 4 Week 6 Week 8 Week NPI Week 8 Week 12 Week 12 NPI Week 12 Week 16 Week 16 NPI Week 16 Week 20 Week 20 NPI Week 20 Week 24 Week 26
Study day Day -14 Day -2 Day 1 ◆ Day 15 Day 29 Day 43 Day 57 Day 71 Day 85 Day 99 Day 113 Day 127 Day 141 Day 155 Day 169 Day 183
Window -4..0 hours -3..3 days -3..3 days -3..3 days -3..3 days -4..4 days -4..4 days -4..4 days -4..4 days -3..3 days
Informed consent
Inclusion/exclusion criteria
Patient number assigned
Demographics
Hachinski
MMSE
Physical examination
Medical history
Habits
Chest X-ray
Apo E genotyping
Patient randomised
Vital Signs and Temperature has its own schedule
Ambulatory ECG placed
Ambulatory ECG removed
ECG
Placebo TTS test
CT scan
Concomitant medications
Hematology
Chemistry
Uninalysis
Plasma Specimen (Xanomeline)
Hemoglobin A1C
Study drug record , Medications dispensed, Medications returned
TTS Acceptability Survey
ADAS-Cog
CIBIC+
DAD
NPI-X

◆ marks the fixed reference the other visits are counted from.

Other schedules in this design

  • Adverse Event Timeline 1 visit · 1 activity Entered when: Subject suffers an adverse event
  • Early Termination Timeline 1 visit · 15 activities Entered when: Subject terminates the study early
  • Vital Sign Blood Pressure Timeline 4 visits · 4 activities Entered when: Automatic execution

Separate schedules, not part of the visit schedule above.

Protocol document

The full text of the 2 protocol documents in this file.

Protocol_Document_CDISC PILOT - LZZT

Sponsor Confidentiality Statement:

Full Title:

Safety and Efficacy of the Xanomeline Transdermal Therapeutic System (TTS) in Patients with Mild to Moderate Alzheimer's Disease

Trial Acronym:

H2Q-MC-LZZT

Protocol Identifier:

H2Q-MC-LZZT

Original Protocol:

Version Number:

2

Version Date:

2006-06-01

Amendment Identifier:

1

Amendment Scope:

Global

Compound Codes(s):

Compound Name(s):

Trial Phase:

Phase II Trial

Short Title:

Xanomeline (LY246708)

Sponsor Name and Address:

Eli Lilly, Lilly Corporate Ctr, Indianapolis, , IN, 4628, United States of America

Regulatory Agency Identifier Number(s):

NCT12345678

Spondor Approval Date:

2006-07-01

1 PROTOCOL SUMMARY

No content for this section.

1.1 Protocol Synopsis

No content for this section.

1.2 Trial Schema

No content for this section.

1.3 Schedule of Activities

Timeline: Vital Sign Blood Pressure Timeline, Automatic execution

BP Anchor

BP while Supine

BP Stand Up

BP while standing

-2..0 min

Supine for 5 minutes

X

Blood pressure supine

X

Stand for 3 minutes

X

Blood pressure standing

X

2 INTRODUCTION

No content for this section.

2.1 Purpose of Trial

No content for this section.

2.2 Summary of Benefits and Risks

No content for this section.

3 TRIAL OBJECTIVES, ENDPOINTS AND ESTIMANDS

No content for this section.

3.1 Primary Objectives

To determine if there is a statistically significant relationship (overall Type 1 erroralpha=0.05) between the change in both the ADAS-Cog (11) and CIBIC+ scores, and drug dose (0, 50 cm2 [54 mg], and 75 cm2 [81 mg]).

Alzheimer's Disease Assessment Scale - Cognitive Subscale, total of 11 items [ADAS-Cog (11)] at Week 24

Video-referenced Clinician’s Interview-based Impression of Change (CIBIC+) at Week 24

To document the safety profile of the xanomeline TTS.

Adverse events

Vital signs (weight, standing and supine blood pressure, heart rate)

Laboratory evaluations (Change from Baseline)

To assess the dose-dependent improvement in behavior. Improved scores on the Revised Neuropsychiatric Inventory (NPI-X) will indicate improvement in these areas.

Alzheimer's Disease Assessment Scale - Cognitive Subscale, total of 11 items [ADAS-Cog (11)] at Weeks 8 and 16

Video-referenced Clinician’s Interview-based Impression of Change (CIBIC+) at Weeks 8 and 16

Mean Revised Neuropsychiatric Inventory (NPI-X) from Week 4 to Week 24

4 TRIAL DESIGN

No content for this section.

4.1 Description of Trial Design
Temperature
4.1.1 Participant Input into Design

No content for this section.

4.2 Rationale for Trial Design

Previous studies of the oral formulation have shown that xanomeline tartrate may improve behavior and cognition. Effects on behavior are manifest within 2 to 4 weeks of initiation of treatment. The same studies have shown that 8 to 12 weeks are required to demonstrate effects on cognition and clinical global assessment. This study is intended to determine the acute and chronic effects of the TTS formulation in AD; for that reason, the study is of 26 weeks duration. Dosage specification has been made on the basis of tolerance to the xanomeline TTS in a clinical pharmacology study (H2Q-EW-LKAA), and target plasma levels as determined in studies of the oral formulation of xanomeline (H2Q-MC-LZZA).

4.2.1 Rationale for Comparator

The parallel dosing regimen maximizes the ability to make direct comparisons between the treatment groups. The use of placebo allows for a blinded, thus minimally biased, study. The placebo treatment group is a comparator group for efficacy and safety assessment.

Two interim analyses are planned for this study. The first interim analysis will occur when 50% of the patients have completed Visit 8 (8 weeks). If required, the second interim analysis will occur when 50% of the patients have completed Visit 12 (24 weeks).

4.2.2 Rationale for Adaptive or Novel Trial Design

No content for this section.

4.2.3 Other Trial Design Considerations

No content for this section.

4.3 Access to Trial Intervention After End of Trial

No content for this section.

4.4 Start of Trial and End of Trial

No content for this section.

5 TRIAL POPULATION

No content for this section.

5.1 Selection of Trial Population

For Lilly studies, the following definitions are used:

Screen

Screening is the act of determining if an individual meets minimum requirements to become part of a pool of potential candidates for participation in a clinical study.

In this study, screening will include asking the candidate preliminary questions (such as age and general health status) and conducting invasive or diagnostic procedures and/or tests (for example, diagnostic psychological tests, x-rays, blood draws). Patients will sign the consent at their screening visit, thereby consenting to undergo the screening procedures and to participate in the study if they qualify.

To enter

Patients entered into the study are those from whom informed consent for the study has been obtained. Adverse events will be reported for each patient who has entered the study, even if the patient is never assigned to a treatment group (enrolled).

To enroll

Patients who are enrolled in the study are those who have been assigned to a treatment group. Patients who are entered into the study but fail to meet criteria specified in the protocol for treatment assignment will not be enrolled in the study.

At Visit 1, patients who meet the enrollment criteria of Mini-Mental State Examination (MMSE) score of 10 to 23 (Attachment LZZT.6), Hachinski Ischemia Score ≤4 (Attachment LZZT.8), a physical exam, safety labs, ECG, and urinalysis, will proceed to Visit 2 and Visit 3. At Visit 3, patients whose CNS imaging and other pending labs from Visit 1 satisfy the inclusion criteria (Section 3.4.2.1) will be enrolled in the study. Approximately 300 patients with a diagnosis of probable mild to moderate AD will be enrolled in the study.

5.2 Rationale for Trial Population

No content for this section.

5.3 Inclusion Criteria

Patients may be included in the study only if they meet all the following criteria:

1

Subjects shall be between 50 Year and 100 Year

2

usdm:tag name="StudyPopulation"/> as defined by the NINCDS and the ADRDA guidelines (Attachment LZZT.7)

3

usdm:tag name="Activity1"/> score of 10 to 23

5.4 Exclusion Criteria

Patients may be excluded in the study for any of the following reasons:

9

Persons who have previously completed or withdrawn from this study or any other study investigating xanomeline TTS or the oral formulation of xanomeline.

5.5 Lifestyle Considerations

No content for this section.

5.5.1 Meals and Dietary Restrictions

No content for this section.

5.5.2 Caffeine, Alcohol, Tobacco, and Other Habits

Not applicable

5.5.3 Physical Activity

No content for this section.

5.5.4 Other Activity

No content for this section.

5.6 Screen Failures

No content for this section.

6 TRIAL INTERVENTION AND CONCOMITANT THERAPY

No content for this section.

6.1 Description of Trial Intervention

No content for this section.

6.2 Rationale for Trial Intervention

No content for this section.

6.3 Dosing and Administration

No content for this section.

6.3.1 Trial Intervention Dose Modification

No content for this section.

6.4 Treatment of Overdose

No content for this section.

6.5 Preparation, Handling, Storage and Accountability

No content for this section.

6.5.1 Preparation of Trial Intervention

No content for this section.

6.5.2 Handling and Storage of Trial Intervention

No content for this section.

6.5.3 Accountability of Trial Intervention

No content for this section.

6.6 Participant Assignment, Randomisation and Blinding

No content for this section.

6.6.1 Participant Assignment

No content for this section.

6.6.2 Randomisation

No content for this section.

6.6.3 Blinding and Unblinding

The study will be double-blind. To further preserve the blinding of the study, only a minimum number of Lilly and CRO personnel will see the randomization table and codes before the study is complete.

Emergency codes generated by a computer drug-labeling system will be available to the investigator. These codes, which reveal the patients treatment group, may be opened during the study only if the choice of follow-up treatment depends on the patient’s therapy assignment.

The investigator should make every effort to contact the clinical research physician prior to unblinding a patient’s therapy assignment. If a patient’s therapy assignment is unblinded, Lilly must be notified immediately by telephone. After the study, the investigator must return all sealed and any opened codes.

6.7 Trial Intervention Compliance

No content for this section.

6.8 Concomitant Therapy

No content for this section.

6.8.1 Prohibited Concomitant Therapy

No content for this section.

6.8.2 Permitted Concomitant Therapy

No content for this section.

6.8.3 Rescue Therapy

No content for this section.

6.8.4 Other Therapy

No content for this section.

7 DISCONTINUATION OF TRIAL INTERVENTION AND PARTICIPANT WITHDRAWAL FROM TRIAL

No content for this section.

7.1 Discontinuation of Trial Intervention

No content for this section.

7.1.1 Criteria for Permanent Discontinuation of Trial Intervention

No content for this section.

7.1.2 Temporary Discontinuation or Interruption of Trial Intervention

No content for this section.

7.1.3 Rechallenge

No content for this section.

7.2 Participant Withdrawal from the Trial

No content for this section.

7.3 Lost to Follow-Up

No content for this section.

7.4 Trial Stopping Rules

No content for this section.

8 TRIAL ASSESSMENTS AND PROCEDURES

No content for this section.

8.1 Screening/Baseline Assessments and Procedures

No content for this section.

8.2 Efficacy Assessments and Procedures

No content for this section.

8.3 Safety Assessments and Procedures

No content for this section.

8.3.1 Physical Examination

No content for this section.

8.3.2 Vital Signs

No content for this section.

8.3.3 Electrocardiograms

No content for this section.

8.3.4 Clinical Laboratory Assessments

No content for this section.

8.3.5 Suicidal Ideation and Behaviour Risk Monitoring

No content for this section.

8.4 Adverse Events and Serious Adverse Events

No content for this section.

8.4.1 Definitions of AE and SAE

No content for this section.

8.4.2 Time Period and Frequency for Collecting AE and SAE Information

No content for this section.

8.4.3 Identifying AEs and SAEs

No content for this section.

8.4.4 Recording of AEs and SAEs

No content for this section.

8.4.5 Follow-up of AEs and SAEs

No content for this section.

8.4.6 Reporting of SAEs

No content for this section.

8.4.7 Regulatory Reporting Requirements for SAEs

No content for this section.

8.4.8 Serious and Unexpected Adverse Reaction Reporting

No content for this section.

8.4.9 Adverse Events of Special Interest

No content for this section.

8.4.10 Disease-related Events or Outcomes Not Qualifying as AEs or SAEs

No content for this section.

8.5 Pregnancy and Postpartum Information

No content for this section.

8.5.1 Participants Who Become Pregnant During the Trial

No content for this section.

8.5.2 Participants Whose Partners Become Pregnant

No content for this section.

8.6 Medical Device Product Complaints for Drug/Device Combination Products

No content for this section.

8.6.1 Definition of Medical Device Product Complaints

No content for this section.

8.6.2 Recording of Medical Device Product Complaints

No content for this section.

8.6.3 Time Period and Frequency for Collecting Medical Device Product Complaints .

No content for this section.

8.6.4 Follow-Up of Medical Device Product Complaints

No content for this section.

8.6.5 Regulatory Reporting Requirements for Medical Device Product Complaints

No content for this section.

8.7 Pharmacokinetics

No content for this section.

8.8 Genetics

No content for this section.

8.9 Biomarkers

No content for this section.

8.10 Immunogenicity Assessments

No content for this section.

8.10.1 Medical Resource Utilisation and Health Economics

No content for this section.

9 STATISTICAL CONSIDERATIONS

No content for this section.

9.1 Analysis Sets

No content for this section.

9.2 Analyses Supporting Primary Objective(s)

No content for this section.

9.2.1 Statistical Model, Hypothesis, and Method of Analysis

No content for this section.

9.2.2 Handling of Intercurrent Events of Primary Estimand(s)

No content for this section.

9.2.3 Handling of Missing Data

No content for this section.

9.2.4 Sensitivity Analysis

No content for this section.

9.2.5 Supplementary Analysis

No content for this section.

9.3 Analysis Supporting Secondary Objective(s)

No content for this section.

9.4 Analysis of Exploratory Objective(s)

No content for this section.

9.5 Safety Analyses

No content for this section.

9.6 Other Analyses

No content for this section.

9.7 Interim Analyses

No content for this section.

9.8 Sample Size Determination

No content for this section.

9.9 Protocol Deviations

No content for this section.

10 GENERAL CONSIDERATIONS: REGULATORY, ETHICAL, AND TRIAL OVERSIGHT

No content for this section.

10.1 Regulatory and Ethical Considerations

No content for this section.

10.2 Committees

No content for this section.

10.3 Informed Consent Process

No content for this section.

10.4 Data Protection

No content for this section.

10.5 Early Site Closure or Trial Termination

No content for this section.

11 GENERAL CONSIDERATIONS: RISK MANAGEMENT AND QUALITY ASSURANCE

No content for this section.

11.1 Quality Tolerance Limits

No content for this section.

11.2 Data Quality Assurance

No content for this section.

11.3 Source Data

No content for this section.

12 APPENDIX: ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS - DEFINITIONS, SEVERITY, AND CAUSALITY

No content for this section.

12.1 Further Details and Clarifications on the AE Definition

No content for this section.

12.2 Further Details and Clarifications on the SAE Definition

No content for this section.

12.3 Severity

No content for this section.

12.4 Causality

No content for this section.

13 APPENDIX: DEFINITIONS AND SUPPORTING OPERATIONAL DETAILS

No content for this section.

13.1 Contraception and Pregnancy Testing

No content for this section.

13.1.1 Definitions Related to Childbearing Potential

No content for this section.

13.1.2 Contraception

No content for this section.

13.1.3 Pregnancy Testing

No content for this section.

13.2 Clinical Laboratory Tests

No content for this section.

13.3 Country/Region-Specific Differences

No content for this section.

13.4 Prior Protocol Amendments

No content for this section.

14 APPENDIX: GLOSSARY OF TERMS

No content for this section.

15 APPENDIX: REFERENCES

No content for this section.

Protocol_Document_CDISC PILOT - LZZT_2

This document declares 132 sections, none of which carry text. The outline is below.
  1. 0 TITLE PAGE —
  2. 1 PROTOCOL SUMMARY —
  3. 1.1 Protocol Synopsis —
  4. 1.2 Trial Schema —
  5. 1.3 Schedule of Activities —
  6. 2 INTRODUCTION —
  7. 2.1 Purpose of Trial —
  8. 2.2 Summary of Benefits and Risks —
  9. 3 TRIAL OBJECTIVES, ENDPOINTS AND ESTIMANDS —
  10. 3.1 Primary Objectives —
  11. 4 TRIAL DESIGN —
  12. 4.1 Description of Trial Design —
  13. 4.2 Rationale for Trial Design —
  14. 4.3 Access to Trial Intervention After End of Trial —
  15. 4.4 Start of Trial and End of Trial —
  16. 5 TRIAL POPULATION —
  17. 5.1 Selection of Trial Population —
  18. 5.2 Rationale for Trial Population —
  19. 5.3 Inclusion Criteria —
  20. 5.4 Exclusion Criteria —
  21. 5.5 Lifestyle Considerations —
  22. 5.6 Screen Failures —
  23. 6 TRIAL INTERVENTION AND CONCOMITANT THERAPY —
  24. 6.1 Description of Trial Intervention —
  25. 6.2 Rationale for Trial Intervention —
  26. 6.3 Dosing and Administration —
  27. 6.4 Treatment of Overdose —
  28. 6.5 Preparation, Handling, Storage and Accountability —
  29. 6.6 Participant Assignment, Randomisation and Blinding —
  30. 6.7 Trial Intervention Compliance —
  31. 6.8 Concomitant Therapy —
  32. 7 DISCONTINUATION OF TRIAL INTERVENTION AND PARTICIPANT WITHDRAWAL FROM TRIAL —
  33. 7.1 Discontinuation of Trial Intervention —
  34. 7.2 Participant Withdrawal from the Trial —
  35. 7.3 Lost to Follow-Up —
  36. 7.4 Trial Stopping Rules —
  37. 8 TRIAL ASSESSMENTS AND PROCEDURES —
  38. 8.1 Screening/Baseline Assessments and Procedures —
  39. 8.2 Efficacy Assessments and Procedures —
  40. 8.3 Safety Assessments and Procedures —
  41. 8.4 Adverse Events and Serious Adverse Events —
  42. 8.5 Pregnancy and Postpartum Information —
  43. 8.6 Medical Device Product Complaints for Drug/Device Combination Products —
  44. 8.7 Pharmacokinetics —
  45. 8.8 Genetics —
  46. 8.9 Biomarkers —
  47. 8.10 Immunogenicity Assessments —
  48. 9 STATISTICAL CONSIDERATIONS —
  49. 9.1 Analysis Sets —
  50. 9.2 Analyses Supporting Primary Objective(s) —
  51. 9.3 Analysis Supporting Secondary Objective(s) —
  52. 9.4 Analysis of Exploratory Objective(s) —
  53. 9.5 Safety Analyses —
  54. 9.6 Other Analyses —
  55. 9.7 Interim Analyses —
  56. 9.8 Sample Size Determination —
  57. 9.9 Protocol Deviations —
  58. 10 GENERAL CONSIDERATIONS: REGULATORY, ETHICAL, AND TRIAL OVERSIGHT —
  59. 10.1 Regulatory and Ethical Considerations —
  60. 10.2 Committees —
  61. 10.3 Informed Consent Process —
  62. 10.4 Data Protection —
  63. 10.5 Early Site Closure or Trial Termination —
  64. 11 GENERAL CONSIDERATIONS: RISK MANAGEMENT AND QUALITY ASSURANCE —
  65. 11.1 Quality Tolerance Limits —
  66. 11.2 Data Quality Assurance —
  67. 11.3 Source Data —
  68. 12 APPENDIX: ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS - DEFINITIONS, SEVERITY, AND CAUSALITY —
  69. 12.1 Further Details and Clarifications on the AE Definition —
  70. 12.2 Further Details and Clarifications on the SAE Definition —
  71. 12.3 Severity —
  72. 12.4 Causality —
  73. 13 APPENDIX: DEFINITIONS AND SUPPORTING OPERATIONAL DETAILS —
  74. 13.1 Contraception and Pregnancy Testing —
  75. 13.2 Clinical Laboratory Tests —
  76. 13.3 Country/Region-Specific Differences —
  77. 13.4 Prior Protocol Amendments —
  78. 14 APPENDIX: GLOSSARY OF TERMS —
  79. 15 APPENDIX: REFERENCES —
Conformance CDISC CORE CDISC Open Rules Engine No issues reported 207 rules 193 passed 14 not evaluated Engine 0.15.0 USDM v4.0 rules Run 16 Jun 2026

CDISC CORE

CDISC Open Rules Engine
No issues reported 207 rules 193 passed 14 not evaluated Engine 0.15.0 USDM v4.0 rules Run 16 Jun 2026
JSON report Excel report

Not evaluated 14

12 skipped · 2 engine errors 14 rules
  • DDF00114 Engine error The specified context of the condition is not a valid instance of either the Activity or ScheduledActivityInstance class (the value of the condition's contextIds attribute either matches the id of an instance that is not an Activity or ScheduledActivityInstance, or it does not match the id of any class instance). Failed to execute rule operation. Operation: record_count, Target: None, Domain: Condition, Error: Failed to execute rule operation. Domain Condition does not exist. Operation: record_count, Target: None, Core ID: CORE-000878
  • DDF00141 Engine error The planned sex is not specified using the Sex of Participants (C66732) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive), and/or neither code nor decode is found in the codelist. Failed to execute rule operation. Operation: codelist_extensible, Target: None, Domain: StudyDesignPopulation, Error: You are trying to merge on object and float64 columns for key 'codeSystemVersion'. If you wish to proceed you should use pd.concat
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  • DDF00183 Skipped The reference identifier type is not specified according to the extensible reference identifier type (C215478) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
  • DDF00199 Skipped The study impact type is not specified according to the extensible study amendment impact type (C215481) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
  • DDF00207 Skipped The medical device identifier type is not specified according to the extensible medical device identifier type (C215484) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
  • DDF00223 Skipped The study design's observational model is not specified according to the extensible Observational Study Model (C127259) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
  • DDF00224 Skipped The observational study design's time perspective is not specified according to the extensible Observational Study Time Perspective (C127261) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
  • DDF00225 Skipped The observational study design's sampling method is not specified according to the extensible Observational Study Sampling Method (C127260) SDTM codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).
  • DDF00226 Skipped The observational study design's sub type is not specified according to the extensible observational study design subtype (C215486) DDF codelist - codeSystem is not "http://www.cdisc.org", codeSystemVersion is not a valid terminology package date, and/or the code or decode (either as preferred term or as submission value) is found in the codelist (case insensitive) but the corresponding decode or code does not match the codelist value (case sensitive).

This protocol was contributed by a third party and has not been verified. Provided for informational and standards-development purposes only — see the Disclaimer & Terms of Use.