Clinical Trial Results:
A phase II randomised, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of orally administered BI 409306 during a 28-week treatment period as adjunctive therapy to antipsychotic treatment for the prevention of relapse in patients with schizophrenia
Summary
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EudraCT number |
2017-002369-23 |
Trial protocol |
ES |
Global end of trial date |
31 Mar 2021
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Results information
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Results version number |
v1 |
This version publication date |
25 Mar 2022
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First version publication date |
25 Mar 2022
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1289-0049
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03351244 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Boehringer Ingelheim
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Sponsor organisation address |
Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
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Public contact |
Boehringer Ingelheim Call Center, Boehringer Ingelheim, +1 8002430127, clintriage.rdg@boehringer-ingelheim.com
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Scientific contact |
Boehringer Ingelheim Call Center, Boehringer Ingelheim, +1 18002430127, clintriage.rdg@boehringer-ingelheim.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Mar 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2021
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The objective of the trial was to investigate the efficacy, safety, and tolerability of BI 409306 25 mg and 50 mg once daily compared with placebo given for 28 weeks in patients with schizophrenia on antipsychotic treatment. The trial was designed to show superiority of BI 409306 over placebo in preventing relapse of schizophrenia symptoms.
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Dec 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 353
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Country: Number of subjects enrolled |
Japan: 66
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Country: Number of subjects enrolled |
Canada: 25
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Country: Number of subjects enrolled |
France: 18
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Country: Number of subjects enrolled |
Korea, Republic of: 5
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Country: Number of subjects enrolled |
Taiwan: 2
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Country: Number of subjects enrolled |
Spain: 1
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Worldwide total number of subjects |
470
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EEA total number of subjects |
19
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
470
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This Phase II trial aimed to evaluate the impact of 28-week treatment with BI 409306 (added to standard antipsychotic medication) compared with placebo on preventing relapse in patients with schizophrenia. | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. | ||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | ||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BI 409306 25 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
1 film-coated tablet of 25 milligrams (mg) of BI 409306 plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7. Taper period: 2 tablets of 10 mg BI 409306 and 2 tablets of placebo q.d. on Day 1 of the taper period; 2 tablets of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 2-3 of taper period; 1 tablet of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
BI 409306
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 film-coated tablet of 25 milligrams (mg) of BI 409306 plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7. Taper period: 2 tablets of 10 mg BI 409306 and 2 tablets of placebo q.d. on Day 1 of the taper period; 2 tablets of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 2-3 of taper period; 1 tablet of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period.
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Arm title
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BI 409306 50 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
1 film-coated tablet of 50 milligrams (mg) of BI 409306 plus 1 tablet of 25 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal period. Taper period: 4 tablets of 10 mg BI 409306 q.d. on Day 1 of taper period; 3 tablets of 10 mg BI 409306 q.d. on Day 2-3 of taper period; 2 tablets of 10 mg BI 409306 q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
BI 409306
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 film-coated tablet of 50 milligrams (mg) of BI 409306 plus 1 tablet of 25 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal period. Taper period: 4 tablets of 10 mg BI 409306 q.d. on Day 1 of taper period; 3 tablets of 10 mg BI 409306 q.d. on Day 2-3 of taper period; 2 tablets of 10 mg BI 409306 q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
1 film-coated tablet of 25 milligrams (mg) of matching Placebo plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Both withdrawal and taper periods: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal/taper period; 3 tablets of 10 mg placebo q.d. on Day 2-3 of withdrawal/taper period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal/taper period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal/taper period. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 film-coated tablet of 25 milligrams (mg) of matching Placebo plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Both withdrawal and taper periods: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal/taper period; 3 tablets of 10 mg placebo q.d. on Day 2-3 of withdrawal/taper period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal/taper period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal/taper period.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline characteristics are based on patients who were randomised after successfully completing the screening period and received at least one dose of the trial medication. |
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Baseline characteristics reporting groups
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Reporting group title |
BI 409306 25 mg
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Reporting group description |
1 film-coated tablet of 25 milligrams (mg) of BI 409306 plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7. Taper period: 2 tablets of 10 mg BI 409306 and 2 tablets of placebo q.d. on Day 1 of the taper period; 2 tablets of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 2-3 of taper period; 1 tablet of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BI 409306 50 mg
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Reporting group description |
1 film-coated tablet of 50 milligrams (mg) of BI 409306 plus 1 tablet of 25 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal period. Taper period: 4 tablets of 10 mg BI 409306 q.d. on Day 1 of taper period; 3 tablets of 10 mg BI 409306 q.d. on Day 2-3 of taper period; 2 tablets of 10 mg BI 409306 q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
1 film-coated tablet of 25 milligrams (mg) of matching Placebo plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Both withdrawal and taper periods: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal/taper period; 3 tablets of 10 mg placebo q.d. on Day 2-3 of withdrawal/taper period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal/taper period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal/taper period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BI 409306 25 mg
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Reporting group description |
1 film-coated tablet of 25 milligrams (mg) of BI 409306 plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7. Taper period: 2 tablets of 10 mg BI 409306 and 2 tablets of placebo q.d. on Day 1 of the taper period; 2 tablets of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 2-3 of taper period; 1 tablet of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | ||
Reporting group title |
BI 409306 50 mg
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Reporting group description |
1 film-coated tablet of 50 milligrams (mg) of BI 409306 plus 1 tablet of 25 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal period. Taper period: 4 tablets of 10 mg BI 409306 q.d. on Day 1 of taper period; 3 tablets of 10 mg BI 409306 q.d. on Day 2-3 of taper period; 2 tablets of 10 mg BI 409306 q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | ||
Reporting group title |
Placebo
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Reporting group description |
1 film-coated tablet of 25 milligrams (mg) of matching Placebo plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Both withdrawal and taper periods: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal/taper period; 3 tablets of 10 mg placebo q.d. on Day 2-3 of withdrawal/taper period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal/taper period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal/taper period. | ||
Subject analysis set title |
BI 409306 pooled
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This group included all participants who administered BI 409306 during the study.
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End point title |
Incidence rate of first relapse after 28 weeks of treatment | ||||||||||||||||||||
End point description |
The incidence rate of first relapse after 28 weeks of treatment is reported.
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
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End point type |
Primary
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End point timeframe |
28 weeks
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
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Comparison groups |
BI 409306 25 mg v Placebo
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Number of subjects included in analysis |
176
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.7735 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.097
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.585 | ||||||||||||||||||||
upper limit |
2.056 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 3 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
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Comparison groups |
Placebo v BI 409306 pooled
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Number of subjects included in analysis |
264
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.9862 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.005
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.576 | ||||||||||||||||||||
upper limit |
1.753 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 2 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
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Comparison groups |
BI 409306 50 mg v Placebo
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Number of subjects included in analysis |
175
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.7809 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
0.91
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.468 | ||||||||||||||||||||
upper limit |
1.77 |
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End point title |
Change from baseline in Positive and Negative Syndrome Scale (PANSS) positive symptoms score after 28 weeks of treatment | ||||||||||||||||||||
End point description |
Positive and Negative Syndrome Scale (PANSS): assesses the severity of psychotic symptoms and progression of disease.
The PANSS positive symptoms score is the sum of scores from 7 Items where each item has a minimum score 1 (better outcome) and maximum score 7 (worse outcome). The PANSS postive symptoms score ranges from 7 (less severe the disease) to 49 (more severe the disease).
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
Only participants with non-missing results were included in the analysis.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
At baseline and at Week 28.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Statistical analysis 4 | ||||||||||||||||||||
Statistical analysis description |
A restricted maximum likelihood-based approach using a mixed model with repeated measurements was applied. The analysis included the fixed, categorical effects of treatment at each visit, and the fixed continuous effects of baseline at each visit.
|
||||||||||||||||||||
Comparison groups |
BI 409306 25 mg v Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
138
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.5289 | ||||||||||||||||||||
Method |
Mixed model with repeated measurements | ||||||||||||||||||||
Parameter type |
Placebo-corrected adjusted mean | ||||||||||||||||||||
Point estimate |
0.38
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.809 | ||||||||||||||||||||
upper limit |
1.57 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 5 | ||||||||||||||||||||
Statistical analysis description |
A restricted maximum likelihood-based approach using a mixed model with repeated measurements was applied. The analysis included the fixed, categorical effects of treatment at each visit, and the fixed continuous effects of baseline at each visit.
|
||||||||||||||||||||
Comparison groups |
BI 409306 50 mg v Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
120
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.744 | ||||||||||||||||||||
Method |
Mixed model with repeated measurements | ||||||||||||||||||||
Parameter type |
Placebo-corrected adjusted mean | ||||||||||||||||||||
Point estimate |
0.21
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-1.055 | ||||||||||||||||||||
upper limit |
1.475 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 6 | ||||||||||||||||||||
Statistical analysis description |
A restricted maximum likelihood-based approach using a mixed model with repeated measurements was applied. The analysis included the fixed, categorical effects of treatment at each visit, and the fixed continuous effects of baseline at each visit.
|
||||||||||||||||||||
Comparison groups |
Placebo v BI 409306 pooled
|
||||||||||||||||||||
Number of subjects included in analysis |
193
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.5659 | ||||||||||||||||||||
Method |
Mixed model with repeated measurements | ||||||||||||||||||||
Parameter type |
Placebo-corrected adjusted mean | ||||||||||||||||||||
Point estimate |
0.31
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-0.745 | ||||||||||||||||||||
upper limit |
1.358 |
|
|||||||||||||||||||||
End point title |
Change from baseline in Clinical Global Impressions–Severity (CGI-S) scale score after 28 weeks of treatment | ||||||||||||||||||||
End point description |
Clinical Global Impressions-Severity (CGI-S): One-item evaluation completed by the clinician to measure the severity of psychopathology.
The CGI-S score ranges from 1 (normal) through to 7 (most severely ill). The higher the score, the worse the psychopathology.
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
Only participants with non-missing results were included in the analysis.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
At baseline and at Week 28
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Patient Global Impressions-Improvement (PGI-I) scale score after 28 weeks of treatment | ||||||||||||||||||||
End point description |
Patient Global Impressions-Improvement (PGI-I): One-item evaluation completed by the patient to assess their overall evaluation of his/her status compared to how they felt at randomisation.
The PGI-I score ranges from 1 (Very much better) through to 7 (Very much worse). The higher the score, the worse the improvement.
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
Only participants with non-missing results were included in the analysis.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
At Week 28
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Incidence rate of suicidal ideation and behaviour (assessed by Columbia Suicide Severity Rating Scale (C-SSRS)) after 28 weeks of treatment | ||||||||||||||||||||
End point description |
Columbia Suicide Severity Rating Scale (C-SSRS): suicide risk assessment. At a minimum, the interview consists of 2 screening questions related to suicidal ideation and 4 related to suicidal behavior, and may be expanded to up to 17 items in case of positive responses. Free text entries are allowed.
Suicidal behavior is collected in nominal scale as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior.
Suicidal ideation is rated on a 6-point scale from 0 (No ideation present) to 5 (Active ideation with plan and intent). A score of 4 or 5 on this scale indicates serious suicidal ideation.
The Incidence rate of suicidal ideation and behaviour (assessed by C-SSRS) after 28 weeks of treatment is reported.
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
28 weeks
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Statistical analysis 7 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
|
||||||||||||||||||||
Comparison groups |
BI 409306 25 mg v Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.9938 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.006
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.203 | ||||||||||||||||||||
upper limit |
4.989 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 8 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
|
||||||||||||||||||||
Comparison groups |
BI 409306 50 mg v Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
175
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.893 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.116
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.225 | ||||||||||||||||||||
upper limit |
5.531 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 9 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
|
||||||||||||||||||||
Comparison groups |
Placebo v BI 409306 pooled
|
||||||||||||||||||||
Number of subjects included in analysis |
264
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
|||||||||||||||||||||
P-value |
= 0.936 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
1.058
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.265 | ||||||||||||||||||||
upper limit |
4.233 |
|
|||||||||||||||||||||
End point title |
Change from baseline in Personal and Social Performance scale (PSP) score after 28 weeks of treatment | ||||||||||||||||||||
End point description |
Personal and Social Performance scale (PSP): The PSP is a 100-point, single item, clinician rated scale to assess 4 domains of social functioning (Four domains over the past month: (1) socially useful activities, (2) personal and social relationships, (3) self-care and (4) disturbing and aggressive behaviors.) in patients with schizophrenia. The PSP score is a single score ranging from 1 to 100. Higher scores represent better personal and social functioning.
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
Only participants with non-missing results were included in the analysis.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
At baseline and at Week 28
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Incidence rate of new prescription or increase in dose of an ongoing antipsychotic medication | ||||||||||||||||||||
End point description |
The incidence rate of new prescription or increase in dose of an ongoing antipsychotic medication is reported.
Full analysis set (FAS): the FAS includes all patients in the treated set with at least 1 baseline and post-baseline measurement of any type.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
28 weeks
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Statistical analysis 10 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
|
||||||||||||||||||||
Comparison groups |
BI 409306 25 mg v Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.6362 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
0.788
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.293 | ||||||||||||||||||||
upper limit |
2.118 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 12 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
|
||||||||||||||||||||
Comparison groups |
Placebo v BI 409306 pooled
|
||||||||||||||||||||
Number of subjects included in analysis |
264
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.4253 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
0.703
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.296 | ||||||||||||||||||||
upper limit |
1.671 | ||||||||||||||||||||
Statistical analysis title |
Statistical analysis 11 | ||||||||||||||||||||
Statistical analysis description |
The model included the treatment effect as the only covariate and was stratified by country.
|
||||||||||||||||||||
Comparison groups |
BI 409306 50 mg v Placebo
|
||||||||||||||||||||
Number of subjects included in analysis |
175
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||
P-value |
= 0.3782 | ||||||||||||||||||||
Method |
Regression, Cox | ||||||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||||||
Point estimate |
0.612
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.205 | ||||||||||||||||||||
upper limit |
1.826 |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All-cause mortality: From 1st dose until withdraw or end of 1-week (1W) taper period + 3W follow-up, up to 32W. Serious (non-serious) adverse events: From 1st dose until withdraw or end of 1W taper period + 1W residual effect period, up to 30W.
|
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Adverse event reporting additional description |
Treated set (TS): the TS includes all patients who were randomised and were documented to have taken at least 1 dose of trial drug.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BI 409306 25mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
1 film-coated tablet of 25 milligrams (mg) of BI 409306 plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7. Taper period: 2 tablets of 10 mg BI 409306 and 2 tablets of placebo q.d. on Day 1 of the taper period; 2 tablets of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 2-3 of taper period; 1 tablet of 10 mg BI 409306 and 1 tablet of placebo q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
1 film-coated tablet of 25 milligrams (mg) of matching Placebo plus 1 tablet of 50 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a followup period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Both withdrawal and taper periods: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal/taper period; 3 tablets of 10 mg placebo q.d. on Day 2-3 of withdrawal/taper period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal/taper period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal/taper period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BI 409306 50mg
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Reporting group description |
1 film-coated tablet of 50 milligrams (mg) of BI 409306 plus 1 tablet of 25 mg matching placebo were administered orally once daily for a treatment period of 28 weeks, followed by a withdrawal/taper period of 7 days, followed by a follow-up period of 3 weeks. Participants were randomized to either withdrawal or taper period in 1:1 ratio at the randomization of treatment groups. Withdrawal period: 4 tablets of 10 mg placebo once daily (q.d.) on Day 1 of withdrawal period; 3 tablets of 10 mg placebo q.d. on Day2-3 of withdrawal period; 2 tablets of 10mg placebo q.d. on Day 4-5 of withdrawal period; 1 tablet of 10mg placebo q.d. on Day 6-7 of withdrawal period. Taper period: 4 tablets of 10 mg BI 409306 q.d. on Day 1 of taper period; 3 tablets of 10 mg BI 409306 q.d. on Day 2-3 of taper period; 2 tablets of 10 mg BI 409306 q.d. on Day 4-5 of taper period; 1 tablet of 10 mg BI 409306 q.d. on Day 6-7 of taper period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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08 Nov 2017 |
- The key secondary endpoint, change from baseline in Positive and Negative Syndrome Scale (PANSS) positive symptoms score after 28 weeks of treatment, was added (it was a further endpoint prior to the revision). The key secondary endpoint was added to the hypothesis testing hierarchy.
- To ensure clinical stability of patients entering the trial, 2 inclusion criteria were modified: Criterion 3: patients were required to take a stable dose of antipsychotic
medication(s) for at least 12 weeks (instead of 8) prior to randomisation; Criterion 6: patients were required to have Clinical Global Impressions-Severity (CGI-S) score ≤4 at both Visits 1 and 2 (instead of only at Visit 1).
- Inclusion criteria 4 and 7 were slightly modified.
- A Japan-specific requirement for Informed consent form (ICF) signature was added. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
The study was terminated due to sponsor decision. The planned number of participants to be recruited was not reached. |