Clinical Trial Results:
Interventional, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Flexible-Dose Study of Lu AF11167 for the Treatment of Persistent Prominent Negative Symptoms in Patients With Schizophrenia
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Summary
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EudraCT number |
2018-001581-42 |
Trial protocol |
EE LV HU BG PL CZ |
Global end of trial date |
03 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Sep 2021
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First version publication date |
03 Sep 2021
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Other versions |
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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 |
17972A
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03793712 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
H. Lundbeck A/S
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Sponsor organisation address |
Otilliavej 9, Valby, Denmark, 2500
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Public contact |
LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.com
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Scientific contact |
LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.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 |
03 Sep 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Aug 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Sep 2020
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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 primary objective of the trial was to evaluate the efficacy of 2 fixed-flexible doses (1-2 milligrams [mg]/day and 3-4 mg/day) of Lu AF11167 as monotherapy on negative symptoms in participants with schizophrenia with persistent prominent negative symptoms.
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Protection of trial subjects |
This study was conducted in compliance with Good Clinical Practice.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Dec 2018
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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 |
Bulgaria: 68
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Country: Number of subjects enrolled |
Czechia: 2
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Estonia: 16
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Latvia: 7
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
Ukraine: 60
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Worldwide total number of subjects |
162
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EEA total number of subjects |
102
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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) |
162
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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 |
The study design included a 1- to 4-week Screening and Washout Period (to assess the eligibility of participants), a 1-week Placebo Run-in Period (to confirm the stability of participant's clinical condition as well as persistence of their prominent negative symptoms), a 12-week Double-blind Treatment Period, and a 2-week Safety Follow-up Period. | ||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants were randomly assigned (1:1:1) to double-blind treatment with Lu AF11167 1-2 mg/day, Lu AF11167 3-4 mg/day, or placebo for 12 weeks. | ||||||||||||||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||
Arm description |
Participants received placebo matched to Lu AF11167 tablet orally once daily for a total of 12 weeks. | ||||||||||||||||||||||||||||||||||||
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 |
Modified-release tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo matched to Lu AF11167 will be administered per schedule specified in the arm description.
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Arm title
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Lu AF11167 1-2 mg/day | ||||||||||||||||||||||||||||||||||||
Arm description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. If this dose was not tolerated after the first week of treatment, the dose was reduced to 1 mg/day once daily and participants stayed on that dose for the remainder of the study. Total treatment duration was 12 weeks. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lu AF11167
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Modified-release tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Lu AF11167 will be administered per dose and schedule specified in the arm description.
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Arm title
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Lu AF11167 3-4 mg/day | ||||||||||||||||||||||||||||||||||||
Arm description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 4 mg/day. If this dose was not tolerated after the first week of treatment, the dose was reduced to 3 mg/day once daily and participants stayed on that dose for the remainder of the study. Total treatment duration was 12 weeks. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lu AF11167
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Modified-release tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Lu AF11167 will be administered per dose and schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to Lu AF11167 tablet orally once daily for a total of 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lu AF11167 1-2 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. If this dose was not tolerated after the first week of treatment, the dose was reduced to 1 mg/day once daily and participants stayed on that dose for the remainder of the study. Total treatment duration was 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lu AF11167 3-4 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 4 mg/day. If this dose was not tolerated after the first week of treatment, the dose was reduced to 3 mg/day once daily and participants stayed on that dose for the remainder of the study. Total treatment duration was 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo matched to Lu AF11167 tablet orally once daily for a total of 12 weeks. | ||
Reporting group title |
Lu AF11167 1-2 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 2 mg/day. If this dose was not tolerated after the first week of treatment, the dose was reduced to 1 mg/day once daily and participants stayed on that dose for the remainder of the study. Total treatment duration was 12 weeks. | ||
Reporting group title |
Lu AF11167 3-4 mg/day
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Reporting group description |
Participants received Lu AF11167 tablet orally once daily at a starting dose of 4 mg/day. If this dose was not tolerated after the first week of treatment, the dose was reduced to 3 mg/day once daily and participants stayed on that dose for the remainder of the study. Total treatment duration was 12 weeks. | ||
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End point title |
Change From Baseline in Brief Negative Symptom Scale (BNSS) Total Score at Week 12 | ||||||||||||||||
End point description |
The BNSS is a brief clinician rating scale, intended to measure negative symptoms. It consists of 13 items organized into 6 subscales: anhedonia, distress, asociality, avolition, blunted affect and alogia. The items score the impairment. Items 1 to 4 were rated from 0 (Normal) to 6 (Extremely severe) and items 5 to 13 were rated from 0 (No impairment) to 6 (Severe deficit). The BNSS total score was calculated by summing the 13 individual items. The BNSS total scores range from 0 to 78. Full analysis set (FAS) included all randomized participants who took at least 1 dose of the double-blind study drug and who had a valid baseline assessment and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||
Statistical analysis description |
Analysis was performed using a restricted maximum likelihood-based mixed model for repeated measurements (MMRM) approach. The model included pooled country, visit, and treatment as fixed factors, and the Baseline BNSS total score as a continuous covariate. The treatment-by-week interaction and the Baseline BNSS total score-by-week interaction were also included.
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Comparison groups |
Placebo v Lu AF11167 1-2 mg/day
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Number of subjects included in analysis |
75
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.4076 | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
Least Square (LS) Mean Difference | ||||||||||||||||
Point estimate |
1.13
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-1.56 | ||||||||||||||||
upper limit |
3.82 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.36
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||
Statistical analysis description |
Analysis was performed using a restricted maximum likelihood-based MMRM approach. The model included pooled country, visit, and treatment as fixed factors, and the Baseline BNSS total score as a continuous covariate. The treatment-by-week interaction and the Baseline BNSS total score-by-week interaction were also included.
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Comparison groups |
Placebo v Lu AF11167 3-4 mg/day
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Number of subjects included in analysis |
77
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.5197 | ||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||
Point estimate |
0.87
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-1.81 | ||||||||||||||||
upper limit |
3.55 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.36
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End point title |
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Negative Symptom Factor score: Negative Symptoms at Week 12 | ||||||||||||||||
End point description |
PANSS is a clinician rated scale designed to measure severity of psychopathology in adult participants with schizophrenia, schizoaffective disorders and other psychotic disorders. It includes 3 sub-scales and 30 items: 7 items for positive scale (for example: delusions, conceptual disorganization, and hallucinatory behaviour), 7 items for negative scale (for example: blunted affect, emotional withdrawal, and poor rapport) and 16 items for general psychopathology scale (for example: somatic concern, anxiety, and guilt feelings). Each item is rated from 1 (no symptoms) to 7 (extremely severe symptom). PANSS total score: sum of all items and ranges from 30 to 210. Subscale scores: sum of items within each subscale. FAS: all randomized participants who took at least 1 dose of double-blind study drug and who had a valid baseline and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed'=participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in PANSS Negative Subscale Score at Week 12 | ||||||||||||||||
End point description |
PANSS is a clinician rated scale designed to measure severity of psychopathology in adult participants with schizophrenia, schizoaffective disorders, and other psychotic disorders. It includes 3 sub-scales and 30 items: 7 items for positive scale (for example: delusions, conceptual disorganization, and hallucinatory behaviour), 7 items for negative scale (for example: blunted affect, emotional withdrawal, and poor rapport) and 16 items for general psychopathology scale (for example: somatic concern, anxiety, and guilt feelings). Each item is rated from 1 (no symptoms) to 7 (extremely severe symptom). Subscale scores: sum of items within each subscale. FAS: all randomized participants who took at least 1 dose of double-blind study drug and who had a valid baseline and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed'=participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Clinical Global Impression — Schizophrenia Severity of Illness (CGI-SCH-S) Negative Symptoms Score at Week 12 | ||||||||||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. The CGI-SCH severity of illness category symptoms and overall severity were rated on a 7-point scale ranging from 1 (normal - not ill) to 7 (among the most severely ill). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. FAS: all randomized participants who took at least 1 dose of the double-blind study drug and who had a valid baseline and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Clinical Global Impression — Schizophrenia Degree of Change (CGI-SCH-DC) Negative Symptoms Score at Week 12 | ||||||||||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. In the CGI-SCH degree of change category symptoms and overall severity were rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. FAS included all randomized participants who took at least 1 dose of the double-blind study drug and who had a valid baseline assessment and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of Participants With a CGI-SCH-DC Negative Symptoms Response at Week 12 | ||||||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. In the CGI-SCH-DC degree of change category symptoms and overall severity were rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. CGI-SCH-DC negative symptoms response defined as a CGI-SCH-DC negative symptoms score of 1 or 2. All-patients-treated set (APTS) included all randomized participants who took at least 1 dose of the double-blind study drug. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With BNSS Response at Week 12 | ||||||||||||||||||||||||
End point description |
The BNSS is a brief clinician rating scale, intended to measure negative symptoms. It consists of 13 items organized into 6 subscales: anhedonia, distress, asociality, avolition, blunted affect and alogia. The items score the impairment. Items 1 to 4 were rated from 0 (Normal) to 6 (Extremely severe) and items 5 to 13 were rated from 0 (No impairment) to 6 (Severe deficit). The BNSS total score was calculated by summing the 13 individual items. The BNSS total scores range from 0 to 78. BNSS response defined as a 20%, 30%, or 40% decrease in BNSS total score. APTS included all randomized participants who took at least 1 dose of the double-blind study drug. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score at Week 12 | ||||||||||||||||
End point description |
The PSP is a clinician-rated scale designed and validated to measure a participant’s current level of social functioning. The PSP consists of 4 items: socially useful activities (including work and study), personal and social relationships, self-care, and disturbing and aggressive behaviours. The 4 items were assessed on a 6-point scale, from absent to very severe. Based on these assessments and their combination, individual scores were converted into a global score ranging from 1 to 100. FAS included all randomized participants who took at least 1 dose of the double-blind study drug and who had a valid baseline assessment and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in PANSS Total Score at Week 12 | ||||||||||||||||
End point description |
PANSS is a clinician rated scale designed to measure severity of psychopathology in adult participants with schizophrenia, schizoaffective disorders and other psychotic disorders. It includes 3 sub-scales and 30 items: 7 items for positive scale (for example: delusions, conceptual disorganization, and hallucinatory behaviour), 7 items for negative scale (for example: blunted affect, emotional withdrawal, and poor rapport) and 16 items for general psychopathology scale (for example: somatic concern, anxiety, and guilt feelings). Each item is rated from 1 (no symptoms) to 7 (extremely severe symptom). PANSS total score: sum of all items and ranges from 30 to 210. Subscale scores: sum of items within each subscale. FAS: all randomized participants who took at least 1 dose of double-blind study drug and who had a valid baseline and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed'=participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in PANSS Positive Subscale Scores at Week 12 | ||||||||||||||||
End point description |
PANSS is a clinician rated scale designed to measure severity of psychopathology in adult participants with schizophrenia, schizoaffective disorders, and other psychotic disorders. It includes 3 sub-scales and 30 items: 7 items for positive scale (for example: delusions, conceptual disorganization, and hallucinatory behaviour), 7 items for negative scale (for example: blunted affect, emotional withdrawal, and poor rapport) and 16 items for general psychopathology scale (for example: somatic concern, anxiety, and guilt feelings). Each item is rated from 1 (no symptoms) to 7 (extremely severe symptom). Subscale scores: sum of items within each subscale. FAS: all randomized participants who took at least 1 dose of double-blind study drug and who had a valid baseline and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed'=participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in CGI-SCH-S Overall Severity Score at Week 12 | ||||||||||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. The CGI-SCH severity of illness category symptoms and overall severity were rated on a 7-point scale ranging from 1 (normal - not ill) to 7 (among the most severely ill). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently, and no total score was derived. APTS included all randomized participants who took at least 1 dose of the double-blind study drug. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
CGI-SCH-DC Overall Severity Score at Week 12 | ||||||||||||||||
End point description |
The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in participants with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of 4 different groups of symptoms (positive, negative, cognitive, and depressive) and the overall severity of the disorder. In the CGI-SCH degree of change category symptoms and overall severity were rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement were scored independently and no total score was derived. CGI-SCH-DC negative symptoms response defined as a CGI-SCH-DC negative symptoms score of 1 or 2. APTS included all randomized participants who took at least 1 dose of the double-blind study drug. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Total Score at Week 12 | ||||||||||||||||
End point description |
The CDSS is a 9-item clinician rated scale specifically developed for the assessment of depression in participants with schizophrenia. The items on the CDSS were all typical depressive symptoms and do not appear to overlap with the negative symptoms of schizophrenia. All items were rated on a 4-point scale from 0 (absent) to 3 (severe). Anchor point descriptions were provided to aid differentiation between each item score. The first 8 items were rated on the basis of the participant’s responses to questions during a semi-structured interview; the ninth item was based on the clinician's assessment of the participant over the course of the interview. The total score ranges from 0 to 27. FAS included all randomized participants who took at least 1 dose of the double-blind study drug and who had a valid baseline assessment and at least 1 valid post-baseline assessment of the primary efficacy variable. 'Overall number of participants analyzed' = participants analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 14
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Adverse event reporting additional description |
APTS included all randomized participants who took at least 1 dose of the double-blind study drug.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AF11167 1-2 mg
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Reporting group description |
AF11167 1-2 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AF11167 3-4 mg
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Reporting group description |
AF11167 3-4 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Nov 2018 |
This amendment was prepared to update the heart-rate corrected QT interval using Fridericia’s correction formula (QTcF) withdrawal criteria, to update the Cogstate Schizophrenia Cognitive Battery, and to provide clarifications and corrections to the protocol. |
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13 Dec 2019 |
This amendment has been prepared to update inclusion criteria and exclusion criteria. Other minor clarifications and corrections were also made.
- Inclusion criterion was changed for the participants being known and treated by the site or investigator from 12 months to 6 months to align eligibility requirements across other
inclusion and exclusion criteria addressing stability of the participant.
- Inclusion criterion was updated to allow a 2nd antipsychotic used for sleep problems, if approved by the Medical Monitor, as sleep problems are common in this participant population.
- Inclusion criterion was updated to clarify that hospitalization for social reasons is not exclusionary.
- Exclusion criterion was updated to allow thyroid stimulating hormone (TSH) values outside of the reference range if deemed not clinically significant by the investigator and approved by the Medical Monitor. |
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11 May 2020 |
This amendment has been prepared to increase the number of sites, add an interim analysis for futility, add that re-screening may be allowed in certain circumstances, and to add the United
States as a participating country. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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. | |||
| Due to lack of efficacy based on the interim analysis, this study was terminated early. | |||
