Clinical Trial Results:
A Multi-center, Randomized, Double Blind, Placebo Controlled Phase 2 Study of the Efficacy, Safety and Tolerability of RO5186582 in Adults and Adolescents with Down Syndrome (CLEMATIS).
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Summary
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EudraCT number |
2013-001263-23 |
Trial protocol |
GB ES IT |
Global end of trial date |
04 May 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Nov 2016
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First version publication date |
20 Nov 2016
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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 |
BP27832
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02024789 | ||
WHO universal trial number (UTN) |
U1111-1150-1189 | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001506-PIP02-14 | ||
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 |
04 May 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
04 May 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to evaluate the efficacy of 26 weeks of treatment with basmisanil (RG1662, RO5186582) on a composite endpoint derived from clinically meaningful responses in working memory and on the level of independent functioning/adaptive behavior or global improvement as compared to placebo.
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Protection of trial subjects |
All study subjects/subjects' legally authorized representatives and caregivers were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Apr 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Spain: 47
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
France: 24
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Argentina: 1
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Mexico: 8
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Country: Number of subjects enrolled |
New Zealand: 3
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Country: Number of subjects enrolled |
United States: 77
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Worldwide total number of subjects |
170
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EEA total number of subjects |
80
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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) |
85
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Adults (18-64 years) |
85
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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 |
- | ||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 239 subjects were screened for entry into the study of whom 66 failed screening. A total of 173 subjects were randomized. Three subjects were randomized in error and were withdrawn before receiving any study treatment. A total of 170 subjects were in the study and received at least one dose of study medication. | ||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
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 |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with matching placebo for 26 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 |
Tablet, Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet or granule formulation was chosen by each subject at time of randomisation. Matching placebo was administered orally twice daily for 26 weeks.
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Arm title
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Basmisanil 120 mg (80 mg) bid | ||||||||||||||||||||||||||||||||
Arm description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 120 milligrams (80 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Basmisanil
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Investigational medicinal product code |
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Other name |
RG1662, RO5186582
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Pharmaceutical forms |
Tablet, Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet or granule formulation was chosen by each subject at time of randomisation. 120 mg (80 mg dosage for subjects 12-13 years old) basmisanil was administered orally twice daily for 26 weeks.
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Arm title
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Basmisanil 240 mg (160 mg) bid | ||||||||||||||||||||||||||||||||
Arm description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 240 milligrams (160 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Basmisanil
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Investigational medicinal product code |
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Other name |
RG1662, RO5186582
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Pharmaceutical forms |
Tablet, Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet or granule formulation was chosen by each subject at time of randomisation. 240 mg (160 mg dosage for subjects 12-13 years old) basmisanil was administered orally twice daily for 26 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with matching placebo for 26 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Basmisanil 120 mg (80 mg) bid
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 120 milligrams (80 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Basmisanil 240 mg (160 mg) bid
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 240 milligrams (160 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with matching placebo for 26 weeks. | ||
Reporting group title |
Basmisanil 120 mg (80 mg) bid
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 120 milligrams (80 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. | ||
Reporting group title |
Basmisanil 240 mg (160 mg) bid
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 240 milligrams (160 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. | ||
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End point title |
Percentage of Responders | ||||||||||||||||
End point description |
The endpoint was derived from responses in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Vineland Adaptive Behavior Scale (VABS) or global improvement Clinical Global Impression (CGI). A subject was a responder if (s)he had a relevant improvement from baseline in at least 2 out of 3 RBANS tasks (change of at least 2 points in List Learning, change of at least 1 point in List Learning and/or List Recall) as well as an increase from baseline in VABS composite score of >/=7 or a final assessment of CGI-Improvement (CGI-I) </= 3. Changes in VABS composite score and final CGI-I had to be consistent per individual. The modified intent-to-treat (mITT) population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The per protocol (PP) population reported here was the mITT population excluding subjects with major protocol violations.
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End point type |
Primary
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End point timeframe |
Week 26
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Statistical analysis title |
Basmisanil arms versus placebo | ||||||||||||||||
Statistical analysis description |
The difference in the percentage of responders between treatment groups was analyzed by means of a logistic regression model.
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Comparison groups |
Placebo v Basmisanil 120 mg (80 mg) bid v Basmisanil 240 mg (160 mg) bid
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Number of subjects included in analysis |
141
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.262 | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Confidence interval |
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End point title |
Change From Baseline of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) List Learning, List Recognition and List Recall at Week 26 | ||||||||||||||||||||||||||||||||||||||||
End point description |
The following 3 subtests of the RBANS were used: List Learning (score range 0-40), List Recognition (score range 0-20) and List Recall (score range 0-10). Higher scores indicate better cognitive function. A positive change from baseline indicates an improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [1] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of Vineland Adaptive Behavior Scale (VABS) Composite Score at Week 26 | ||||||||||||||||||||||||
End point description |
The VABS-version II measures personal and social skills such as communication, daily living skills, and socialization and provides a composite score reflecting an individual’s overall function. The survey interview form was used and administered to parents or caregivers using a semi-structured interview format. Reported here is the global score (adaptive behaviors composite). Higher scores indicate a higher level of function. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [2] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Clinical Global Impression-Improvement (CGI-I) Score | ||||||||||||||||
End point description |
The CGI-I is a 7-point scale that requires the clinician to assess how much the subject's illness has improved or worsened relative to a baseline state at the beginning of the intervention, and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Score ranges from 1-7 with a lower score indicating an improved outcome relative to baseline. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Week 26
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline of RBANS Story Memory, Picture Naming, Semantic Fluency and Digit Span at Week 26 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The following 4 subtests of the RBANS were evaluated: story memory (score range 0-12), picture naming (score range 0-10), semantic fluency (score range 0-40) and digit span (score range 0-16). Higher scores indicate better cognitive function. A positive change from baseline indicates an improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [3] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of VABS Domain Standardised Scores (Communication, Socialisation, Daily Living Skills) at Week 26 | ||||||||||||||||||||||||||||||||||||||||
End point description |
Reported here are the VABS domain standardised scores (communication, socialisation, daily living skills). Higher scores indicate a higher level of function. A positive change from baseline indicates an improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [4] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of Rivermead Behavioral Memory Test Children’s Version (RBMT-C) Subtest Endpoints at Week 26 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The RBMT-C comprises a number of subtests, each attempting to provide an objective measure of a range of everyday memory problems reported and observed in subjects with memory difficulties. Subtests analysed include 1 Delayed route recall (score range: 0-5), 2 Delayed story total (0.0-62.0), 3 Immediate story total (0.0-62.0), 4 Orientation questions (0.0-11.0), 5 Remembering a name (0-4), 6 Remembering a short route (0-5), 7 Remembering the appointment (0-2), 8 Remembering the belonging (0-4), 9 Remembering to deliver a message 1 (0-3), 10 Remembering to deliver a message 2 (0-3), 11 Test face recognition (0-5), and 12 Test for picture recognition (0-10). A positive change from baseline indicates improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [5] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of Clinical Evaluation of Language Fundamentals (CELF)-4 Subtest Endpoints at Week 26 | ||||||||||||||||||||||||||||||||||||||||
End point description |
CELF-4 subtests test language skills (ages 5 through 21). The Word Classes I subtest gives information about subject’s development of categorisation skills and ability to associate word meanings. If the subject was able to perform the Word Classes 1 (score range: 0-42) from the CELF-4 version without any zero scores on the receptive part of 7 consecutive items (i.e., reaching the ceiling of performance on the test), then the Word Classes 2 subtest (score range: 0-42) was used. The subtest Concepts and Following Directions (score range: 0-54; Con follow dir) was used to assess the capacity to follow spoken direction. Higher scores indicate better language skills. A positive change from baseline indicates improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [6] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of Observer Memory Questionnaire-Parent Form (OMQ-PF) Total Score at Week 26 | ||||||||||||||||||||||||
End point description |
The Observer Memory Questionnaire-Parent Form (OMQ-PF) is a 27-item questionnaire designed to ascertain parental perceptions about their child's memory function. All items are rated on a 5-point Likert scale (from 1=strongly agree to 5=strongly disagree, or 1=never to 5=always). Score range is 27-135 with higher scores indicating higher level of function. A positive change from baseline indicates improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was defined as the mITT excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [7] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change From Baseline of Behavior Rating Inventory of Executive Function Preschool (BRIEF-P) Endpoints at Week 26 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The BRIEF-P is a questionnaire of everyday skills reflective of abilities in the executive domain. Scores were derived for the following scales: Emergent Metacognition Index (EMI; score range 27-81), Emotional Control (EC; 10-30), Flexibility Index (FI; 20-60), Global Executive Composite (GEC; 63-189), Inhibitory Self-Control Index (ISCI; 26-78), Inconsistency (0-20), Inhibit (16-48), Negativity (0-10), Plan/Organize (P/O; 10-30), Shift (10-30) and Working Memory (WM; 17-51). Lower scores indicate higher level of function. A negative change from baseline indicates improvement. The mITT population included all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment. The PP population reported here was the mITT population excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [8] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of Pediatric Quality of Life Inventory (PedsQL) Cognitive Functioning Scale Scores and the PedsQL Generic Core Scale at Week 26 | ||||||||||||||||||||||||||||||||
End point description |
PedsQL integrates generic and disease-specific instruments. Two modules were used; 1) the Cognitive Functioning Scale (CFS), containing 6 items and 2) the Generic and Cognitive Module (GCM) consisting of 23 items encompassing 4 core domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); School Functioning (5 items). Both modules use a 5-point Likert-type response scale (0 = never a problem to 4 = almost always a problem). The items of the PedsQL modules are reverse-scored and linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that higher scores indicate better outcomes (e.g., less negative impact). A positive change from baseline indicates an improvement. The PP population reported here was the mITT population (all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment) excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [9] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline of PedsQL Family Impact Scale Score at Week 26 | ||||||||||||||||||||||||
End point description |
Caregivers completed the PedsQL Family Impact Module version 2 to measure the impact on a parent of caring for a subject with an acute or chronic condition. It encompasses 1) Physical Functioning (6 items), 2) Emotional Functioning (5 items), 3) Social Functioning (4 items), 4) Cognitive Functioning (5 items), 5) Communication (3 items), 6) Worry (5 items), 7) Daily Activities (3 items) and 8) Family Relationships (5 items). For each item a 5-point response scale is utilized (0 = never a problem to 4 = always a problem). The PedsQL module is reverse-scored and linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that higher scores indicate less negative impact. A positive change from baseline indicates improvement. The PP population reported was the mITT population (all subjects randomised, who received at least one dose of double-blind study medication and provided at least one post dose assessment) excluding subjects with major protocol violations.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [10] - Here, n in the subcategory title is the number of subjects analysed for each arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Safety: Percentage of Subjects with Adverse Events | ||||||||||||||||
End point description |
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. The safety analysis population includes all subjects who received at least one dose of the study medication, whether prematurely withdrawn from the study or not. For the safety population analysis, data are analysed according to treatment actually taken.
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End point type |
Secondary
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End point timeframe |
Up to Week 32
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Pharmacokinetics: Basmisanil Plasma Concentrations [11] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Pharmacokinetic (PK) population included those subjects who were evaluated for plasma concentration. Here, n in the subcategory title is the number of subjects analysed in each arm.
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End point type |
Secondary
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End point timeframe |
Day 1 at 0.5 hours (hr), 2 hr, 4 hr, 6 hr, Day 14 predose, Day 14, 2 hr, 4 hr, 6 hr, Day 42 predose, 2 hr, 4 hr, 6 hr, Day 84 predose, Day 140 and Day 182
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| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Basmisanil concentrations were not measured in the placebo arm as these subjects did not receive basmisanil treatment. |
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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 |
From baseline up to end of treatment (EOT) at Week 26 and up to follow-up visit 2 four to six weeks after EOT (Weeks 30-32).
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Adverse event reporting additional description |
The safety analysis population included all subjects who received at least one dose of the study medication, whether prematurely withdrawn from the study or not. For the safety population analysis, data were analyzed according to treatment actually taken.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with matching placebo for 26 weeks. Follow-up visit 1 was one week after end of treatment (EOT) and follow-up visit 2 was four to six weeks after EOT. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Basmisanil 120 mg (80 mg) bid
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 120 milligrams (80 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. Follow-up visit 1 was one week after end of treatment (EOT) and follow-up visit 2 was four to six weeks after EOT. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Basmisanil 240 mg (160 mg) bid
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Reporting group description |
Male and female subjects 12−30 years of age (inclusive) with Down syndrome were treated with 240 milligrams (160 mg dosage for subjects 12-13 years old) basmisanil for 26 weeks. Follow-up visit 1 was one week after end of treatment (EOT) and follow-up visit 2 was four to six weeks after EOT. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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18 Apr 2014 |
In the inclusion criterion "Ability to complete the Clinical Evaluation of Language Fundamentals (CELF)−preschool 2 Word Classes task" the score was decreased from 7 to 4 for the adolescents. The coagulation test was performed at screening only as there was no rationale to monitor coagulation parameters throughout the study. In the Body-mass Index (BMI) criterion the upper end of the range was changed from 30 to 32 kg/m^2 for adolescents. |
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27 Apr 2015 |
The post-trial access to basmisanil was updated in accordance with Roche Global Policy on Continued Access to investigational medicinal products (IMPs). Exclusion criteria were revised to incorporate subjects with International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis in the study. Updates were made to allow for repeat testing in the event of laboratory test abnormalities to confirm results and prevent unnecessary screen failures. For serum creatinine, it was clarified that only values above the normal range were considered exclusionary. A post-treatment measurement of coagulation parameters was added to ensure the subject’s safety upon completing the trial. Based on the pharmacokinetic (PK) interim analysis low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol measurements were added and the PK sampling scheme for adolescents aged 12-17 years was reduced to harmonize with that already in use for the 18-30 year cohort. |
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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. | |||
| None reported | |||
