Trial Outcomes & Findings for Safety and Efficacy of AFQ056 in Adolescent Patients With Fragile X Syndrome (NCT NCT01357239)
NCT ID: NCT01357239
Last Updated: 2015-05-12
Results Overview
The Aberrant Behavior Checklist-Community edition (ABC-C) is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose Fragile X Mental Retardation 1 (FMR1) gene was fully methylated
COMPLETED
PHASE2
139 participants
Baseline to week 12
2015-05-12
Participant Flow
Participant milestones
| Measure |
AFQ056 25 mg Bid
1 capsule of 25 mg and 1 capsule of placebo per intake
|
AFQ056 50 mg Bid
2 capsules of 25 mg per intake
|
AFQ056 100 mg Bid
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Stratum: All Patients
STARTED
|
31
|
27
|
39
|
42
|
|
Stratum: All Patients
COMPLETED
|
31
|
27
|
37
|
40
|
|
Stratum: All Patients
NOT COMPLETED
|
0
|
0
|
2
|
2
|
|
Stratum I: Fully-Methylated
STARTED
|
8
|
6
|
17
|
22
|
|
Stratum I: Fully-Methylated
COMPLETED
|
8
|
6
|
16
|
22
|
|
Stratum I: Fully-Methylated
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Stratum II: Partially-Methylated
STARTED
|
23
|
21
|
22
|
20
|
|
Stratum II: Partially-Methylated
COMPLETED
|
23
|
21
|
21
|
18
|
|
Stratum II: Partially-Methylated
NOT COMPLETED
|
0
|
0
|
1
|
2
|
Reasons for withdrawal
| Measure |
AFQ056 25 mg Bid
1 capsule of 25 mg and 1 capsule of placebo per intake
|
AFQ056 50 mg Bid
2 capsules of 25 mg per intake
|
AFQ056 100 mg Bid
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Stratum: All Patients
Adverse Event
|
0
|
0
|
1
|
1
|
|
Stratum: All Patients
Subject withdrew consent
|
0
|
0
|
1
|
1
|
|
Stratum I: Fully-Methylated
Adverse Event
|
0
|
0
|
1
|
0
|
|
Stratum II: Partially-Methylated
Adverse Event
|
0
|
0
|
0
|
1
|
|
Stratum II: Partially-Methylated
Subject withdrew consent
|
0
|
0
|
1
|
1
|
Baseline Characteristics
Safety and Efficacy of AFQ056 in Adolescent Patients With Fragile X Syndrome
Baseline characteristics by cohort
| Measure |
AFQ056 25 mg Bid
n=31 Participants
1 capsule of 25 mg and 1 capsule of placebo per intake
|
AFQ056 50 mg Bid
n=27 Participants
2 capsules of 25 mg per intake
|
AFQ056 100 mg Bid
n=39 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=42 Participants
2 capsules of placebo per intake
|
Total
n=139 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
14.4 Years
STANDARD_DEVIATION 1.70 • n=93 Participants
|
14.6 Years
STANDARD_DEVIATION 1.58 • n=4 Participants
|
14.6 Years
STANDARD_DEVIATION 1.77 • n=27 Participants
|
14.4 Years
STANDARD_DEVIATION 1.85 • n=483 Participants
|
14.5 Years
STANDARD_DEVIATION 1.72 • n=36 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
15 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=93 Participants
|
24 Participants
n=4 Participants
|
35 Participants
n=27 Participants
|
39 Participants
n=483 Participants
|
124 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Aberrant Behavior Checklist-Community edition (ABC-C) is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose Fragile X Mental Retardation 1 (FMR1) gene was fully methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=16 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=22 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the Aberrant Behavior Checklist-Community Edition (ABC-CFX) Total Score in Stratum I Patients Exposed to AFQ056 100 mg Bid
|
8.6 Score
Standard Error 4.48
|
-9.4 Score
Standard Error 3.88
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum II included patients whose FMR1 gene was partially methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=23 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=21 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=20 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=18 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the ABC-CFX Total Score in Stratum II Patients Exposed to All 3 Doses of AFQ056
|
-6.8 Score
Standard Error 3.88
|
-2.8 Score
Standard Error 4.07
|
-5.7 Score
Standard Error 4.06
|
-3.5 Score
Standard Error 4.30
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose FMR1 gene was fully methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=8 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=6 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=22 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Behavioral Symptoms of Fragile X Syndrome Using the ABC-CFX Total Score in Stratum I Patients Exposed to the Two Lower Doses of AFQ056 (25 mg Bid and 50 mg Bid)
|
-11.8 Score
Standard Error 6.43
|
-3.4 Score
Standard Error 7.40
|
-9.4 Score
Standard Error 3.88
|
—
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated.
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=8 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=6 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=15 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=22 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients
|
3.3 Score
Standard Error 0.30
|
3.8 Score
Standard Error 0.34
|
3.5 Score
Standard Error 0.22
|
3.1 Score
Standard Error 0.18
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum II included patients whose FMR1 gene was partially methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=23 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=21 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=20 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=18 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients
|
3.5 Score
Standard Error 0.19
|
3.2 Score
Standard Error 0.20
|
3.5 Score
Standard Error 0.20
|
3.4 Score
Standard Error 0.21
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated.
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=8 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=6 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=15 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=22 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
1 (Very much improved)
|
1 Participants
0.30
|
0 Participants
0.34
|
0 Participants
0.22
|
0 Participants
0.18
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
2 (Much improved)
|
0 Participants
0.19
|
0 Participants
0.20
|
3 Participants
0.20
|
4 Participants
0.21
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
3 (Minimally improved)
|
2 Participants
|
1 Participants
|
3 Participants
|
11 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
4 (No change)
|
5 Participants
|
5 Participants
|
6 Participants
|
6 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
5 (Minimally worse)
|
0 Participants
|
0 Participants
|
3 Participants
|
1 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
6 (Much worse)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
7 (Very much worse)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum II included patients whose FMR1 gene was partially methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=23 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=21 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=20 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=18 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
4 (No change)
|
12 Participants
|
5 Participants
|
11 Participants
|
8 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
7 (Very much worse)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
1 (Very much improved)
|
0 Participants
0.30
|
0 Participants
0.34
|
0 Participants
0.22
|
0 Participants
0.18
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
2 (Much improved)
|
3 Participants
0.19
|
5 Participants
0.20
|
3 Participants
0.20
|
4 Participants
0.21
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
3 (Minimally improved)
|
7 Participants
|
9 Participants
|
4 Participants
|
5 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
5 (Minimally worse)
|
1 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
|
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
6 (Much worse)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales: irritability (range 0 to 54); lethargy/withdrawal (range 0 to 39); stereotypic behavior (range 0 to 18); hyperactivity (range 0 to 30); inappropriate speech (range 0 to 12); and social avoidance (range 0 to 12) plus the total score (range 0 to 165) were considered. A negative change represents improvement. Stratum I included patients whose FMR1 gene was fully methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=8 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=6 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=16 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=22 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I
Lethargy/withdrawal
|
-1.4 Score
Standard Error 1.29
|
-3.5 Score
Standard Error 1.53
|
1.3 Score
Standard Error 0.92
|
-1.9 Score
Standard Error 0.78
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I
Irritability
|
-3.5 Score
Standard Error 2.74
|
2.2 Score
Standard Error 3.21
|
4.2 Score
Standard Error 1.94
|
-2.5 Score
Standard Error 1.67
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I
Stereotypic behavior
|
-2.2 Score
Standard Error 0.96
|
-2.2 Score
Standard Error 1.10
|
1.2 Score
Standard Error 0.67
|
-1.7 Score
Standard Error 0.58
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I
Hyperactivity
|
-3.9 Score
Standard Error 1.57
|
1.1 Score
Standard Error 1.78
|
0.7 Score
Standard Error 1.09
|
-1.3 Score
Standard Error 0.95
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I
Inappropriate speech
|
-0.8 Score
Standard Error 0.69
|
0.3 Score
Standard Error 0.78
|
0.9 Score
Standard Error 0.48
|
-1.0 Score
Standard Error 0.42
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum I
Social avoidance
|
-0.2 Score
Standard Error 0.71
|
-1.0 Score
Standard Error 0.80
|
-0.1 Score
Standard Error 0.50
|
-1.2 Score
Standard Error 0.42
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales: irritability (range 0 to 54); lethargy/withdrawal (range 0 to 39); stereotypic behavior (range 0 to 18); hyperactivity (range 0 to 30); inappropriate speech (range 0 to 12); and social avoidance (range 0 to 12) plus the total score (range 0 to 165) were considered. A negative change represents improvement. Stratum II included patients whose FMR1 gene was partially methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=23 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=21 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=20 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=18 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II
Irritability
|
-1.5 Score
Standard Error 1.58
|
-1.3 Score
Standard Error 1.65
|
-0.8 Score
Standard Error 1.66
|
0.0 Score
Standard Error 1.75
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II
Lethargy/withdrawal
|
-0.8 Score
Standard Error 1.00
|
-0.4 Score
Standard Error 1.05
|
-0.3 Score
Standard Error 1.05
|
-0.8 Score
Standard Error 1.11
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II
Stereotypic behavior
|
-1.4 Score
Standard Error 0.57
|
0.1 Score
Standard Error 0.60
|
-1.0 Score
Standard Error 0.60
|
0.1 Score
Standard Error 0.64
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II
Hyperactivity
|
-1.5 Score
Standard Error 0.87
|
-0.3 Score
Standard Error 0.91
|
-1.8 Score
Standard Error 0.91
|
-0.8 Score
Standard Error 0.96
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II
Inappropriate speech
|
-0.9 Score
Standard Error 0.44
|
-0.1 Score
Standard Error 0.46
|
-0.6 Score
Standard Error 0.47
|
-0.8 Score
Standard Error 0.50
|
|
Change From Baseline in Irritability, Lethargy/Withdrawal, Stereotypic Behavior, Hyperactivity, Inappropriate Speech, and Social Avoidance Assessed by the Individual Subscales of the ABC-CFX Scale in Stratum II
Social avoidance
|
-0.7 Score
Standard Error 0.40
|
-0.9 Score
Standard Error 0.42
|
-1.1 Score
Standard Error 0.42
|
-1.1 Score
Standard Error 0.45
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Total is the number of patients with non-missing baseline ABC-CFX total score and at least one nonmissing post-baseline ABC-CFX total score and CGI-I assessment
The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to ABC-CFX algorithm, for which 55 items and six subscales plus the total score were considered, and for which the total score ranks from 0 to 165. The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated; Stratum II included patients whose FMR1 gene was partially methylated.
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=8 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=6 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=17 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=22 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Proportion of Patients With Clinical Response, Where Response is Defined as a Reduction of at Least 25% From Baseline in the ABC-CFX Total Score and a Score of 1 (Very Much Improved) or 2 (Much Improved) on the CGI-I Scale, Stratum I
|
1 Number of participants
|
0 Number of participants
|
1 Number of participants
|
2 Number of participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Total is the number of patients with non-missing baseline ABC-CFX total score and at least one nonmissing post-baseline ABC-CFX total score and CGI-I assessment
The ABC-C is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to ABC-CFX algorithm, for which 55 items and six subscales plus the total score were considered, and for which the total score ranks from 0 to 165. The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale used to assess treatment response in psychiatric patients, and the score ranges from 1 to 7 (with 1 being "very much improved", 4 being "no change" to 7 being "very much worse"). Stratum I included patients whose FMR1 gene was fully methylated; Stratum II included patients whose FMR1 gene was partially methylated.
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=23 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=21 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=22 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=19 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Proportion of Patients With Clinical Response, Where Response is Defined as a Reduction of at Least 25% From Baseline in the ABC-CFX Total Score and a Score of 1 (Very Much Improved) or 2 (Much Improved) on the CGI-I Scale, Stratum II
|
1 Number of participants
|
4 Number of participants
|
1 Number of participants
|
2 Number of participants
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Repetitive Behavior Scale - Revised (RBS-R) is a rating tool that captures the breadth of repetitive behavior. It is a 43-item questionnaire filled by the caregivers. Each behavior assessed is rated from 0 (behavior does not occur) to 3 (behavior occurs and it is a severe problem). The total score ranks from 0 to 129. The behaviors are grouped into six domains: ritualistic behavior (range 0 to 18); sameness behavior (range 0 to 33); stereotypic behavior (range 0 to 18); self-injurious behavior (range 0 to 24); compulsive behavior (range 0 to 24); and restricted interests (range 0 to 12). A negative change represents improvement. Stratum I included patients whose FMR1 gene was fully methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=8 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=6 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=16 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=22 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Stereotyped behavior
|
-1.0 Score on a scale
Standard Error 0.91
|
-1.5 Score on a scale
Standard Error 1.03
|
0.5 Score on a scale
Standard Error 0.64
|
-1.0 Score on a scale
Standard Error 0.56
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Self-injurious behavior
|
0.0 Score on a scale
Standard Error 0.46
|
0.8 Score on a scale
Standard Error 0.53
|
-0.2 Score on a scale
Standard Error 0.33
|
-1.1 Score on a scale
Standard Error 0.28
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Compulsive behavior
|
-0.1 Score on a scale
Standard Error 0.84
|
-1.2 Score on a scale
Standard Error 1.06
|
0.2 Score on a scale
Standard Error 0.60
|
-0.8 Score on a scale
Standard Error 0.51
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Ritualistic behavior
|
-0.2 Score on a scale
Standard Error 0.93
|
-2.2 Score on a scale
Standard Error 1.12
|
0.8 Score on a scale
Standard Error 0.66
|
-0.6 Score on a scale
Standard Error 0.57
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Sameness behavior
|
-0.8 Score on a scale
Standard Error 1.19
|
-2.8 Score on a scale
Standard Error 1.42
|
0.3 Score on a scale
Standard Error 0.85
|
-1.8 Score on a scale
Standard Error 0.73
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Restricted behavior
|
0.0 Score on a scale
Standard Error 0.65
|
-1.2 Score on a scale
Standard Error 0.74
|
-0.2 Score on a scale
Standard Error 0.46
|
-1.1 Score on a scale
Standard Error 0.39
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
Total score
|
-2.3 Score on a scale
Standard Error 3.25
|
-8.5 Score on a scale
Standard Error 3.95
|
1.5 Score on a scale
Standard Error 2.31
|
-6.2 Score on a scale
Standard Error 2.03
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Full Analysis Set (FAS):all randomized patients who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline assessment for the primary efficacy parameter. Only participants who had a value at the given time and the assessment was within the window for analysis were included
The Repetitive Behavior Scale - Revised (RBS-R) is a rating tool that captures the breadth of repetitive behavior. It is a 43-item questionnaire filled by the caregivers. Each behavior assessed is rated from 0 (behavior does not occur) to 3 (behavior occurs and it is a severe problem). The total score ranks from 0 to 129. The behaviors are grouped into six domains: ritualistic behavior (range 0 to 18); sameness behavior (range 0 to 33); stereotypic behavior (range 0 to 18); self-injurious behavior (range 0 to 24); compulsive behavior (range 0 to 24); and restricted interests (range 0 to 12). A negative change represents improvement. Stratum II included patients whose FMR1 gene was partially methylated
Outcome measures
| Measure |
AFQ056 100 mg Bid
n=23 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=21 Participants
2 capsules of placebo per intake
|
AFQ056 100 mg Bid
n=20 Participants
1 capsule of 100 mg and 1 capsule of placebo per intake
|
Placebo
n=18 Participants
2 capsules of placebo per intake
|
|---|---|---|---|---|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Total score
|
-4.3 Score on a scale
Standard Error 2.36
|
-5.9 Score on a scale
Standard Error 2.51
|
-2.4 Score on a scale
Standard Error 2.47
|
-5.0 Score on a scale
Standard Error 2.67
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Stereotyped behavior
|
0.1 Score on a scale
Standard Error 0.53
|
0.1 Score on a scale
Standard Error 0.56
|
0.4 Score on a scale
Standard Error 0.56
|
0.2 Score on a scale
Standard Error 0.59
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Self-injurious behavior
|
-0.6 Score on a scale
Standard Error 0.53
|
-0.7 Score on a scale
Standard Error 0.55
|
0.0 Score on a scale
Standard Error 0.56
|
0.5 Score on a scale
Standard Error 0.59
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Compulsive behavior
|
-0.9 Score on a scale
Standard Error 0.58
|
-1.5 Score on a scale
Standard Error 0.62
|
-0.2 Score on a scale
Standard Error 0.61
|
-1.0 Score on a scale
Standard Error 0.65
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Ritualistic behavior
|
-0.1 Score on a scale
Standard Error 0.55
|
-1.5 Score on a scale
Standard Error 0.58
|
-1.0 Score on a scale
Standard Error 0.58
|
-1.8 Score on a scale
Standard Error 0.62
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Sameness behavior
|
-2.2 Score on a scale
Standard Error 0.77
|
-1.6 Score on a scale
Standard Error 0.83
|
-1.3 Score on a scale
Standard Error 0.82
|
-2.8 Score on a scale
Standard Error 0.88
|
|
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
Restricted behavior
|
-0.6 Score on a scale
Standard Error 0.40
|
-0.7 Score on a scale
Standard Error 0.43
|
-0.4 Score on a scale
Standard Error 0.42
|
-0.3 Score on a scale
Standard Error 0.45
|
Adverse Events
Placebo
AFQ056 25 mg Bid
AFQ056 50 mg Bid
AFQ056 100 mg Bid
Serious adverse events
| Measure |
Placebo
n=42 participants at risk
2 capsules of placebo per intake
|
AFQ056 25 mg Bid
n=31 participants at risk
1 capsule of 25 mg and 1 capsule of placebo per intake
|
AFQ056 50 mg Bid
n=27 participants at risk
2 capsules of 25 mg per intake
|
AFQ056 100 mg Bid
n=39 participants at risk
1 capsule of 100 mg and 1 capsule of placebo per intake
|
|---|---|---|---|---|
|
Infections and infestations
Appendicitis
|
2.4%
1/42
|
0.00%
0/31
|
0.00%
0/27
|
0.00%
0/39
|
|
Nervous system disorders
Convulsion
|
2.4%
1/42
|
0.00%
0/31
|
0.00%
0/27
|
0.00%
0/39
|
Other adverse events
| Measure |
Placebo
n=42 participants at risk
2 capsules of placebo per intake
|
AFQ056 25 mg Bid
n=31 participants at risk
1 capsule of 25 mg and 1 capsule of placebo per intake
|
AFQ056 50 mg Bid
n=27 participants at risk
2 capsules of 25 mg per intake
|
AFQ056 100 mg Bid
n=39 participants at risk
1 capsule of 100 mg and 1 capsule of placebo per intake
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/42
|
6.5%
2/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/42
|
9.7%
3/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/42
|
6.5%
2/31
|
3.7%
1/27
|
15.4%
6/39
|
|
General disorders
Fatigue
|
0.00%
0/42
|
0.00%
0/31
|
3.7%
1/27
|
5.1%
2/39
|
|
General disorders
Pyrexia
|
2.4%
1/42
|
6.5%
2/31
|
3.7%
1/27
|
7.7%
3/39
|
|
Infections and infestations
Influenza
|
4.8%
2/42
|
6.5%
2/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
6/42
|
22.6%
7/31
|
22.2%
6/27
|
12.8%
5/39
|
|
Infections and infestations
Oral herpes
|
0.00%
0/42
|
6.5%
2/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Infections and infestations
Rhinitis
|
0.00%
0/42
|
6.5%
2/31
|
3.7%
1/27
|
2.6%
1/39
|
|
Infections and infestations
Upper respiratory tract infection
|
9.5%
4/42
|
6.5%
2/31
|
3.7%
1/27
|
12.8%
5/39
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.4%
1/42
|
0.00%
0/31
|
3.7%
1/27
|
10.3%
4/39
|
|
Nervous system disorders
Headache
|
9.5%
4/42
|
12.9%
4/31
|
0.00%
0/27
|
25.6%
10/39
|
|
Psychiatric disorders
Anxiety
|
2.4%
1/42
|
0.00%
0/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/42
|
0.00%
0/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/42
|
0.00%
0/31
|
0.00%
0/27
|
15.4%
6/39
|
|
Psychiatric disorders
Self injurious behaviour
|
0.00%
0/42
|
0.00%
0/31
|
0.00%
0/27
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.4%
1/42
|
9.7%
3/31
|
3.7%
1/27
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/42
|
9.7%
3/31
|
0.00%
0/27
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.4%
1/42
|
6.5%
2/31
|
7.4%
2/27
|
2.6%
1/39
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/42
|
6.5%
2/31
|
0.00%
0/27
|
0.00%
0/39
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER