Fragile X Syndrome
Conditions
Keywords
Fragile X Syndrome, Martin-Bell Syndrome, Genetic Diseases, X-Linked, Escalante's syndrome
Brief summary
This Phase IIb study is designed to assess whether 3 doses of AFQ056 are safe and effective in treating the behavioral symptoms of Fragile X Syndrome.
Interventions
DRUGAFQ056
DRUGPlacebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Fragile X Syndrome, who are at least moderately ill based on a Clinical Global Impression Severity score of at least 4 and have qualifying scores on the ABC-C and IQ test at Visit 1
Exclusion criteria
* Advanced, severe or unstable disease that may interfere with the study outcome evaluations * Cancer within the past 5 years, other than localized skin cancer * Current treatment with more than two psychoactive medications, excluding anti-epileptics * History of severe self-injurious behavior * Weigh less than 32 kg * Females who are sexually active Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline to week 12 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline to week 12 | 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 |
| Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients | 12 weeks | 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. |
| Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients | 12 weeks | 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 |
| Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 12 weeks | 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. |
| Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 12 weeks | 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 |
| 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 | Baseline to week 12 | 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 |
| 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 | Baseline to week 12 | 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 |
| 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 | 12 weeks | 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. |
| 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 | 12 weeks | 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. |
| Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Baseline to week 12 | 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 |
| Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Baseline to week 12 | 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 |
| 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 | Baseline to week 12 | 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 |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Indonesia, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AFQ056 25 mg Bid 1 capsule of 25 mg and 1 capsule of placebo per intake | 31 |
| AFQ056 50 mg Bid 2 capsules of 25 mg per intake | 27 |
| AFQ056 100 mg Bid 1 capsule of 100 mg and 1 capsule of placebo per intake | 39 |
| Placebo 2 capsules of placebo per intake | 42 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 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
| Characteristic | AFQ056 25 mg Bid | AFQ056 50 mg Bid | AFQ056 100 mg Bid | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 14.4 Years STANDARD_DEVIATION 1.7 | 14.6 Years STANDARD_DEVIATION 1.58 | 14.6 Years STANDARD_DEVIATION 1.77 | 14.4 Years STANDARD_DEVIATION 1.85 | 14.5 Years STANDARD_DEVIATION 1.72 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 26 Participants | 24 Participants | 35 Participants | 39 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 42 | 22 / 31 | 9 / 27 | 30 / 39 |
| serious Total, serious adverse events | 2 / 42 | 0 / 31 | 0 / 27 | 0 / 39 |
Outcome results
Primary
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
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | -9.4 Score | Standard Error 3.88 |
Secondary
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
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | -2.8 Score | Standard Error 4.07 |
| AFQ056 100 mg Bid | 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 | -5.7 Score | Standard Error 4.06 |
| Placebo | 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 | -3.5 Score | Standard Error 4.3 |
Secondary
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)
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| Placebo | 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) | -3.4 Score | Standard Error 7.4 |
| AFQ056 100 mg Bid | 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) | -9.4 Score | Standard Error 3.88 |
Secondary
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
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | -1.0 Score | Standard Error 0.8 |
| Placebo | 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 | 1.1 Score | Standard Error 1.78 |
| Placebo | 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 | 2.2 Score | Standard Error 3.21 |
| Placebo | 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 1.1 |
| Placebo | 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 | -3.5 Score | Standard Error 1.53 |
| Placebo | 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 | 0.3 Score | Standard Error 0.78 |
| AFQ056 100 mg Bid | 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 | 1.3 Score | Standard Error 0.92 |
| AFQ056 100 mg Bid | 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 | 1.2 Score | Standard Error 0.67 |
| AFQ056 100 mg Bid | 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 | 0.7 Score | Standard Error 1.09 |
| AFQ056 100 mg Bid | 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 | -0.1 Score | Standard Error 0.5 |
| AFQ056 100 mg Bid | 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 | 0.9 Score | Standard Error 0.48 |
| AFQ056 100 mg Bid | 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 | 4.2 Score | Standard Error 1.94 |
| Placebo | 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 | -1.0 Score | Standard Error 0.42 |
| Placebo | 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 | -1.2 Score | Standard Error 0.42 |
| Placebo | 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 | -1.9 Score | Standard Error 0.78 |
| Placebo | 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 | -1.3 Score | Standard Error 0.95 |
| Placebo | 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 | -2.5 Score | Standard Error 1.67 |
| Placebo | 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 | -1.7 Score | Standard Error 0.58 |
Secondary
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
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 0.4 |
| Placebo | 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 | -0.9 Score | Standard Error 0.42 |
| Placebo | 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 | -0.3 Score | Standard Error 0.91 |
| Placebo | 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 | -1.3 Score | Standard Error 1.65 |
| Placebo | 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 | 0.1 Score | Standard Error 0.6 |
| Placebo | 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 | -0.4 Score | Standard Error 1.05 |
| Placebo | 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 | -0.1 Score | Standard Error 0.46 |
| AFQ056 100 mg Bid | 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 | -0.3 Score | Standard Error 1.05 |
| AFQ056 100 mg Bid | 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 | -1.0 Score | Standard Error 0.6 |
| AFQ056 100 mg Bid | 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 | -1.8 Score | Standard Error 0.91 |
| AFQ056 100 mg Bid | 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 | -1.1 Score | Standard Error 0.42 |
| AFQ056 100 mg Bid | 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 | -0.6 Score | Standard Error 0.47 |
| AFQ056 100 mg Bid | 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 | -0.8 Score | Standard Error 1.66 |
| Placebo | 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 | -0.8 Score | Standard Error 0.5 |
| Placebo | 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 | -1.1 Score | Standard Error 0.45 |
| Placebo | 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 1.11 |
| Placebo | 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 | -0.8 Score | Standard Error 0.96 |
| Placebo | 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 | 0.0 Score | Standard Error 1.75 |
| Placebo | 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 | 0.1 Score | Standard Error 0.64 |
Secondary
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Sameness behavior | -2.8 Score on a scale | Standard Error 1.42 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Compulsive behavior | -1.2 Score on a scale | Standard Error 1.06 |
| Placebo | 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 | 0.8 Score on a scale | Standard Error 0.53 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Ritualistic behavior | -2.2 Score on a scale | Standard Error 1.12 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Restricted behavior | -1.2 Score on a scale | Standard Error 0.74 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Stereotyped behavior | -1.5 Score on a scale | Standard Error 1.03 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Total score | -8.5 Score on a scale | Standard Error 3.95 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Compulsive behavior | 0.2 Score on a scale | Standard Error 0.6 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Total score | 1.5 Score on a scale | Standard Error 2.31 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Stereotyped behavior | 0.5 Score on a scale | Standard Error 0.64 |
| AFQ056 100 mg Bid | 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 | -0.2 Score on a scale | Standard Error 0.33 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Ritualistic behavior | 0.8 Score on a scale | Standard Error 0.66 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Sameness behavior | 0.3 Score on a scale | Standard Error 0.85 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Restricted behavior | -0.2 Score on a scale | Standard Error 0.46 |
| Placebo | 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 | -1.1 Score on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Restricted behavior | -1.1 Score on a scale | Standard Error 0.39 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Sameness behavior | -1.8 Score on a scale | Standard Error 0.73 |
| Placebo | 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 0.56 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Total score | -6.2 Score on a scale | Standard Error 2.03 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Ritualistic behavior | -0.6 Score on a scale | Standard Error 0.57 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum I | Compulsive behavior | -0.8 Score on a scale | Standard Error 0.51 |
Secondary
Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II
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
Time frame: Baseline to week 12
Population: 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
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 0.4 |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Sameness behavior | -1.6 Score on a scale | Standard Error 0.83 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Compulsive behavior | -1.5 Score on a scale | Standard Error 0.62 |
| Placebo | 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 | -0.7 Score on a scale | Standard Error 0.55 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Ritualistic behavior | -1.5 Score on a scale | Standard Error 0.58 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Restricted behavior | -0.7 Score on a scale | Standard Error 0.43 |
| Placebo | 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 0.56 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Total score | -5.9 Score on a scale | Standard Error 2.51 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Compulsive behavior | -0.2 Score on a scale | Standard Error 0.61 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Total score | -2.4 Score on a scale | Standard Error 2.47 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Stereotyped behavior | 0.4 Score on a scale | Standard Error 0.56 |
| AFQ056 100 mg Bid | 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 | 0.0 Score on a scale | Standard Error 0.56 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Ritualistic behavior | -1.0 Score on a scale | Standard Error 0.58 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Sameness behavior | -1.3 Score on a scale | Standard Error 0.82 |
| AFQ056 100 mg Bid | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Restricted behavior | -0.4 Score on a scale | Standard Error 0.42 |
| Placebo | 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 | 0.5 Score on a scale | Standard Error 0.59 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Restricted behavior | -0.3 Score on a scale | Standard Error 0.45 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Sameness behavior | -2.8 Score on a scale | Standard Error 0.88 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Stereotyped behavior | 0.2 Score on a scale | Standard Error 0.59 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Total score | -5.0 Score on a scale | Standard Error 2.67 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Ritualistic behavior | -1.8 Score on a scale | Standard Error 0.62 |
| Placebo | Change From Baseline in Repetitive Behaviors Assessed Using the Repetitive Behavior Scale - Revised (RBS-R) Total and Subscale Scores in Stratum II | Compulsive behavior | -1.0 Score on a scale | Standard Error 0.65 |
Secondary
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I
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.
Time frame: 12 weeks
Population: 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
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| AFQ056 100 mg Bid | 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 | 0.3 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 6 (Much worse) | 0 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 5 (Minimally worse) | 0 Participants | — |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 3 (Minimally improved) | 2 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 4 (No change) | 5 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 6 (Much worse) | 0 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 4 (No change) | 5 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 3 (Minimally improved) | 1 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 5 (Minimally worse) | 0 Participants | — |
| Placebo | 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 | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 2 (Much improved) | 0 Participants | 0.2 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 1 (Very much improved) | 0 Participants | 0.34 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 4 (No change) | 6 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 1 (Very much improved) | 0 Participants | 0.22 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 2 (Much improved) | 3 Participants | 0.2 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 3 (Minimally improved) | 3 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 5 (Minimally worse) | 3 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 6 (Much worse) | 0 Participants | — |
| AFQ056 100 mg Bid | 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 | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 3 (Minimally improved) | 11 Participants | — |
| Placebo | 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 | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 6 (Much worse) | 0 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 2 (Much improved) | 4 Participants | 0.21 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 1 (Very much improved) | 0 Participants | 0.18 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 5 (Minimally worse) | 1 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum I | 4 (No change) | 6 Participants | — |
Secondary
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II
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
Time frame: 12 weeks
Population: 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
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 4 (No change) | 12 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 3 (Minimally improved) | 7 Participants | — |
| AFQ056 100 mg Bid | 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 | 0.3 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 6 (Much worse) | 0 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 5 (Minimally worse) | 1 Participants | — |
| AFQ056 100 mg Bid | 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 |
| AFQ056 100 mg Bid | 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 | — |
| Placebo | 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 | 0.34 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 2 (Much improved) | 5 Participants | 0.2 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 3 (Minimally improved) | 9 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 4 (No change) | 5 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 5 (Minimally worse) | 2 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 6 (Much worse) | 0 Participants | — |
| Placebo | 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 | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 2 (Much improved) | 3 Participants | 0.2 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 4 (No change) | 11 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 5 (Minimally worse) | 2 Participants | — |
| AFQ056 100 mg Bid | 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 | 0.22 |
| AFQ056 100 mg Bid | 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 | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 6 (Much worse) | 0 Participants | — |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 3 (Minimally improved) | 4 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 3 (Minimally improved) | 5 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 6 (Much worse) | 1 Participants | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 4 (No change) | 8 Participants | — |
| Placebo | 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 | 0.18 |
| Placebo | 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 | — |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 2 (Much improved) | 4 Participants | 0.21 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression-Improvement (CGI-I) Scale in Stratum II | 5 (Minimally worse) | 0 Participants | — |
Secondary
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients
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
Time frame: 12 weeks
Population: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 100 mg Bid | 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 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients | 3.2 Score | Standard Error 0.2 |
| AFQ056 100 mg Bid | 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 0.2 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum II Patients | 3.4 Score | Standard Error 0.21 |
Secondary
Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients
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.
Time frame: 12 weeks
Population: 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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 100 mg Bid | 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 0.3 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients | 3.8 Score | Standard Error 0.34 |
| AFQ056 100 mg Bid | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients | 3.5 Score | Standard Error 0.22 |
| Placebo | Global Improvement of Symptoms in Fragile X Using the Clinical Global Impression- Improvement (CGI-I) Scale in Stratum I Patients | 3.1 Score | Standard Error 0.18 |
Secondary
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
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.
Time frame: 12 weeks
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | 0 Number of participants |
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | 2 Number of participants |
Secondary
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
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.
Time frame: 12 weeks
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | 4 Number of participants |
| AFQ056 100 mg Bid | 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 |
| Placebo | 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 | 2 Number of participants |