Dup15q Syndrome
Conditions
Keywords
dup15q, dup15q syndrome, 15q, duplication 15q, 15q duplication, chromosome 15q duplication, 15q duplication syndrome, duplication 15, triplication 15
Brief summary
This study consists of two parts. Part 1 will evaluate the safety, efficacy, and pharmacodynamics of 52-weeks of basmisanil treatment in children and adolescents (aged 2-14 years) with Dup15q syndrome. Part 1 will test the hypothesis that negative allosteric modulation of a GABAA receptor subtype can address excessive receptor function and positively impact core neurodevelopmental disease feature in individuals with Dup15q syndrome. Part 2 is an optional 2-year open-label extension to evaluate long-term safety, tolerability, and to provide supportive evidence of benefit of continued treatment with basmisanil in selected efficacy outcomes.
Interventions
DRUGBasmisanil
Participants will receive oral basmisanil at age-appropriate dosages
DRUGPlacebo
Participants will receive oral placebo
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* Documented maternal duplication (3 copies) or triplication (4 copies) of the chromosome 15q11.2-q13.1 region that includes the Prader Willi/Angelman critical region defined as \[BP2-BP3\] segment * Dup15q syndrome Clinician Global Impression of Severity scale (Dup15q CGI-S) overall severity score ≥ 4 (at least moderately ill) * Body weight equal to or above the third percentile for age * Participant has a parent, caregiver, or legally authorized representative (hereinafter "caregiver") of at least 18 years of age, who is fluent in the local language at the site, and capable and willing to provide written informed consent for the participant, according to International Council for Harmonisation and local regulations * Participant's caregiver must be living with the participant and, in the opinion of the Investigator, able and willing to reliably assess the participant's ongoing condition, to accompany the participant to all clinic visits, and ensure compliance to study treatment throughout the study. The same caregiver is able and willing to complete the caregiver assessments and is available to the Investigational Site by telephone or email if needed * Participant's caregiver is able and willing to use electronic devices to record information on the participant's condition and to complete assessments at home and agrees to home nursing visits, if local regulations allow for it and if home nursing service is available in the country/region
Exclusion criteria
* Uncontrolled epilepsy at screening (as defined by the protocol) * Lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years * Clinically significant ECG abnormalities at Screening * Clinically significant abnormalities in laboratory test results at screening (including positive results for HIV, hepatitis B and/or hepatitis C) * Allowed prior existing medication should be on a stable regimen (or frequency of intervention) for at least 6 weeks, and at least 8 weeks for anti-epileptic treatment, prior to Screening * Non-pharmacological / behavioral therapies should not be stopped or newly started at least 6 weeks prior to Screening and are expected to remain stable for the entire study duration (excluding changes related to standard age and educational interventional programs and minor interruptions such as illness or vacation * Concomitant use of prohibited medications * Participation in an investigational drug study within one month or within 6 × the elimination half-life, whichever is longer, prior to dosing in the study * Significant risk for suicidal behavior, as assessed through the suicidal behavior question adapted from the Columbia Classification Algorithm for Suicide Assessment (C-CASA) (participants ≥ 6 years of age only) * Known sensitivity to any of the study treatments or components thereof or drug or other allergy that, in the opinion of the Investigator, contraindicates the participation in the study, including severe lactose intolerance (e.g., unable to tolerate 250 mL \[8 oz. or 1 cup\] of milk, ice cream, or yogurt) * Concomitant clinically relevant disease or condition or any clinically significant finding at screening that could interfere with, or for which, the treatment might interfere with, the conduct of the study or that would pose an unacceptable risk to the participants in this study * Known active or uncontrolled bacterial, viral, or other infection (excluding fungal infections of nail beds) or any major clinically significant episode of infection or hospitalization (relating to the completion of the course of antibiotics) within 6 weeks prior to the start of drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores | Baseline, Day 183, Day 365 | The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. Standard scores for the adaptive behavior composite range from 20-160; lower scores indicate lower adaptive functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vineland-3 Gross and Fine Motor Subdomains Scores | Baseline, Day 183, Day 365 | The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the gross and fine motor domains range from 1-24; lower scores indicate lower adaptive functioning. |
| Vineland 3 Expressive and Receptive Communication Subdomains | Baseline, Day 183, Day 365 | The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the expressive and receptive communication subdomains range from 1-24; lower scores indicate lower adaptive functioning. |
| Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Baseline, Day 153, Day 365 | The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the play and leisure time, and interpersonal relationships subdomains range from 1-24; lower scores indicate lower adaptive functioning. |
| Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Baseline, Day 183, Day 365 | The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with total raw score ranges of 0-100 (gross motor) and 0-78 (fine motor). Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities. |
| MSEL Visual Reception Domain Scores | Baseline, Day 183 | The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with a total raw score range of 0-50. Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities. |
| MSEL Expressive and Receptive Language Subdomains | Baseline, Day 183 | The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with a total raw score range of 0-50 (expressive language) or 0-48 (receptive language). Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities. |
| Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Baseline until Day 395, or early termination (prior to Day 395) | The Dup15q CGI-S is a 10-domain clinician-rated measure on a 6-point scale that measures global severity of illness at a given point in time. The ten domains are seizures, expressive communication difficulties, fine motor skills difficulties, gross motor skills difficulties, cognitive/intellectual impairment, impairment in activities of daily living/self-care, socialization, maladaptive behavior, sleep difficulties, and overall severity. Response options are 1-none, 2-very mild, 3-mild, 4-moderate, 5-severe, and 6-very severe. |
| Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 28 - Day 395 or early termination (prior to Day 395) | The Dup15q CGI-C is a 10-domain clinician-rated measure on a 7-point scale that assesses the clinician's impression of change in illness compared with baseline. The ten domains are seizures, expressive communication difficulties, fine motor skills difficulties, gross motor skills difficulties, cognitive/intellectual impairment, impairment in activities of daily living/self-care, socialization, maladaptive behavior, sleep difficulties, and overall severity. Response options are 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse. The CGI does not yield a global score. |
| Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Baseline - Day 365, or early termination (prior to Day 365) | The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The irritability domain score range is 0-45, with higher score indicating greater severity. |
| ABC-2-C Domain Scores - Social Withdrawal | Baseline - Day 365, or early termination (prior to Day 365) | The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The social withdrawal domain score range is 0-48, with higher scores indicating greater severity. |
| ABC-2-C Domain Scores - Stereotypic Behavior | Baseline - Day 365, or early termination (prior to Day 365) | The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The stereotypic behavior subdomain score range is 0-21, with higher scores indicating greater severity. |
| ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Baseline until Day 365, or early termination (prior to Day 365) | The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The hyperactivity/non-compliance subdomain score range is 0-45, with higher scores indicating greater severity. |
| ABC-2-C Domain Scores - Inappropriate Speech | Baseline until Day 365, or early termination (prior to Day 365) | The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The inappropriate speech subdomain score range is 0-12, with higher scores indicating greater severity. |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 52 weeks | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Plasma Concentration of Basmisanil | Day 1 - Day 183 | — |
| Plasma Concentration of the Basmisanil Metabolite M1 | Day 1 - Day 183 | — |
| Quantitative EEG (qEEG) Beta-band Power | Baseline, Day 14 | This is the average of the EEG parameter 10 x Log\_10 of the total beta power between 16 and 32 Hz in microVolt\^2. |
Countries
Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Part 1: Participants received oral placebo twice (BID) on the first day of treatment, then three times daily (TID) to Day 365. | 2 |
| Basmisanil Part 1: Participants received oral basmisanil BID on the first day of treatment, then TID to Day 365.
Part 2: Participants who completed Part 1 were to receive oral basmisanil for approximately 2 years. | 5 |
| Total | 7 |
Baseline characteristics
| Characteristic | Basmisanil | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 8.8 Years STANDARD_DEVIATION 2.2 | 8.6 Years STANDARD_DEVIATION 1.9 | 8.0 Years STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 0 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants | — |
| Race (NIH/OMB) Asian | — | 0 Participants | — |
| Race (NIH/OMB) Black or African American | — | 0 Participants | — |
| Race (NIH/OMB) More than one race | — | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — |
| Race (NIH/OMB) White | — | 0 Participants | — |
| Sex/Gender, Customized Female + Male | 5 Count of Participants | 7 Count of Participants | 2 Count of Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 5 |
| other Total, other adverse events | 2 / 2 | 5 / 5 |
| serious Total, serious adverse events | 0 / 2 | 1 / 5 |
Outcome results
Primary
Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores
The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. Standard scores for the adaptive behavior composite range from 20-160; lower scores indicate lower adaptive functioning.
Time frame: Baseline, Day 183, Day 365
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores | Baseline | 30.50 Units on a scale |
| Placebo | Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores | Day 183 | 28.00 Units on a scale |
| Placebo | Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores | Day 365 | 32.00 Units on a scale |
| Basmisanil | Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores | Baseline | 36.00 Units on a scale |
| Basmisanil | Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores | Day 183 | 32.00 Units on a scale |
Secondary
ABC-2-C Domain Scores - Hyperactivity/Non-Compliance
The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The hyperactivity/non-compliance subdomain score range is 0-45, with higher scores indicating greater severity.
Time frame: Baseline until Day 365, or early termination (prior to Day 365)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 183 | 39.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 92 | 40.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 274 | 40.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 365 | 33.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Baseline | 32.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 28 | 12.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Early Termination | 14.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Baseline | 19.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 28 | 22.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 92 | 18.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Hyperactivity/Non-Compliance | Day 183 | 18.00 Units on a scale |
Secondary
ABC-2-C Domain Scores - Inappropriate Speech
The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The inappropriate speech subdomain score range is 0-12, with higher scores indicating greater severity.
Time frame: Baseline until Day 365, or early termination (prior to Day 365)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | ABC-2-C Domain Scores - Inappropriate Speech | Day 183 | 1.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Inappropriate Speech | Day 92 | 3.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Inappropriate Speech | Day 274 | 3.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Inappropriate Speech | Day 365 | 2.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Inappropriate Speech | Baseline | 5.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Inappropriate Speech | Day 28 | 1.50 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Inappropriate Speech | Early Termination | 0.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Inappropriate Speech | Baseline | 2.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Inappropriate Speech | Day 28 | 0.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Inappropriate Speech | Day 92 | 0.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Inappropriate Speech | Day 183 | 0.00 Units on a scale |
Secondary
ABC-2-C Domain Scores - Social Withdrawal
The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The social withdrawal domain score range is 0-48, with higher scores indicating greater severity.
Time frame: Baseline - Day 365, or early termination (prior to Day 365)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | ABC-2-C Domain Scores - Social Withdrawal | Day 183 | 10.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Social Withdrawal | Day 92 | 10.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Social Withdrawal | Day 274 | 2.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Social Withdrawal | Day 365 | 4.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Social Withdrawal | Baseline | 14.50 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Social Withdrawal | Day 28 | 7.50 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Social Withdrawal | Early Termination | 22.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Social Withdrawal | Baseline | 16.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Social Withdrawal | Day 28 | 14.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Social Withdrawal | Day 92 | 12.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Social Withdrawal | Day 183 | 7.00 Units on a scale |
Secondary
ABC-2-C Domain Scores - Stereotypic Behavior
The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The stereotypic behavior subdomain score range is 0-21, with higher scores indicating greater severity.
Time frame: Baseline - Day 365, or early termination (prior to Day 365)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | ABC-2-C Domain Scores - Stereotypic Behavior | Day 183 | 4.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Stereotypic Behavior | Day 92 | 6.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Stereotypic Behavior | Day 274 | 8.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Stereotypic Behavior | Day 365 | 2.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Stereotypic Behavior | Baseline | 8.00 Units on a scale |
| Placebo | ABC-2-C Domain Scores - Stereotypic Behavior | Day 28 | 5.50 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Stereotypic Behavior | Early Termination | 11.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Stereotypic Behavior | Baseline | 6.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Stereotypic Behavior | Day 28 | 13.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Stereotypic Behavior | Day 92 | 14.00 Units on a scale |
| Basmisanil | ABC-2-C Domain Scores - Stereotypic Behavior | Day 183 | 6.00 Units on a scale |
Secondary
Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability
The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The irritability domain score range is 0-45, with higher score indicating greater severity.
Time frame: Baseline - Day 365, or early termination (prior to Day 365)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 92 | 17.00 Units on a scale |
| Placebo | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 183 | 20.00 Units on a scale |
| Placebo | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 274 | 16.00 Units on a scale |
| Placebo | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 365 | 13.00 Units on a scale |
| Placebo | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Baseline | 11.00 Units on a scale |
| Placebo | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 28 | 10.00 Units on a scale |
| Basmisanil | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 92 | 16.00 Units on a scale |
| Basmisanil | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Early Termination | 3.00 Units on a scale |
| Basmisanil | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 183 | 28.00 Units on a scale |
| Basmisanil | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Day 28 | 15.00 Units on a scale |
| Basmisanil | Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability | Baseline | 15.00 Units on a scale |
Secondary
Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores
The Dup15q CGI-C is a 10-domain clinician-rated measure on a 7-point scale that assesses the clinician's impression of change in illness compared with baseline. The ten domains are seizures, expressive communication difficulties, fine motor skills difficulties, gross motor skills difficulties, cognitive/intellectual impairment, impairment in activities of daily living/self-care, socialization, maladaptive behavior, sleep difficulties, and overall severity. Response options are 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse. The CGI does not yield a global score.
Time frame: Day 28 - Day 395 or early termination (prior to Day 395)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 92 | 3.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 274 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 365 | 3.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 183 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 28 | 3.50 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Early Termination | 4.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 28 | 3.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 92 | 3.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Day 183 | 3.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores | Follow-Up Day 395 | 3.00 Units on a scale |
Secondary
Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores
The Dup15q CGI-S is a 10-domain clinician-rated measure on a 6-point scale that measures global severity of illness at a given point in time. The ten domains are seizures, expressive communication difficulties, fine motor skills difficulties, gross motor skills difficulties, cognitive/intellectual impairment, impairment in activities of daily living/self-care, socialization, maladaptive behavior, sleep difficulties, and overall severity. Response options are 1-none, 2-very mild, 3-mild, 4-moderate, 5-severe, and 6-very severe.
Time frame: Baseline until Day 395, or early termination (prior to Day 395)
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 365 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 28 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 92 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 183 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 274 | 4.00 Units on a scale |
| Placebo | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Baseline | 4.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Follow-Up Day 395 | 5.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Baseline | 4.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 183 | 4.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 28 | 4.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Early Termination | 6.00 Units on a scale |
| Basmisanil | Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores | Day 92 | 4.00 Units on a scale |
Secondary
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Up to 52 weeks
Population: The safety analysis population is the same as the ITT population, assuming treatment is received as assigned at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Count of Participants |
| Placebo | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Count of Participants |
| Basmisanil | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 5 Count of Participants |
| Basmisanil | Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Count of Participants |
Secondary
MSEL Expressive and Receptive Language Subdomains
The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with a total raw score range of 0-50 (expressive language) or 0-48 (receptive language). Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities.
Time frame: Baseline, Day 183
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | MSEL Expressive and Receptive Language Subdomains | Expressive Language - Baseline | 12.50 Units on a scale |
| Placebo | MSEL Expressive and Receptive Language Subdomains | Receptive Language - Day 365 | 13.00 Units on a scale |
| Placebo | MSEL Expressive and Receptive Language Subdomains | Expressive Language - Day 365 | 7.00 Units on a scale |
| Placebo | MSEL Expressive and Receptive Language Subdomains | Receptive Language - Baseline | 10.00 Units on a scale |
| Placebo | MSEL Expressive and Receptive Language Subdomains | Receptive Language - Day 183 | 17.00 Units on a scale |
| Placebo | MSEL Expressive and Receptive Language Subdomains | Expressive Language - Day 183 | 23.00 Units on a scale |
| Basmisanil | MSEL Expressive and Receptive Language Subdomains | Expressive Language - Baseline | 17.00 Units on a scale |
| Basmisanil | MSEL Expressive and Receptive Language Subdomains | Receptive Language - Day 183 | 11.00 Units on a scale |
| Basmisanil | MSEL Expressive and Receptive Language Subdomains | Expressive Language - Day 183 | 6.00 Units on a scale |
| Basmisanil | MSEL Expressive and Receptive Language Subdomains | Receptive Language - Baseline | 16.00 Units on a scale |
Secondary
MSEL Visual Reception Domain Scores
The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with a total raw score range of 0-50. Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities.
Time frame: Baseline, Day 183
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | MSEL Visual Reception Domain Scores | Baseline | 14.00 Units on a scale |
| Placebo | MSEL Visual Reception Domain Scores | Day 183 | 21.00 Units on a scale |
| Placebo | MSEL Visual Reception Domain Scores | Day 365 | 13.00 Units on a scale |
| Basmisanil | MSEL Visual Reception Domain Scores | Baseline | 4.00 Units on a scale |
| Basmisanil | MSEL Visual Reception Domain Scores | Day 183 | 5.00 Units on a scale |
Secondary
Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains
The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with total raw score ranges of 0-100 (gross motor) and 0-78 (fine motor). Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities.
Time frame: Baseline, Day 183, Day 365
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Fine Motor - Day 365 | 11.00 Units on a scale |
| Placebo | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Gross Motor - Day 365 | 1.00 Units on a scale |
| Placebo | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Fine Motor - Baseline | 15.50 Units on a scale |
| Placebo | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Fine Motor - Day 183 | 18.00 Units on a scale |
| Placebo | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Gross Motor - Baseline | 20.50 Units on a scale |
| Placebo | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Gross Motor - Day 183 | 24.00 Units on a scale |
| Basmisanil | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Gross Motor - Baseline | 19.00 Units on a scale |
| Basmisanil | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Fine Motor - Day 183 | 9.00 Units on a scale |
| Basmisanil | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Gross Motor - Day 183 | 18.00 Units on a scale |
| Basmisanil | Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains | Fine Motor - Baseline | 15.00 Units on a scale |
Secondary
Plasma Concentration of Basmisanil
Time frame: Day 1 - Day 183
Population: The pharmacokinetic (PK) population consisted of all participants who received at least one dose of study treatment and who had data from at least one postdose sample. Only assessment time points with \> 1 participant are shown due to concerns that certain demographic characteristics that may be present in only one treatment arm, or the duration a participant was in the trial, present an unacceptable risk of participant re-identification.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of Basmisanil | Day 1 - Hour 1.5 | 2520 ng/mL | Standard Deviation 965 |
| Placebo | Plasma Concentration of Basmisanil | Day 1 - Hour 3.5 | 2220 ng/mL | Standard Deviation 955 |
| Placebo | Plasma Concentration of Basmisanil | Day 1 - Hour 5.5 | 1640 ng/mL | Standard Deviation 756 |
| Placebo | Plasma Concentration of Basmisanil | Day 1 - Hour 7.5 | 1040 ng/mL | Standard Deviation 392 |
| Placebo | Plasma Concentration of Basmisanil | Day 1 - Hour 9 | 791 ng/mL | Standard Deviation 368 |
| Placebo | Plasma Concentration of Basmisanil | Day 2 - Hour 0 | 731 ng/mL | Standard Deviation 535 |
| Placebo | Plasma Concentration of Basmisanil | Day 2 - Hour 1.5 | 2380 ng/mL | Standard Deviation 576 |
| Placebo | Plasma Concentration of Basmisanil | Day 2 - Hour 3.5 | 2210 ng/mL | Standard Deviation 864 |
| Placebo | Plasma Concentration of Basmisanil | Day 14 - Hour -1.5 | 1210 ng/mL | Standard Deviation 1230 |
| Placebo | Plasma Concentration of Basmisanil | Day 14 - Hour 0 | 902 ng/mL | Standard Deviation 973 |
| Placebo | Plasma Concentration of Basmisanil | Day 14 - Hour 1.5 | 2480 ng/mL | Standard Deviation 355 |
| Placebo | Plasma Concentration of Basmisanil | Day 14 - Hour 3.5 | 2160 ng/mL | Standard Deviation 698 |
| Placebo | Plasma Concentration of Basmisanil | Day 92 - Hour 0 | 896 ng/mL | Standard Deviation 689 |
Secondary
Plasma Concentration of the Basmisanil Metabolite M1
Time frame: Day 1 - Day 183
Population: The pharmacokinetic (PK) population consisted of all participants who received at least one dose of study treatment and who had data from at least one postdose sample. Only assessment time points with \> 1 participant are shown due to concerns that certain demographic characteristics that may be present in only one treatment arm, or the duration a participant was in the trial, present an unacceptable risk of participant re-identification.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 1 - Hour 1.5 | 1410 ng/mL | Standard Deviation 585 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 1 - Hour 3.5 | 1510 ng/mL | Standard Deviation 417 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 1 - Hour 5.5 | 985 ng/mL | Standard Deviation 335 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 1 - Hour 7.5 | 675 ng/mL | Standard Deviation 221 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 1 - Hour 9 | 535 ng/mL | Standard Deviation 173 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 2 - Hour 0 | 664 ng/mL | Standard Deviation 568 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 2 - Hour 1.5 | 1330 ng/mL | Standard Deviation 358 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 2 - Hour 3.5 | 1410 ng/mL | Standard Deviation 506 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 14 - Hour -1.5 | 1400 ng/mL | Standard Deviation 1410 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 14 - Hour 0 | 1060 ng/mL | Standard Deviation 1470 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 14 - 1.5 | 1510 ng/mL | Standard Deviation 413 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 14 - Hour 3.5 | 1250 ng/mL | Standard Deviation 540 |
| Placebo | Plasma Concentration of the Basmisanil Metabolite M1 | Day 92 - Hour 0 | 648 ng/mL | Standard Deviation 522 |
Secondary
Quantitative EEG (qEEG) Beta-band Power
This is the average of the EEG parameter 10 x Log\_10 of the total beta power between 16 and 32 Hz in microVolt\^2.
Time frame: Baseline, Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Quantitative EEG (qEEG) Beta-band Power | Day 14 | 9.44 µV2 | Standard Deviation 0.37 |
| Placebo | Quantitative EEG (qEEG) Beta-band Power | Baseline | 9.47 µV2 | Standard Deviation 0.21 |
| Basmisanil | Quantitative EEG (qEEG) Beta-band Power | Day 14 | 9.74 µV2 | Standard Deviation 1.05 |
| Basmisanil | Quantitative EEG (qEEG) Beta-band Power | Baseline | 11.39 µV2 | Standard Deviation 1.55 |
Secondary
Vineland 3 Expressive and Receptive Communication Subdomains
The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the expressive and receptive communication subdomains range from 1-24; lower scores indicate lower adaptive functioning.
Time frame: Baseline, Day 183, Day 365
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Vineland 3 Expressive and Receptive Communication Subdomains | Receptive Communication V-Scale Score - Day 365 | 1.00 Units on a scale |
| Placebo | Vineland 3 Expressive and Receptive Communication Subdomains | Expressive Communication V-Scale Score - Day 365 | 1.00 Units on a scale |
| Placebo | Vineland 3 Expressive and Receptive Communication Subdomains | Receptive Communication V-Scale Score - Baseline | 1.00 Units on a scale |
| Placebo | Vineland 3 Expressive and Receptive Communication Subdomains | Receptive Communication V-Scale Score - Day 183 | 1.00 Units on a scale |
| Placebo | Vineland 3 Expressive and Receptive Communication Subdomains | Expressive Communication V-Scale Score - Baseline | 1.00 Units on a scale |
| Placebo | Vineland 3 Expressive and Receptive Communication Subdomains | Expressive Communication V-Scale Score - Day 183 | 1.00 Units on a scale |
| Basmisanil | Vineland 3 Expressive and Receptive Communication Subdomains | Expressive Communication V-Scale Score - Baseline | 1.00 Units on a scale |
| Basmisanil | Vineland 3 Expressive and Receptive Communication Subdomains | Receptive Communication V-Scale Score - Day 183 | 1.00 Units on a scale |
| Basmisanil | Vineland 3 Expressive and Receptive Communication Subdomains | Expressive Communication V-Scale Score - Day 183 | 1.00 Units on a scale |
| Basmisanil | Vineland 3 Expressive and Receptive Communication Subdomains | Receptive Communication V-Scale Score - Baseline | 1.00 Units on a scale |
Secondary
Vineland-3 Gross and Fine Motor Subdomains Scores
The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the gross and fine motor domains range from 1-24; lower scores indicate lower adaptive functioning.
Time frame: Baseline, Day 183, Day 365
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Vineland-3 Gross and Fine Motor Subdomains Scores | Fine Motor V-Scale Score - Day 365 | 1.00 Units on a scale |
| Placebo | Vineland-3 Gross and Fine Motor Subdomains Scores | Fine Motor V-Scale Score - Day 183 | 1.00 Units on a scale |
| Placebo | Vineland-3 Gross and Fine Motor Subdomains Scores | Gross Motor V-Scale Score - Baseline | 1.00 Units on a scale |
| Placebo | Vineland-3 Gross and Fine Motor Subdomains Scores | Gross Motor V-Scale Score - Day 183 | 4.00 Units on a scale |
| Placebo | Vineland-3 Gross and Fine Motor Subdomains Scores | Gross Motor V-Scale Score - Day 365 | 1.00 Units on a scale |
| Placebo | Vineland-3 Gross and Fine Motor Subdomains Scores | Fine Motor V-Scale Score - Baseline | 1.00 Units on a scale |
| Basmisanil | Vineland-3 Gross and Fine Motor Subdomains Scores | Gross Motor V-Scale Score - Baseline | 4.50 Units on a scale |
| Basmisanil | Vineland-3 Gross and Fine Motor Subdomains Scores | Fine Motor V-Scale Score - Baseline | 3.00 Units on a scale |
Secondary
Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains
The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the play and leisure time, and interpersonal relationships subdomains range from 1-24; lower scores indicate lower adaptive functioning.
Time frame: Baseline, Day 153, Day 365
Population: ITT population: All randomized participants who received ≥1 dose. Participants were allocated to the treatment arm they were randomized to.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Interpersonal Relationships V-Scale Score - Day 365 | 3.00 Units on a scale |
| Placebo | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Play and Leisure V-Scale Score - Day 365 | 1.00 Units on a scale |
| Placebo | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Interpersonal Relationships V-Scale Score - Baseline | 1.50 Units on a scale |
| Placebo | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Interpersonal Relationships V-Scale Score - Day 183 | 3.00 Units on a scale |
| Placebo | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Play and Leisure V-Scale Score - Baseline | 1.00 Units on a scale |
| Placebo | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Play and Leisure V-Scale Score - Day 183 | 1.00 Units on a scale |
| Basmisanil | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Play and Leisure V-Scale Score - Baseline | 1.00 Units on a scale |
| Basmisanil | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Interpersonal Relationships V-Scale Score - Day 183 | 1.00 Units on a scale |
| Basmisanil | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Play and Leisure V-Scale Score - Day 183 | 1.00 Units on a scale |
| Basmisanil | Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains | Interpersonal Relationships V-Scale Score - Baseline | 1.00 Units on a scale |