Clinical trial NCT02484703: A Study of RO5186582 in Down Syndrome Among Children 6 to 11 Years of Age
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group 26-Week Dose-Investigating Study to Explore the Pharmacokinetics, Pharmacodynamic Effects, Efficacy, Safety and Tolerability of RO5186582 in Children With Down Syndrome Aged 6-11 Years
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Down Syndrome
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 45
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, efficacy, and pharmacokinetic and pharmacodynamic activity of 3 different dosages of RO5186582 compared with placebo. A total of approximately 46 participants will be enrolled, in order to have at least 32 evaluable, and will be randomly assigned to 1 of 4 treatments in a 1:1:1:1 ratio, with 9 children per treatment arm. The target ratio between 6-8 years and 9-11 years age groups is approximately 1:1 in each treatment arm, with a minimum of 3 children per age group in each treatment arm.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Down syndrome, except for mosaic Down syndrome
* Available parent or caregiver to attend clinic visits and provide information about the participant's behavior and symptoms

Exclusion Criteria:

* Any primary psychiatric comorbid disorder
* History of infantile spasms, West syndrome, Lennox-Gastaut syndrome, early infantile epileptic encephalopathy, treatment-refractory epilepsy with cognitive/developmental regression, severe head trauma, or central nervous system (CNS) infection
* Seizure event of any type within 12 months prior to Screening or relevant changes in anti-epileptic drugs 6 weeks prior to enrollment
* Significant sleep disruption
* Significant gastrointestinal, renal, hepatic, endocrine, or cardiovascular disease
* New-onset or ongoing hematologic/oncologic disorder
* Severe lactose intolerance
* Participation in another clinical study within 1 month or 6 half-lives prior to first dose, or any extent of participation in Study BP29589 (NCT02451657)

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 6
measure: Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis
timeFrame: Baseline up to Week 6
measure: Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the Columbia Classification Algorithm for Suicide Assessment (C-CASA)
timeFrame: Baseline up to Week 6
measure: Anxiety, Depression, and Mood Scale (ADAMS) Score
timeFrame: Baseline up to Week 6
measure: Hyperactivity and Impulsivity as Assessed by the Short Version of Conners Third Edition Parent Short-Form (Conners-3) Score
timeFrame: Baseline up to Week 6
measure: Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score
timeFrame: Baseline up to Week 6
measure: Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis
timeFrame: Baseline up to Week 6
measure: Theta Power at Posterior Electrodes as Assessed Using EEG Analysis
timeFrame: Baseline up to Week 6
measure: Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score
timeFrame: Baseline up to Week 6
Secondary outcomes:
measure: Percentage of Participants With AEs
timeFrame: Baseline up to Week 26
measure: Percentage of Participants With Epileptiform Abnormalities as Assessed Using EEG Analysis
timeFrame: Baseline up to Week 26
measure: Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the C-CASA
timeFrame: Baseline up to Week 26
measure: ADAMS Score
timeFrame: Baseline up to Week 26
measure: Hyperactivity and Impulsivity as Assessed by the Short Version of Conners-3 Score
timeFrame: Baseline up to Week 26
measure: Sleep Disturbances as Assessed by the CSHQ Score
timeFrame: Baseline up to Week 26
measure: Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis
timeFrame: Baseline up to Week 26
measure: Theta Power at Posterior Electrodes as Assessed Using EEG Analysis
timeFrame: Baseline up to Week 26
measure: Cognition as Assessed by the CMS Subtests Score
timeFrame: Baseline up to Week 26
measure: Adaptive Behavior as Assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) Score
timeFrame: Baseline up to Week 26
measure: Clinical Global Impression-Improvement (CGI-I) Scale Score
timeFrame: Baseline up to Week 26
measure: Daily Functional Memory as Assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) Score
timeFrame: Baseline up to Week 26
measure: Intellectual Quotient (IQ) as Assessed by the Leiter 3
timeFrame: Baseline up to Week 26
measure: Plasma Concentration of RO5186582
timeFrame: Predose (2 predose samples separated by at least 1 hour) at Weeks 2 and 6; and predose or postdose (as convenient) during Weeks 10, 17, and 26
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center
state: Arizona
city: Decatur
country: United States
facility: Emory University School of Medicine; Department of Human Genetics & Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusette General Hospital; Medical Genetics
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital, Department of Neurology
state: Massachusetts
city: Durham
country: United States
facility: Duke Clin Rsch Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Western Psychiatric Institute and Clinic
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: