Overview

This trial has been terminated.

Condition down syndrome
Treatments placebo, ro5186582
Phase phase 2
Sponsor Hoffmann-La Roche
Start date October 2015
End date August 2016
Trial size 45 participants
Trial identifier NCT02484703, WP28760

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Primary purpose treatment
Masking participant, investigator
Arm
(Placebo Comparator)
Participants will receive matching placebo by mouth (PO) twice daily (BID) for up to 26 weeks.
placebo
Participants will receive matching placebo PO BID. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).
(Experimental)
Participants will receive RO5186582 at a dosage of 120 milligrams (mg) PO BID for up to 26 weeks.
ro5186582
Participants will receive 1 of 3 dosages of RO5186582 PO BID, including 40 mg, 60 mg, or 120 mg. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).
(Experimental)
Participants will receive RO5186582 at a dosage of 40 mg PO BID for up to 26 weeks.
ro5186582
Participants will receive 1 of 3 dosages of RO5186582 PO BID, including 40 mg, 60 mg, or 120 mg. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).
(Experimental)
Participants will receive RO5186582 at a dosage of 60 mg PO BID for up to 26 weeks.
ro5186582
Participants will receive 1 of 3 dosages of RO5186582 PO BID, including 40 mg, 60 mg, or 120 mg. Study medication will first be administered on Day 1, and only the morning dose will be given on the last day of treatment (Week 26).

Primary Outcomes

Measure
Percentage of Participants With Adverse Events (AEs)
time frame: Baseline up to Week 6
Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis
time frame: Baseline up to Week 6
Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the Columbia Classification Algorithm for Suicide Assessment (C-CASA)
time frame: Baseline up to Week 6
Anxiety, Depression, and Mood Scale (ADAMS) Score
time frame: Baseline up to Week 6
Hyperactivity and Impulsivity as Assessed by the Short Version of Conners Third Edition Parent Short-Form (Conners-3) Score
time frame: Baseline up to Week 6
Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score
time frame: Baseline up to Week 6
Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis
time frame: Baseline up to Week 6
Theta Power at Posterior Electrodes as Assessed Using EEG Analysis
time frame: Baseline up to Week 6
Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score
time frame: Baseline up to Week 6

Secondary Outcomes

Measure
Percentage of Participants With AEs
time frame: Baseline up to Week 26
Percentage of Participants With Epileptiform Abnormalities as Assessed Using EEG Analysis
time frame: Baseline up to Week 26
Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the C-CASA
time frame: Baseline up to Week 26
ADAMS Score
time frame: Baseline up to Week 26
Hyperactivity and Impulsivity as Assessed by the Short Version of Conners-3 Score
time frame: Baseline up to Week 26
Sleep Disturbances as Assessed by the CSHQ Score
time frame: Baseline up to Week 26
Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis
time frame: Baseline up to Week 26
Theta Power at Posterior Electrodes as Assessed Using EEG Analysis
time frame: Baseline up to Week 26
Cognition as Assessed by the CMS Subtests Score
time frame: Baseline up to Week 26
Adaptive Behavior as Assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) Score
time frame: Baseline up to Week 26
Clinical Global Impression-Improvement (CGI-I) Scale Score
time frame: Baseline up to Week 26
Daily Functional Memory as Assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) Score
time frame: Baseline up to Week 26
Intellectual Quotient (IQ) as Assessed by the Leiter 3
time frame: Baseline up to Week 26
Plasma Concentration of RO5186582
time frame: 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

Eligibility Criteria

All participants from 6 years up to 11 years old.

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)

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.