A Study of RO5186582 in Down Syndrome Among Children 6 to 11 Years of Age

Down Syndrome Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02484703
• Other study ID #: WP28760
• Status: Terminated
• Phase: Phase 2
• First received: June 16, 2015
• Last updated: July 4, 2017
• Start date: October 28, 2015
• Est. completion date: August 3, 2016

Study information

• Verified date: July 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: August 3, 2016
• Est. primary completion date: August 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

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)

Related Conditions & MeSH terms

• Down Syndrome
• Syndrome

Intervention

Drug:
• 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).
• 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).

Locations

Country	Name	City	State
United States	Boston Children's Hospital, Department of Neurology	Boston	Massachusetts
United States	Massachusette General Hospital; Medical Genetics	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Emory University School of Medicine; Department of Human Genetics & Pediatrics	Decatur	Georgia
United States	Duke Clin Rsch Institute	Durham	North Carolina
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Southwest Autism Research & Resource Center	Phoenix	Arizona
United States	UPMC Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs)		Baseline up to Week 6
Primary	Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis		Baseline up to Week 6
Primary	Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the Columbia Classification Algorithm for Suicide Assessment (C-CASA)		Baseline up to Week 6
Primary	Anxiety, Depression, and Mood Scale (ADAMS) Score		Baseline up to Week 6
Primary	Hyperactivity and Impulsivity as Assessed by the Short Version of Conners Third Edition Parent Short-Form (Conners-3) Score		Baseline up to Week 6
Primary	Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score		Baseline up to Week 6
Primary	Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis		Baseline up to Week 6
Primary	Theta Power at Posterior Electrodes as Assessed Using EEG Analysis		Baseline up to Week 6
Primary	Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score		Baseline up to Week 6
Secondary	Percentage of Participants With AEs		Baseline up to Week 26
Secondary	Percentage of Participants With Epileptiform Abnormalities as Assessed Using EEG Analysis		Baseline up to Week 26
Secondary	Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the C-CASA		Baseline up to Week 26
Secondary	ADAMS Score		Baseline up to Week 26
Secondary	Hyperactivity and Impulsivity as Assessed by the Short Version of Conners-3 Score		Baseline up to Week 26
Secondary	Sleep Disturbances as Assessed by the CSHQ Score		Baseline up to Week 26
Secondary	Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis		Baseline up to Week 26
Secondary	Theta Power at Posterior Electrodes as Assessed Using EEG Analysis		Baseline up to Week 26
Secondary	Cognition as Assessed by the CMS Subtests Score		Baseline up to Week 26
Secondary	Adaptive Behavior as Assessed by the Vineland Adaptive Behavior Scales-II (VABS-II) Score		Baseline up to Week 26
Secondary	Clinical Global Impression-Improvement (CGI-I) Scale Score		Baseline up to Week 26
Secondary	Daily Functional Memory as Assessed by the Observer Memory Questionnaire-Parent Form (OMQ-PF) Score		Baseline up to Week 26
Secondary	Intellectual Quotient (IQ) as Assessed by the Leiter 3		Baseline up to Week 26
Secondary	Plasma Concentration of RO5186582		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