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

Phase 2

Terminated

• Conditions: Down Syndrome
• Interventions: Drug: Placebo; Drug: RO5186582

• Registration Number: NCT02484703
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-16
• Study First Submitted QC: 2015-06-24
• Study First Posted: 2015-06-30
• Study Start: 2015-10-28
• Primary Completion: 2016-08-03
• Study Completion: 2016-08-03
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-04
• Last Update Posted: 2017-07-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive matching placebo by mouth (PO) twice daily (BID) for up to 26 weeks.
RO5186582 40 mg BID	RO5186582	Participants will receive RO5186582 at a dosage of 40 mg PO BID for up to 26 weeks.
RO5186582 120 mg BID	RO5186582	Participants will receive RO5186582 at a dosage of 120 milligrams (mg) PO BID for up to 26 weeks.
RO5186582 60 mg BID	RO5186582	Participants will receive RO5186582 at a dosage of 60 mg PO BID for up to 26 weeks.

Primary Outcome Measures

Name	Time	Method
Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score	Baseline up to Week 6
Anxiety, Depression, and Mood Scale (ADAMS) Score	Baseline up to Week 6
Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis	Baseline up to Week 6
Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis	Baseline up to Week 6
Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score	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)	Baseline up to Week 6
Hyperactivity and Impulsivity as Assessed by the Short Version of Conners Third Edition Parent Short-Form (Conners-3) Score	Baseline up to Week 6
Percentage of Participants With Adverse Events (AEs)	Baseline up to Week 6
Theta Power at Posterior Electrodes as Assessed Using EEG Analysis	Baseline up to Week 6

Secondary Outcome Measures

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

Trial Locations

Locations (9)

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, 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

UPMC Western Psychiatric Institute and Clinic; 🇺🇸 Pittsburgh, Pennsylvania, United States

Southwest Autism Research & Resource Center; 🇺🇸 Phoenix, Arizona, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Massachusette General Hospital; Medical Genetics; 🇺🇸 Boston, Massachusetts, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Boston Children's Hospital, Department of Neurology; 🇺🇸 Boston, Massachusetts, United States