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

NCT02484703 | Terminated Phase 2

• 1 other identifier: WP28760
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 9

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.

Conditions

Down Syndrome

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants With Adverse Events (AEs)

  Baseline up to Week 6

• Percentage of Participants With Epileptiform Abnormalities as Assessed Using Electroencephalogram (EEG) Analysis

  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

• Anxiety, Depression, and Mood Scale (ADAMS) Score

  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

• Sleep Disturbances as Assessed by the Children's Sleep Habits Questionnaire (CSHQ) Score

  Baseline up to Week 6

• Gamma Power at Posterior Electrodes as Assessed Using EEG Analysis

  Baseline up to Week 6

• Theta Power at Posterior Electrodes as Assessed Using EEG Analysis

  Baseline up to Week 6

• Cognition as Assessed by the Children's Memory Scale (CMS) Subtests Score

  Baseline up to Week 6

Secondary Outcomes (14)

• 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

• Percentage of Participants by Suicidality Classification as Assessed Using an Adapted Form of the C-CASA

  Baseline up to Week 26

• ADAMS Score

  Baseline up to Week 26

• Hyperactivity and Impulsivity as Assessed by the Short Version of Conners-3 Score

  Baseline up to Week 26

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo by mouth (PO) twice daily (BID) for up to 26 weeks.

Drug: Placebo

RO5186582 120 mg BID

EXPERIMENTAL

Participants will receive RO5186582 at a dosage of 120 milligrams (mg) PO BID for up to 26 weeks.

Drug: RO5186582

RO5186582 40 mg BID

EXPERIMENTAL

Participants will receive RO5186582 at a dosage of 40 mg PO BID for up to 26 weeks.

Drug: RO5186582

RO5186582 60 mg BID

EXPERIMENTAL

Participants will receive RO5186582 at a dosage of 60 mg PO BID for up to 26 weeks.

Drug: RO5186582

Interventions

Placebo DRUG

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).

Placebo

RO5186582 DRUG

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).

RO5186582 120 mg BID; RO5186582 40 mg BID; RO5186582 60 mg BID

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

Southwest Autism Research & Resource Center

Phoenix, Arizona, 85006, United States

Location

Emory University School of Medicine; Department of Human Genetics & Pediatrics

Decatur, Georgia, 30033, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Massachusette General Hospital; Medical Genetics

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital, Department of Neurology

Boston, Massachusetts, 02115, United States

Location

Duke Clin Rsch Institute

Durham, North Carolina, 27710, United States

Location

UPMC Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15203 1101, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 30, 2015
• Study Start: October 28, 2015
• Primary Completion: August 3, 2016
• Study Completion: August 3, 2016
• Last Updated: July 6, 2017

Record last verified: 2017-07

Locations

US (9)