A Molecular and Functional Brain Imaging Study in Individuals With Down Syndrome and Healthy Controls Following Single Dose RG1662

NCT01667367 | Completed Phase 1

• 2 other identifiers: BP256112012-001301-24
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, single-blind, placebo-controlled, parallel-group study with crossover component will evaluate the GABAAalpha5 receptor expression, occupancy and functional connectivity in the brains of individuals with Down syndrome and healthy controls following single dose RG1662. Participants will receive a single dose of placebo before the imaging session (PET and MRI), and a single dose of RG1662 before the second imaging session.

Conditions

Healthy Volunteer, Down Syndrome

Outcome Measures

Primary Outcomes (3)

• Brain GABAA receptor alpha5 subunit localization/density assessed by positron emission tomography (PET)

  approximately 1 day

• Brain GABAA receptor alpha5 subunit occupancy following single dose of RG1662

  approximately 1 day

• Correlation of RG1662 plasma concentrations and GABAAalpha5 receptor occupancy

  approximately 12 months

Secondary Outcomes (3)

• Safety: Incidence of adverse events

  approximately 12 months

• Resting state functional brain connectivity following a single dose of either RG1662 or placebo, assessed by functional magnetic resonance imaging (fMRI)

  approximately 1 day

• Functional brain connectivity of individuals with Down syndrome versus healthy controls receiving placebo

  approximately 12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: placebo

RG1662

EXPERIMENTAL

Drug: RG1662

Interventions

RG1662 DRUG

Single oral dose

RG1662

placebo DRUG

Single oral dose

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy controls and individuals with Down syndrome:
• Male and female adults, 18 to 40 years of age
• Body mass index (BMI) 18 - 40 kg/m2 inclusive
• Females of child-bearing potential and males with female partners of child-bearing potential must agree to use two medically approved methods of contraception, one of which must be a barrier method, for the duration of the study and for 4 months after the last study drug administration
• Clinical laboratory values within normal limits or abnormalities considered not significant by the investigator and sponsor; individuals with thyroid disease may be included in the study provided they are euthyroid and stable on treatment for at least one month prior to screening
• Individuals with Down syndrome must also meet the following:
• Diagnosis of Down syndrome confirmed by karyotype; subjects may have free trisomy 21 or Robertsonian translocations; mosaic Down syndrome will be excluded
• Individuals must have a parent or other reliable caregiver who agrees to accompany the inidvidual to all clinic visits, provide information about the individual as required by protocol, and be willing to give informed consent

You may not qualify if:

• Regular smoker (\>5 cigarettes or equivalent: 3 cigars, 6 cigarillos, 3 pipes per day)
• Concomitant disease or condition or any clinically significant finding at screening that could interfere with, or for which the treatment might interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Severe head trauma or CNS infections (e.g. meningitis)
• History of epilepsy or seizures other than benign febrile convulsions of childhood
• Any confirmed significant allergic reactions against any drug, anaphylaxis or severe environmental allergies as judged by the investigator
• Positive for hepatitis B, hepatitis C or HIV infection
• Positive urine test at screening or at follow-up for drugs of abuse, or positive alcohol breath test at screening and prior to dosing
• Pregnant or lactating women
• Individuals with evidence or meeting clinical diagnosis of dementia

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Unknown Facility

London, NW10 7EW, United Kingdom

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 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2012
• First Posted: August 17, 2012
• Study Start: August 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: September 2, 2015

Record last verified: 2015-09

Locations

GB (1)