A Phase 1, Randomized, Double-blind, Placebo-controlled Crossover Study of RG7314 on the Potential Regulation of Higher Brain Functions in Healthy Male Participants: Proof of Mechanism

NCT02205073 | Completed Phase 1

• 2 other identifiers: BP294122014-000867-42
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single site, randomized, double-blind, three period cross-over, placebo-controlled, proof of mechanism study in healthy male subjects. The study will investigate whether the directionality of brain activity and connectivity in response to intranasal vasopressin treatment is similar to earlier studies and explores the effect of short-term treatment with RG7314 on functional MRI as a pharmacodynamic marker. While in the scanner, the participants will be asked to perform a face matching task and a Theory of Mind task, among other assessments. Participants' exposure to study drug will be assessed and all participants will receive follow-up examination 1 and 4 weeks after last dose.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (3)

• Replication of AVP-induced inhibition of anterior cingulate cortex (ACC) activity, as measured by BOLD fMRI during a face matching task, differences between treatments

  After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo

• Replication of AVP-induced inhibition of functional connectivity, as measured by BOLD fMRI during a face matching task, differences between treatments

  After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo

• Effect of RG7314 on the modulation of AVP pathway effects on ACC activity, as measured by BOLD fMRI during a face matching task, differences between treatments

  After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo

Secondary Outcomes (4)

• Incidence of adverse events (AEs)

  Up to 12 weeks

• Effect of RG7314 on brain activity modulated by AVP during an implicit and explicit emotional face processing task as evaluated by BOLD fMRI

  After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo

• Effect of RG7314 on brain activity modulated by AVP during a Theory of Mind task, as evaluated by BOLD fMRI

  After 6 days of dosing with RG7314/placebo and 40 - 130 minutes after application of intranasal vasopressin/placebo

• RG7314 plasma concentrations

  0h, 2:20h, 3h to 4:30h, 4:30h postdose on Days 6, 20, and 34

Study Arms (3)

Dosing Period 1

PLACEBO COMPARATOR

Drug: Placebo RD + Placebo SD

Dosing Period 2

ACTIVE COMPARATOR

Drug: Placebo RD + AVP SD

Dosing Period 3

EXPERIMENTAL

Drug: RG7314 RD + AVP SD

Interventions

Placebo RD + AVP SD DRUG

Placebo (matching to study drug) repeat doses + intranasal AVP single dose

Dosing Period 2

Placebo RD + Placebo SD DRUG

Placebo (matching to study drug) repeat doses + intranasal Placebo (matching to intranasal AVP) single dose

Dosing Period 1

RG7314 RD + AVP SD DRUG

RG7314 repeat doses + intranasal AVP single dose

Dosing Period 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Right-handed, healthy non-smoker male adults, 18 to 45 years of age
• A body mass index between 18 to 32 kg/m2 inclusive and total weight in the range of 50-100 kg
• Participants and their partners of childbearing potential must use 2 methods of contraception, one of which must be a barrier method for the duration of the study and for 90 days after the last dose
• In the investigator's opinion, the subject is deemed appropriate for participation in the study, capable of following the study schedule of assessments and complying with the study restrictions and discontinuation of prohibited medication will not pose undue risks to the participants

You may not qualify if:

• History of alcohol and/or substance abuse/dependence
• History of relapsing or current psychiatric or neurological disorders
• Participants who, in the Investigator's judgment, pose a suicidal risk, or any subject with a history of suicidal attempts or behavior
• Positive results for serology test for HIV, Hepatitis B, hepatitis C viruses
• Confirmed (e.g. 2 consecutive measurements) clinically significant abnormality on 12-lead electrocardiogram (ECG), including a QTcF of \>/= 450 milliseconds
• Confirmed clinically significant abnormality in vital signs, clinical chemistry and/or urinalysis
• Active stomach ulcer disease or active gastrointestinal bleeding
• Personal or family history (first or second degree relatives) of cerebral aneurysm
• Personal history of stroke or traumatic head injury
• Confirmed clinically significant abnormality in parameters of hematology or coagulation
• History of coagulopathies, bleeding disorders or blood dyscrasias
• History of hematological malignancy or myelosuppression (including iatrogenic).
• Contraindications for MRI scans or any brain/head abnormalities restricting MRI eligibility
• Fulfillment of any of the MRI contraindications on the standard radiography screening questionnaire
• Use of prohibited medications within 2 weeks prior to randomization, or 5 half-lives (whichever is longer)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Unknown Facility

Leiden, 2333, Netherlands

Location

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: July 31, 2014
• Study Start: July 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 4, 2016

Record last verified: 2016-07

Locations

NL (1)