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

NCT ID: NCT02205073

Last Updated: 2016-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-10-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Dosing Period 1

Group Type: PLACEBO_COMPARATOR

Placebo RD + Placebo SD

Intervention Type: DRUG

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

Dosing Period 2

Group Type: ACTIVE_COMPARATOR

Placebo RD + AVP SD

Intervention Type: DRUG

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

Dosing Period 3

Group Type: EXPERIMENTAL

RG7314 RD + AVP SD

Intervention Type: DRUG

RG7314 repeat doses + intranasal AVP single dose

Interventions

Placebo RD + AVP SD

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

Intervention Type: DRUG

Placebo RD + Placebo SD

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

Intervention Type: DRUG

RG7314 RD + AVP SD

RG7314 repeat doses + intranasal AVP single dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)
• Participation in an investigational drug study within 90 days prior to randomization
• Donation or loss of blood over 500 mL within three months prior to randomization
• Chronic rhinitis, allergic rhinitis, nasal polyps or any other nasal pathology that may affect the absorption of intranasal AVP according to investigator judgment
• Concomitant disease, condition or treatment which might interfere with the conduct of the study, or what would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Unwilling or unable to comply with the following lifestyle guidelines: (1) participants will abstain from alcohol for the entire study participation; (2) abstinence from any psychoactive agents or drugs of abuse for the duration of the study period; (3) participants should abstain from unusual strenuous exercise throughout the entire study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Leiden, , Netherlands

Countries

Netherlands

Other Identifiers

2014-000867-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP29412

Identifier Type: -

Identifier Source: org_study_id