A Single Ascending Dose Study Investigating the Safety, Pharmacokinetics and Pharmacodynamics of RO6836191 in Healthy Male Volunteers.

A Single Oral Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO6836191 in Healthy Male Subjects Including a Single Intravenous Microdose of RO6836191

This single-center, randomized, placebo-controlled, double-blind study will assess the safety, pharmacokinetics and pharmacodynamics of RO6836191 in healthy male volunteers in two parts. Part 1 will assess the safety of oral single ascending doses of RO6836191 compared to placebo in fasted volunteers. In Part 2, participants will be given two single oral doses of RO6836191 or placebo under low or normal-salt diet conditions. A subset of these participants will subsequently receive a single IV dose of RO6836191 for further analysis.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Placebo; Drug: RO6836191; Drug: RO6836191; Drug: RO6836191; Other: LS followed by NS diet condition; Other: NS followed by LS diet condition

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Marlton, New Jersey, United States, 08053

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers, aged 18 to 45 years old.
• No active or chronic disease following a detailed medical and surgical history and complete physical examination.
• A BMI between 18 to 30 kg/m2 inclusive.
• Use of a highly effective form of birth control for the duration of the study and until 90 days after the last dose.

Exclusion Criteria:

• Any clinically relevant current or history of conditions or illnesses.
• Clinically significant symptoms of infection within 5 days of the first dosing day or a history of recurrent infections.
• Any suspicion or history of alcohol abuse and/or consumption of other drugs of abuse.
• Smokers unable or unwilling to restrict to 5 cigarettes daily during the study and to not smoke during the stay at the clinic.
• Any cardiac abnormalities.
• Blood donation over 450 mL within three months prior to screening.
• Participation in an investigational drug or device study within 3 months prior to dosing.
• Corticosteroid use within 3 months prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1: Placebo (PL)	Drug: Placebo; Single oral administrations; Drug: Placebo; 2 single oral administrations
Experimental: Part 1: Single Ascending Doses (SAD) of RO6836191	Drug: RO6836191; Orally administered, single ascending doses; Drug: RO6836191; 2 single oral doses; Drug: RO6836191; Intravenous administration
Placebo Comparator: Part 2: PL: Low-salt (LS) followed by normal-salt (NS) diet	Drug: Placebo; Single oral administrations; Drug: Placebo; 2 single oral administrations; Drug: RO6836191; Orally administered, single ascending doses; Drug: RO6836191; 2 single oral doses; Drug: RO6836191; Intravenous administration; Other: LS followed by NS diet condition; LS diet period followed by NS diet period
Placebo Comparator: Part 2: PL: NS followed by LS diet	Drug: Placebo; Single oral administrations; Drug: Placebo; 2 single oral administrations; Drug: RO6836191; Orally administered, single ascending doses; Drug: RO6836191; 2 single oral doses; Drug: RO6836191; Intravenous administration; Other: NS followed by LS diet condition; NS diet period followed by LS diet period
Experimental: Part 2: RO6836191: LS followed by NS diet	Drug: RO6836191; Orally administered, single ascending doses; Drug: RO6836191; 2 single oral doses; Drug: RO6836191; Intravenous administration; Other: LS followed by NS diet condition; LS diet period followed by NS diet period
Experimental: Part 2: RO6836191: NS followed by LS diet	Drug: RO6836191; Orally administered, single ascending doses; Drug: RO6836191; 2 single oral doses; Drug: RO6836191; Intravenous administration; Other: NS followed by LS diet condition; NS diet period followed by LS diet period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 2: Area under the concentration-time curve (AUC)	Up to Day 35
Part 2: Plasma aldosterone levels	Up to 2 days after drug administration
Part 2: Urine aldosterone levels	Up to 3 days after drug administration
Part 1: Plasma aldosterone levels	Up to Day 5
Part 1: Urine aldosterone levels	Up to Day 3
Part 2: Incidence of AEs	Up to 12 weeks
Parts 1: Incidence of adverse events (AE)	Until Day 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 2: Volume of distribution after intravenous administration	Days 28-37

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Bogman K, Schwab D, Delporte ML, Palermo G, Amrein K, Mohr S, De Vera Mudry MC, Brown MJ, Ferber P. Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral Inhibitor of Aldosterone Synthase (CYP11B2). Hypertension. 2017 Jan;69(1):189-196. doi: 10.1161/HYPERTENSIONAHA.116.07716. Epub 2016 Nov 21.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: November 20, 2013
• First Submitted That Met QC Criteria: November 25, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Estimate): November 4, 2016
• Last Update Submitted That Met QC Criteria: November 3, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: WP28586