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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Atherosclerosis

Intervention / Treatment
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* Other: LS followed by NS diet condition
* Other: NS followed by LS diet condition
* Drug: Placebo
* Drug: Placebo
* Drug: RO6836191
* Drug: RO6836191
* Drug: RO6836191


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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