Clinical trial NCT01995383: A Single Ascending Dose Study Investigating the Safety, Pharmacokinetics and Pharmacodynamics of RO6836191 in Healthy Male Volunteers.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atherosclerosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-11-26
Enrollment: 88
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 2: Area under the concentration-time curve (AUC)
timeFrame: Up to Day 35
measure: Part 2: Plasma aldosterone levels
timeFrame: Up to 2 days after drug administration
measure: Part 2: Urine aldosterone levels
timeFrame: Up to 3 days after drug administration
measure: Part 1: Plasma aldosterone levels
timeFrame: Up to Day 5
measure: Part 1: Urine aldosterone levels
timeFrame: Up to Day 3
measure: Part 2: Incidence of AEs
timeFrame: Up to 12 weeks
measure: Parts 1: Incidence of adverse events (AE)
timeFrame: Until Day 21
Secondary outcomes:
measure: Part 2: Volume of distribution after intravenous administration
timeFrame: Days 28-37
Other outcomes:
Locations:
city: Marlton
country: United States
state: New Jersey
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.