A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) Given by Mouth in Healthy Volunteers

Roche

Status and phase: Completed; Phase 1

Conditions: Spinal Muscular Atrophy

Treatments: Other: Placebo; Drug: Risdiplam; Drug: Itraconazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT02633709

BP29840

2015-004605-16 (EudraCT Number)

Details and patient eligibility

About

The objective of this study is to assess the safety and tolerability of Risdiplam (RO7034067) in healthy people. The study will assess what the body does to Risdiplam (RO7034067) and what Risdiplam (RO7034067) does to the body. Risdiplam (RO7034067) will be given by mouth in gradually increasing doses. The data from this study will help to define the dose to further explore Risdiplam (RO7034067) in patients with Spinal Muscular Atrophy.

Enrollment: 33 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy men, aged 18 to 45 years of age, inclusive
• Body Mass Index (BMI) of 18 to 30 kilograms/meter square, inclusive

Exclusion criteria

• History or evidence of any medical condition potentially altering the absorption, metabolism or elimination of drugs
• History of malignancy in the past 5 years
• A history of clinically significant hypersensitivity (e.g. drugs, excipients) or allergic reactions
• Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first study drug administration
• History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
• Clinically significant abnormalities in laboratory test results
• Confirmed resting pulse rate (PR) greater than 100 or less than 40 bpm
• Confirmed systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg
• Positive result on HIV1 and HIV2, hepatitis C (HCV) or hepatitis B (HBV)
• History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, ophthalmological, dermatological, hematological or allergic disease, metabolic disorder, hypofertility, cancer or cirrhosis
• History or evidence of (neuro)muscular disorders
• Hypersensitivity to itraconazole, to any of the other ingredients, or to any other triazole antifungal
• Any other known contraindications to itraconazole

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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33 participants in 5 patient groups, including a placebo group

Part 1: Single Ascending Dose: Placebo

Placebo Comparator group

Description:

Participants will receive a single dose of matching placebo orally on Day 1 of Part 1.

Treatment:

Other: Placebo

Part 1: Single Ascending Dose: Risdiplam

Experimental group

Description:

Participants will receive a single ascending dose (SAD) of Risdiplam orally on Day 1 of Part 1.

Treatment:

Drug: Risdiplam

Part 2: Food Effect: Fasted-Fed

Experimental group

Description:

This arm consists of two periods. In Period 1 participants will receive one oral dose of Risdiplam in the fasted state on Day 1. In Period 2 participants will receive one oral dose of Risdiplam in the fed state on Day 1.

Treatment:

Drug: Risdiplam

Part 2: Food Effect: Fed-Fasted

Experimental group

Description:

This arm consists of two periods. In Period 1 participants will receive one oral dose of Risdiplam in the fed state on Day 1. In Period 2 participants will receive one oral dose of Risdiplam in the fasted state on Day 1.

Treatment:

Drug: Risdiplam

Part 3: Itraconazole Interaction

Experimental group

Description:

In Period 1 a single oral dose of Risdiplam will be administered. After a wash-out period in Period 2 participants will be administered oral doses of itraconazole twice daily from Day 1 to Day 8. On Day 4 participants will receive a single oral dose of Risdiplam in the fed state in combination with itraconazole.

Treatment:

Drug: Risdiplam

Drug: Itraconazole