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

NCT ID: NCT02633709

Last Updated: 2018-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-07
• Study Completion Date: 2016-08-04

Brief Summary

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.

Conditions

Spinal Muscular Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: Single Ascending Dose: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

In Part 1 of the study matching oral placebo will be administered once on Day 1.

Part 1: Single Ascending Dose: Risdiplam

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

Group Type: EXPERIMENTAL

Risdiplam

Intervention Type: DRUG

Single ascending oral doses of Risdiplam will be administered on Day 1 of Part 1. In Part 2 a single dose of Risdiplam will be once administered under fasted and once under fed conditions. In Part 3 a single dose of Risdiplam will be once administered alone (Period 1) and once concomitantly to itraconazole (Period 2).

Part 2: Food Effect: Fasted-Fed

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.

Group Type: EXPERIMENTAL

Risdiplam

Intervention Type: DRUG

Single ascending oral doses of Risdiplam will be administered on Day 1 of Part 1. In Part 2 a single dose of Risdiplam will be once administered under fasted and once under fed conditions. In Part 3 a single dose of Risdiplam will be once administered alone (Period 1) and once concomitantly to itraconazole (Period 2).

Part 2: Food Effect: Fed-Fasted

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.

Group Type: EXPERIMENTAL

Risdiplam

Intervention Type: DRUG

Single ascending oral doses of Risdiplam will be administered on Day 1 of Part 1. In Part 2 a single dose of Risdiplam will be once administered under fasted and once under fed conditions. In Part 3 a single dose of Risdiplam will be once administered alone (Period 1) and once concomitantly to itraconazole (Period 2).

Part 3: Itraconazole Interaction

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.

Group Type: EXPERIMENTAL

Itraconazole

Intervention Type: DRUG

Itraconazole will be administered as an oral 200 mg dose twice daily from Day 1 to Day 8 in Part 3.

Risdiplam

Intervention Type: DRUG

Single ascending oral doses of Risdiplam will be administered on Day 1 of Part 1. In Part 2 a single dose of Risdiplam will be once administered under fasted and once under fed conditions. In Part 3 a single dose of Risdiplam will be once administered alone (Period 1) and once concomitantly to itraconazole (Period 2).

Interventions

Itraconazole

Itraconazole will be administered as an oral 200 mg dose twice daily from Day 1 to Day 8 in Part 3.

Intervention Type: DRUG

Placebo

In Part 1 of the study matching oral placebo will be administered once on Day 1.

Intervention Type: OTHER

Risdiplam

Single ascending oral doses of Risdiplam will be administered on Day 1 of Part 1. In Part 2 a single dose of Risdiplam will be once administered under fasted and once under fed conditions. In Part 3 a single dose of Risdiplam will be once administered alone (Period 1) and once concomitantly to itraconazole (Period 2).

Intervention Type: DRUG

Other Intervention Names

Sporanox®; RO7034067

Eligibility Criteria

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

• 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

Pra International Group B.V

Groningen, , Netherlands

Countries

Netherlands

References

Cleary Y, Kletzl H, Grimsey P, Heinig K, Ogungbenro K, Silber Baumann HE, Frey N, Aarons L, Galetin A, Gertz M. Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children. Clin Pharmacokinet. 2023 Jun;62(6):891-904. doi: 10.1007/s40262-023-01241-7. Epub 2023 May 6.

Reference Type: DERIVED

PMID: 37148485 (View on PubMed)

Other Identifiers

2015-004605-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP29840

Identifier Type: -

Identifier Source: org_study_id