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

NCT02633709 | Completed Phase 1

• 2 other identifiers: BP298402015-004605-16
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants with Adverse Events (AEs)

  Parts 1 and 2: Up to 21 days after last dose of study drug. Part 3: Up to 28 days after last dose of study drug.

• Percentage of Participants with Laboratory Test Abnormalities

  Parts 1 and 2: Up to 21 days after last dose of study drug. Part 3: Up to 28 days after last dose of study drug.

• Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Vital Signs and Electrocardiograms (ECGs)

  Parts 1 and 2: Up to 21 days after last dose of study drug. Part 3: Up to 28 days after last dose of study drug.

• Percentage of Participants with Clinically Significant Changes in Ophthalmological Assessments

  Part 1: Up to 26 weeks; Part 2 (Treatment Period [TP] 1 and 2): Up to 29 weeks; Part 3 (TP 1, 2): Up to 30 weeks

Secondary Outcomes (17)

• Maximum Observed Plasma Concentration (Cmax)

  Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

• Time to Maximum Plasma Concentration (Tmax)

  Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

• Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast)

  Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

• Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf)

  Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

• Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t)

  Parts 1 and 2: Up to Day 21; Part 3: Up to Day 28

Study Arms (5)

Part 1: Single Ascending Dose: Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Part 1: Single Ascending Dose: Risdiplam

EXPERIMENTAL

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

Drug: Risdiplam

Part 2: Food Effect: Fasted-Fed

EXPERIMENTAL

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.

Drug: Risdiplam

Part 2: Food Effect: Fed-Fasted

EXPERIMENTAL

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.

Drug: Risdiplam

Part 3: Itraconazole Interaction

EXPERIMENTAL

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.

Drug: Itraconazole; Drug: Risdiplam

Interventions

Itraconazole DRUG

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

Also known as: Sporanox®

Part 3: Itraconazole Interaction

Placebo OTHER

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

Part 1: Single Ascending Dose: Placebo

Risdiplam 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).

Also known as: RO7034067

Part 1: Single Ascending Dose: Risdiplam; Part 2: Food Effect: Fasted-Fed; Part 2: Food Effect: Fed-Fasted; Part 3: Itraconazole Interaction

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Pra International Group B.V

Groningen, 9728 NZ, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 37148485 DERIVED

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Itraconazole; Risdiplam

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 17, 2015
• Study Start: January 7, 2016
• Primary Completion: August 4, 2016
• Study Completion: August 4, 2016
• Last Updated: October 4, 2018

Record last verified: 2018-10

Locations

NL (1)