Bioavailability and Bioequivalence of Two Risdiplam Tablets in Healthy Participants

NCT04718181 | Completed Phase 1 FDA Drug

• 1 other identifier: BP42066
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 4

Brief Summary

The study is a randomized, single oral dose, crossover study in up to three parts to investigate the relative bioavailability and bioequivalence of two different formulations of risdiplam 5 mg (dispersible tablets) versus the current risdiplam oral solution formulation in healthy male and female participants. The effect of food on these two dispersible tablets and the current oral solution will be studied, as well as the effect of omeprazole on the dispersible tablets.

Conditions

Muscular Atrophy, Spinal

Outcome Measures

Primary Outcomes (4)

• Part 1: Plasma Concentration of Risdiplam in Cohorts A and B

  Day 1 to Day 7 in Periods 1-5

• Part 1: Plasma Concentration of Risdiplam in Fed and Fasted States in Cohort E

  Day 1 to Day 7 in Period 1 and Period 2

• Part 1: Plasma Concentration of Risdiplam in Cohorts C and D

  Period 1: Day 1 to Day 7; Period 2: Day 1 to Day 13

• Parts 2 and 3: Plasma Concentration of Risdiplam

  Day 1 to Day 11 in Periods 1-4

Secondary Outcomes (1)

• Percentage of Participants with Adverse Events and Serious Adverse Events

  Part 1: up to Day 20 in Periods 1-2, up to Day 14 in Periods 3-5; Parts 2 and 3: up to Day 11 in Periods 1-4

Study Arms (3)

Part 1

EXPERIMENTAL

Cohort A+B: participants will receive, in a five-period crossover way, a single oral dose of risdiplam oral solution 5 mg in fasted state and thereafter risdiplam/F21 or F22 dispersible tablet 5 mg as tablet in fasted and fed states; tablet dispersed in water in fasted and fed states, with a 14-day wash-out period in between the single-dose administrations. Cohort C+D: participants will receive, in a two-period fixed sequence design, a single dose of risdiplam/F21 or F22 dispersible tablet 5 mg in fasted state and omeprazole 40 mg once daily for 7 days + a single dose of risdiplam/F21 or F22 dispersible tablet 5 mg in fasted state, on the 7th day of omeprazole. There will be a 14-day wash-out between the two treatment periods. Cohort E: participants will receive, in a two-period crossover design, a single oral dose of risdiplam oral solution 5 mg in fasted and fed states, with a 14-day wash-out period in between the single-dose administrations.

Drug: risdiplam; Drug: omeprazole

Part 2 (optional)

EXPERIMENTAL

Group 1: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F21) as swallowed tablet in both fed and fasted states. Group 2: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F21) as tablet dispersed in water in both fed and fasted states.

Drug: risdiplam

Part 3 (optional)

EXPERIMENTAL

Group 1: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F22) as swallowed tablet in both fed and fasted states. Group 2: participants will receive, in four-period crossover design, a single oral dose of risdiplam oral solution 5 mg in both fed and fasted states and the selected dispersible tablet (F22) as tablet dispersed in water in both fed and fasted states.

Drug: risdiplam

Interventions

risdiplam DRUG

Risdiplam will be administered orally at a single dose of 5 mg in different formulations. Dispersible tablet formulations (F21/F22) will be administered as swallowed tablet or as tablet dispersed in water. The powder for constitution to an oral solution will be administered as an oral solution constituted with purified water.

Also known as: Evrysdi

Part 1; Part 2 (optional); Part 3 (optional)

omeprazole DRUG

Omeprazole will be administered orally as a capsule at a dose of 40 mg per day

Also known as: Non-investigational medicinal product

Part 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A body mass index (BMI) of 18.0 to 32.0 kg/m2
• Male participants, whose partners are women of childbearing potential (WOCBP) or pregnant, must remain abstinent or use adequate contraception methods (both male participant and non-pregnant WOCBP partner) during the treatment period and until 4 months after the last dose of risdiplam or for pregnant female partners during the treatment period and until 28 days after the last dose of risdiplam. Males must refrain from donating sperm during the treatment period and until 4 months after the last dose of risdiplam.
• Willingness and ability to complete all aspects of the study
• A female subject is eligible to participate if she is a woman of non-childbearing potential (WONCBP)

You may not qualify if:

• History of any clinically significant gastrointestinal (Gl), renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, or allergic disease, metabolic disorder, cancer or cirrhosis
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study, including but not limited to the following: Any major illness within 1 month before screening or any febrile illness within 1 week prior to screening and up to first study drug administration
• History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs
• History or presence of clinically significant ECG abnormalities (at Screening only) or cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death)
• History of malignancy in the past 5 years
• Confirmed systolic blood pressure (BP) \>140 or \<90 mmHg, and diastolic BP \>90 or \<50 mmHg at Screening only
• Confirmed resting heart rate \>100 or \<40 beats per minute (bpm) at Screening only
• Clinically significant abnormalities in laboratory test results including hematology, chemistry panel, and urinalysis
• Positive result on human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus, or hepatitis C virus (serology) tests at Screening only
• Any suspicion or history of alcohol abuse and/or any history or suspicion of regular consumption/addiction of drugs of abuse within 2 years prior to study drug administration or a positive drug screen test as performed at Screening
• Any consumption of tobacco- or nicotine-containing products from 1 month before Check-in until the end of the study
• Donation of blood or blood products for transfusion over 500 mL within 3 months prior to first study drug administration and for the duration of the study
• Currently enrolled in a clinical study involving another investigational product or in any other type of medical research, or have received the last dose of another investigational product within the last 90 days from clinic check-in (Day -1).
• Use of any prescription (other than hormone replacement therapy) or over-the-counter medications, including herbals and vitamins, within 30 days prior to Check-in
• Any clinically significant history of hypersensitivity or allergic reactions, either spontaneous or following study drug administration, or exposure to food or environmental agents

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (4)

Daytona Beach Clinical Rsch Unit

Daytona Beach, Florida, 32117, United States

Location

QPS- Springfield

Springfield, Missouri, 65802, United States

Location

Dallas Clinical Research Unit

Dallas, Texas, 75247, United States

Location

Covance Clinical Research Unit, Inc

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Risdiplam; Omeprazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 22, 2021
• Study Start: February 1, 2021
• Primary Completion: January 28, 2023
• Study Completion: January 28, 2023
• Last Updated: March 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)