start date: February 1, 2021
estimated completion: April 18, 2022
last updated: December 16, 2021
phase of development:
Phase 1
size / enrollment: 268
study description: Part 1 of the study is an exploratory comparison of the relative oral bioavailability of the two dispersible tablets versus risdiplam powder for oral solution as the reference. The effect of food on the bioavailability of the two dispersible tablets will be assessed by comparing fed and fasted states in a five-way crossover manner. It will also be assessed whether antacids (omeprazole) have an impact on the bioavailability of the dispersible tablets in a two-way crossover manner. The food effect on the risdiplam oral solution will also be assessed by comparing fed and fasted states in a two-way crossover manner.
In Part 2, based on the data obtained in Part 1 and provided data support further evaluation, a bioequivalence assessment and a food-effect evaluation will be conducted in two groups with the selected dispersible tablet formulation. Each group will randomly receive, in a three-way crossover, a single dose of risdiplam oral solution 5 mg in fasted state, and a single dose of the selected dispersible tablet in both fed and fasted states.
In Part 3, provided Part 1 data support further evaluation of the second formulation, the second formulation may be assessed for bioequivalence in the same way as described in Part 2.
Enrollment of the same participant in more than one cohort or group will not be permitted regardless of the study part.
primary outcomes:
- Plasma Concentrations of Risdiplam in Cohorts A and B
- Day 1 to Day 7 in Periods 1-5
secondary outcomes:
- Plasma Concentrations of Risdiplam in Fed and Fasted States in Cohort E
Day 1 to Day 7 in Period 1 and Period 2
- Plasma Concentrations of Risdiplam in Cohorts C and D
Period 1: Day 1 to Day 7; Period 2: Day 1 to Day 13
- Percentage of Participants with Adverse Events and Serious Adverse Events
Day 1 to Day 11
inclusion criteria:
• Eligible Ages: 18 - 55
• Eligible Sexes: all
Inclusion Criteria:
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 during the treatment period and until 4 months after the last dose of risdiplam for non-pregnant WOCBP partners or during the treatment period and until 28 days after the last dose of risdiplam for pregnant female partners. 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)
exclusion criteria: Criteria:
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
Surgical history of the GI tract affecting gastric motility or altering the GI tract (with the exception of uncomplicated appendectomy and hernia repair; a cholecystectomy is exclusionary)
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 screening 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
History of hypersensitivity to any of the excipients in the formulation of the study drug
Participants under judicial supervision, guardianship, or curatorship
English
Spanish
