A Drug-drug Interaction Study With Risdiplam Multiple Dose and Midazolam in Healthy Participants

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03988907
• Date of registration: 14/06/2019
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Drug-drug Interaction Study With Risdiplam Multiple Dose and Midazolam in Healthy Participants
• Scientific title: A Phase I, 2-Part, Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Risdiplam and the Effect of Risdiplam on the Pharmacokinetics of Midazolam Following Oral Administration in Healthy Participants
• Date of first enrolment: June 18, 2019
• Target sample size: 35
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03988907
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Healthy participants as defined by the Investigator

- A body mass index (BMI) of 18.0 to 32.0 kg/m2

- Use of adequate contraception methods during the treatment period and until 4 months
after last study drug administration. Males must refrain from donating sperm during
this same period

- Willingness and ability to complete all aspects of the study

Exclusion Criteria:

- Concomitant disease or condition that could interfere with, or treatment of which
might interfere with, the conduct of the study

- 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

- History or presence of clinically significant ECG abnormalities or cardiovascular
disease

- History of malignancy in the past 5 years

- Positive result on human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus, or
hepatitis C virus

- Donation of blood or blood products for transfusion

- Participation in an investigational drug medicinal product or medical device study
within 90 days prior to Screening

- Any clinically significant history of hypersensitivity or allergic reactions

- History of hypersensitivity to midazolam or any other benzodiazepine or its
formulation ingredients

For Part 2 participants:

- History of acute angle glaucoma



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Drug: Midazolam

Drug: Risdiplam

Primary Outcome(s)

Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam [Time Frame: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose]

Part 2: Cmax of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam [Time Frame: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose]

Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Midazolam Alone and in Combination With Risdiplam [Time Frame: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose]

Part 2: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone and in Combination With Risdiplam [Time Frame: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose]

Part 2: AUCinf of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam [Time Frame: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose]

Part 2: AUClast of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam [Time Frame: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose]

Secondary Outcome(s)

Part 1: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses [Time Frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 2 to Day 13: Predose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose]

Part 1 and Part 2: Percentage of Participants With Adverse Events After Administration of Multiple Doses of Risdiplam [Time Frame: Day 1 to Day 20 and up to 10+/-2 Days Post Final Dose or Early Termination]

Part 2: AUCtau of Risdiplam and M1 Risdiplam Following Multiple Oral Doses [Time Frame: Day 3: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 4 to Day 15: Predose; Day 16: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose]

Part 2: Percentage of Participants With Adverse Events After Midazolam Administration Alone and in Combination With Risdiplam [Time Frame: Day 1 to Day 20 and up to 10+/-2 Days Post Final Dose or Early Termination]

Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Risdiplam and Its Metabolite (M1) Following Multiple Oral Doses [Time Frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 2 to Day 13: Predose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose]

Part 1: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses [Time Frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 2 to Day 13: Predose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose]

Part 2: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses [Time Frame: Day 3: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 4 to Day 15: Predose; Day 16: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose]

Part 2: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses [Time Frame: Day 3: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 4 to Day 15: Predose; Day 16: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose]

Secondary ID(s)

BP41361

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/10/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03988907