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

Roche

Status and phase: Completed; Phase 1

Conditions: Spinal Muscular Atrophy

Treatments: Drug: Midazolam; Drug: Risdiplam

Study type: Interventional

Funder types: Industry

Identifiers

NCT03988907

BP41361

Details and patient eligibility

About

This will be a Phase I, 2-part, open-label, non-randomized study to investigate the safety, tolerability, and pharmacokinetics (PK) of a multiple-dosing regimen of risdiplam (Part 1) and the effect of risdiplam on the PK of midazolam (Part 2) following oral administration in healthy adult male and female participants.

Enrollment: 35 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

Part 1

Experimental group

Description:

Participants will receive a dose of 5 milligram (mg) risdiplam once daily (QD) for 14 consecutive days

Treatment:

Drug: Risdiplam

Part 2

Experimental group

Description:

All study participants will receive a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day QD treatment period with risdiplam will begin. The precise dose will be based on the results of Part 1, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam)

Treatment:

Drug: Risdiplam

Drug: Midazolam