Phase 1
Completed N=35
A Drug-drug Interaction Study With Risdiplam Multiple Dose and Midazolam in Healthy Participants
Source: ClinicalTrials.gov NCT03988907 ↗Enrolled (actual)
35
Serious AEs
0.0%
Results posted
Oct 2020
Primary outcomePrimary: Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam — 22.6; 25.1 h*ng/mL
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam |
22.6; 25.1 | — |
| PRIMARY 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 |
19.9; 22.0 | — |
| PRIMARY Part 2: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone and in Combination With Risdiplam |
7.65; 8.96 | — |
| PRIMARY Part 2: AUCinf of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam |
8.66; 9.41 | — |
| PRIMARY Part 2: AUClast of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam |
7.75; 9.43 | — |
| PRIMARY Part 2: Cmax of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam |
3.18; 4.10 | — |
| SECONDARY 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 |
404; 78.4; 1250; 349 | — |
| SECONDARY Part 1: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses |
399; 78.2; 3160; 929 | — |
| SECONDARY Part 1: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses |
25.9; 4.33; 78.6; 19.1 | — |
| SECONDARY Part 2: AUCtau of Risdiplam and M1 Risdiplam Following Multiple Oral Doses |
613; 131; 1730; 504 | — |
| SECONDARY Part 2: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses |
597; 130; 4280; 1350 | — |
| SECONDARY Part 2: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses |
42.6; 7.33; 113; 30.5 | — |
| SECONDARY Part 2: Percentage of Participants With Adverse Events After Midazolam Administration Alone and in Combination With Risdiplam |
7.4; 7.7; 0.0; 0.0 | — |
| SECONDARY Part 1 and Part 2: Percentage of Participants With Adverse Events After Administration of Multiple Doses of Risdiplam |
25.0; 51.9; 0.0; 0.0 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT03988907). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.