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

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ClinicalTrials.gov Identifier: NCT03988907
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Drug: Risdiplam Drug: Midazolam Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 18, 2019
Estimated Primary Completion Date : October 18, 2019
Estimated Study Completion Date : October 18, 2019


Arm Intervention/treatment
Experimental: Part 1
Participants will receive a dose of 5 milligram (mg) risdiplam once daily (QD) for 14 consecutive days
Drug: Risdiplam
Part 1: a dose of 5 milligram (mg) risdiplam QD ; Part 2: precise dose will be based on Part 1 results

Experimental: Part 2
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)
Drug: Risdiplam
Part 1: a dose of 5 milligram (mg) risdiplam QD ; Part 2: precise dose will be based on Part 1 results

Drug: Midazolam
single dose administration of 2 mg midazolam




Primary Outcome Measures :
  1. Plasma Concentration of Midazolam Alone and in Combination with Risdiplam [ Time Frame: Day 1 to Day 20 ]
  2. Plasma Concentration of Midazolam Metabolite Alone and in Combination with Risdiplam [ Time Frame: Day 1 to Day 20 ]

Secondary Outcome Measures :
  1. 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 ]
    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

  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 ]
    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

  3. Plasma Concentration of Risdiplam Metabolite Following Multiple Oral Doses [ Time Frame: Day 1 to Day 20 ]
  4. Plasma Concentration of Risdiplam Following Multiple Oral Doses [ Time Frame: Day 1 to Day 20 ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03988907


Contacts
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Contact: Reference Study ID Number: BP41361 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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United States, Texas
Covance Research Unit - Dallas Recruiting
Dallas, Texas, United States, 75247
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03988907     History of Changes
Other Study ID Numbers: BP41361
First Posted: June 18, 2019    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action