- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03040635
A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) in Healthy Japanese Participants
October 2, 2018 updated by: Hoffmann-La Roche
An Investigator/Subject Blind, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of RO7034067 in Healthy Japanese Subjects
This is a randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of Risdiplam in healthy Japanese participants.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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California
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Garden Grove, California, United States, 92845
- Collaborative Neuroscience Network, Inc.
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Participants of Japanese origin, with Japanese parents (for the provisional Caucasian cohort, participants must be male or female Caucasians with 4 Caucasian grand-parents)
- Healthy participants. Healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including ophthalmological examination, vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis
- A body mass index (BMI) between 18 to 30 kilograms per square meter (kg/m^2) inclusive
- Male participants must agree to use a barrier method of contraception from dosing until completion of the study and for 4 months thereafter
- Female participants must be either surgically sterile or post-menopausal
Exclusion Criteria:
- Medical history of cardiovascular disease, renal disease, liver disease, digestive system disease, blood dyscrasia, immunologic disease, diseases of the nervous system, endocrine disease, metabolic disease, lung disease, or with anamnesis and obstacles in kidney, liver, or cardiopulmonary function
- Participants with any clinically significant eye pathology
- Laboratory test (hematology, biochemistry, physical examination or vital signs) values outside the institutional normal range and rated as clinically significant abnormal at screening
- Any clinically significant abnormalities in ECG at screening
- Inherited long QT syndrome or known family history of arrhythmia
- Systolic blood pressure (SBP) higher than 140 millimeters of mercury (mmHg) or below 90 mmHg, and/or diastolic blood pressure (DBP) higher than 90 mmHg or below 50 mmHg in the supine position, as assessed at screening
- Positive result for human immunodeficiency virus (HIV) antigen and antibody, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at screening
- Donation or loss of blood over 500 milliliters (mL) within three months prior to screening
- History of smoking more than 10 cigarettes a day. Participants who have quit smoking or who have reduced their daily cigarette smoking to 10 or less for more than one month prior to screening are allowed
- Daily consumption of food or drink containing a large amount of methylxanthine (caffeine, theophylline, theobromine)
- Present or past history of substance addiction, dependence or abuse, such as abuse of drugs or alcohol
- Concomitant or previous participation in any clinical trial either within 90 days or 5 half-lives of the investigational drug, whichever is longer, before administration of study drug in this study
- Use of prescribed medications which have systemic exposure within one week before enrolment
- Use of any concomitant drug during the study (including over-the-counter medication and medications used in dentistry)
- Inability to meet the study requirements in the opinion of the Investigator
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Risdiplam '2' Milligrams (mg)
A single dose of 2 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
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Single oral doses of Risdiplam will be administered on Day 1.
Other Names:
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Experimental: Risdiplam '6' mg
A single dose of 6 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
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Single oral doses of Risdiplam will be administered on Day 1.
Other Names:
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Experimental: Risdiplam '12' mg
A single dose of 12 mg Risdiplam will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
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Single oral doses of Risdiplam will be administered on Day 1.
Other Names:
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Placebo Comparator: Placebo
A single dose of placebo will be administered to all participants randomized to this arm under fasted conditions as an oral drinking solution on Day 1.
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Single oral doses of Risdiplam matching placebo will be administered on Day 1.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum Observed Plasma Concentration (Cmax) of Risdiplam
Time Frame: Pre-dose (0 hour [hr]), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
|
Pre-dose (0 hour [hr]), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
|
Time to Maximum Plasma Concentration (Tmax) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
|
Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
|
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Apparent Terminal Half-Life (t1/2) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Apparent Oral Clearance (CL/F) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Apparent Oral Volume of Distribution (Vz/F) of Risdiplam
Time Frame: Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Pre-dose (0 hr), 0.5, 1, 2, 3, 4, 4.5, 5, 6, 8, 10, 12, 24, 36, 48, 72, 120, 168, 264 hr postdose from Day 1
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Cumulative Amount Excreted Unchanged into Urine (Ae) of Risdiplam
Time Frame: Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
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Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
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Renal Clearance (CLR) of Risdiplam
Time Frame: Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
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Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
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Fraction of Dose Excreted Unchanged Renally (Fe) of Risdiplam
Time Frame: Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
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Pre-dose (0 hr), and 5 urine samples at different time-ranges postdose (0-6 hr, 6-12 hr, 12-24 hr, 24-48 hr, and 48-72 hr)
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Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 7 weeks
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Up to approximately 7 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change from Baseline in Splicing Modifications of Survival of Motor Neuron (SMN) Messenger Ribonucleic Acids (mRNAs), Including SMN1, SMN2 Full Length (FL), and SMNdelta7 mRNA in Blood In Vivo
Time Frame: Days -1, 1, 2, 3, 4, 6
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Days -1, 1, 2, 3, 4, 6
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Change from Baseline in mRNA Levels of Paired Box (PAX) Genes in Blood
Time Frame: Days -1, 1, 2, 3, 4, 6
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Days -1, 1, 2, 3, 4, 6
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Change from Baseline in SMN Protein Levels in Blood
Time Frame: Day -1, follow-up visit (Day 21)
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Day -1, follow-up visit (Day 21)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 22, 2017
Primary Completion (Actual)
October 2, 2017
Study Completion (Actual)
October 2, 2017
Study Registration Dates
First Submitted
February 1, 2017
First Submitted That Met QC Criteria
February 1, 2017
First Posted (Estimate)
February 2, 2017
Study Record Updates
Last Update Posted (Actual)
October 4, 2018
Last Update Submitted That Met QC Criteria
October 2, 2018
Last Verified
October 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NP39625
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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