A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Risdiplam (RO7034067) in Healthy Japanese Participants

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03040635
• Other study ID #: NP39625
• Status: Completed
• Phase: Phase 1
• Start date: March 22, 2017
• Est. completion date: October 2, 2017

Study information

• Verified date: October 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2, 2017
• Est. primary completion date: October 2, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Risdiplam
Single oral doses of Risdiplam will be administered on Day 1.
• Placebo
Single oral doses of Risdiplam matching placebo will be administered on Day 1.

Locations

Country	Name	City	State
United States	Collaborative Neuroscience Network, Inc.	Garden Grove	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Risdiplam		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
Primary	Time to Maximum Plasma Concentration (Tmax) of Risdiplam		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
Primary	Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of Risdiplam		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
Primary	Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Risdiplam		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
Primary	Area Under the Plasma Concentration-Time Curve up to Time t (AUC0-t) of Risdiplam		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
Primary	Apparent Terminal Half-Life (t1/2) of Risdiplam		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
Primary	Apparent Oral Clearance (CL/F) of Risdiplam		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
Primary	Apparent Oral Volume of Distribution (Vz/F) of Risdiplam		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
Primary	Cumulative Amount Excreted Unchanged into Urine (Ae) of Risdiplam		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)
Primary	Renal Clearance (CLR) of Risdiplam		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)
Primary	Fraction of Dose Excreted Unchanged Renally (Fe) of Risdiplam		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)
Primary	Percentage of Participants with Adverse Events (AEs)		Up to approximately 7 weeks
Secondary	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		Days -1, 1, 2, 3, 4, 6
Secondary	Change from Baseline in mRNA Levels of Paired Box (PAX) Genes in Blood		Days -1, 1, 2, 3, 4, 6
Secondary	Change from Baseline in SMN Protein Levels in Blood		Day -1, follow-up visit (Day 21)