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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
Collaborative Neuroscience Network, Inc.
Garden Grove, California, United States
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
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
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
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
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
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
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
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
Cumulative Amount Excreted Unchanged into Urine (Ae) of Risdiplam
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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)
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)
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)
Percentage of Participants with Adverse Events (AEs)
Time frame: Up to approximately 7 weeks
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
Change from Baseline in mRNA Levels of Paired Box (PAX) Genes in Blood
Time frame: Days -1, 1, 2, 3, 4, 6
Change from Baseline in SMN Protein Levels in Blood
Time frame: Day -1, follow-up visit (Day 21)