Part 1 of the study will assess the pharmacokinetics, safety, and tolerability of ridaforolimus (MK-8669) after administration of single and multiple 40 mg doses in Chinese participants with advanced cancer. Part 2 of the study is optional; participants can continue to receive the study treatment in a weekly regimen of daily oral doses of ridaforolimus 40 mg for five consecutive days followed by two days off-treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
4 enteric-coated tablets, each containing 10 mg ridaforolimus, orally (total daily dose: 40 mg)
Lag Time (Tlag) of Ridaforolimus: Day 1
Tlag is the time taken for ridaforolimus to appear in systemic circulation following oral administration. The median and full range (minimum, maximum) for Tlag after a single dose of ridafolorlimus are presented.
Time frame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 is 19 days
Area Under the Curve From 0 to Infinity (AUC0-∞) of Ridaforolimus: Cycle 1 (Cycle 1 is 19 Days)
AUC0-∞ represents the total exposure to ridaforolimus and its average blood concentration multiplied by the total amount of time (extrapolated to infinity) that ridaforolimus was in the body. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric mean and back-transformed 95% confidence interval are presented for AUC0-∞.
Time frame: Cycle 1: Predose on Day 1 and at various time points through to 24 hours postdose on Day 19; Cycle 1 is 19 days
Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Ridaforolimus: Day 1, Day 19
AUC0-24hr represents the total exposure to ridaforolimus and its average blood concentration multiplied by the total amount of time (extrapolated to 24 hours) that ridaforolimus was in the body. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric means and back-transformed 95% confidence intervals after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented for AUC0-24hr.
Time frame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
Maximum Concentration (Cmax) of Ridaforolimus: Day 1, Day 19
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Cmax is the peak blood plasma concentration following a dose of ridaforolimus. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric means and back-transformed 95% confidence intervals after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented for Cmax.
Time frame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
Concentration at 24 Hours (C24hr) of Ridaforolimus: Day 1, Day 19
C24hr is the concentration of ridaforolimus in the blood 24 hours after a dose of ridaforolimus. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric means and back-transformed 95% confidence intervals after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented for C24hr.
Time frame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
Time to Maximum Concentration (Tmax) of Ridaforolimus: Day 1, Day 19
Tmax is the time at which the Cmax of ridaforolimus is reached. The medians and ranges (minimum, maximum) for Tmax after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented.
Time frame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
Apparent Terminal Half-life (t1/2) of Ridaforolimus: Cycle 1 (Cycle 1 is 19 Days)
t½ is the time that it takes for the concentration of ridaforolimus in the body to decrease by half. The (harmonic) means and 95% confidence intervals for t1/2 after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented.
Time frame: Cycle 1: Predose on Day 1 and at various time points through to 24 hours postdose on Day 19; Cycle 1 is 19 days
Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs)
A laboratory AE (LAE) is defined as any unfavorable \& unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE (CAE) is defined similarly but also includes changes in structure or function of the body. Serious AEs (SAEs) are those that result in one or more of the pre-specified outcome(s) that meet the criteria of seriousness, including death, life-threatening, significant disability, or hospitalization, etc. Drug-relatedness was determined by the investigator based on clinical judgement.
Time frame: From first dose up to 30 days after last dose (Up to 26 weeks)