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NCT01380184

Pharmacokinetics of Ridaforolimus (MK-8669) in Chinese Participants (MK-8669-059)

Completed Phase 1 Results posted Last updated 19 April 2019
What this trial tests

Phase 1 trial testing ridaforolimus in Cancer, Advanced in 15 participants. Completed in 5 April 2012.

Timeline
5 July 2011
Primary endpoint
20 October 2011
5 April 2012

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment15
Start date5 July 2011
Primary completion20 October 2011
Estimated completion5 April 2012

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, any sex, with Cancer, Advanced. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) Secondary · From first dose up to 30 days after last dose (Up to 26 weeks)

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 clinica

Clinical & Laboratory AEs
GroupValue95% CI
Ridaforolimus 40 mg15
Drug-related AEs
GroupValue95% CI
Ridaforolimus 40 mg15
Serious AEs (SAEs)
GroupValue95% CI
Ridaforolimus 40 mg4
Lag Time (Tlag) of Ridaforolimus: Day 1 Primary · Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 is 19 days

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.

GroupValue95% CI
Ridaforolimus 40 mg2.000.97 – 8.07
Area Under the Curve From 0 to Infinity (AUC0-∞) of Ridaforolimus: Cycle 1 (Cycle 1 is 19 Days) Primary · Cycle 1: Predose on Day 1 and at various time points through to 24 hours postdose on Day 19; 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-∞.

GroupValue95% CI
Ridaforolimus 40 mg36483044 – 4372
Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Ridaforolimus: Day 1, Day 19 Primary · 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

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 d

Day 1
GroupValue95% CI
Ridaforolimus 40 mg18461361 – 2503
Day 19
GroupValue95% CI
Ridaforolimus 40 mg20141485 – 2731
Maximum Concentration (Cmax) of Ridaforolimus: Day 1, Day 19 Primary · 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

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.

Day 1
GroupValue95% CI
Ridaforolimus 40 mg210150 – 295
Day 19
GroupValue95% CI
Ridaforolimus 40 mg167119 – 234
Concentration at 24 Hours (C24hr) of Ridaforolimus: Day 1, Day 19 Primary · 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

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.

Day 1
GroupValue95% CI
Ridaforolimus 40 mg34.826.0 – 46.8
Day 19
GroupValue95% CI
Ridaforolimus 40 mg49.736.4 – 67.7
Time to Maximum Concentration (Tmax) of Ridaforolimus: Day 1, Day 19 Primary · 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

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.

Day 1
GroupValue95% CI
Ridaforolimus 40 mg4.032.00 – 7.97
Day 19
GroupValue95% CI
Ridaforolimus 40 mg4.000.00 – 6.00
Apparent Terminal Half-life (t1/2) of Ridaforolimus: Cycle 1 (Cycle 1 is 19 Days) Primary · Cycle 1: Predose on Day 1 and at various time points through to 24 hours postdose on Day 19; 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.

GroupValue95% CI
Ridaforolimus 40 mg52.940.2 – 65.6

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose up to 30 days after last dose (Up to 26 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ridaforolimus 40 mg
Serious: 4/15 (27%)
Deaths: 3/15

Serious adverse events (3 terms)

ReactionSystemRidaforolimus 40 mg
Neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progressionGeneral disorders
Tracheal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (39 terms — click to expand)

ReactionSystemRidaforolimus 40 mg
StomatitisGastrointestinal disorders
ProteinuriaRenal and urinary disorders
White blood cell count decreasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
Gamma-glutamyltransferase increasedInvestigations
AnaemiaBlood and lymphatic system disorders
Blood cholesterol increasedInvestigations
Platelet count decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
FatigueGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Periodontal diseaseGastrointestinal disorders
OedemaGeneral disorders
ParonychiaInfections and infestations
Urinary tract infectionInfections and infestations
Neutrophil count decreasedInvestigations
Weight decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HypertriglyceridaemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HaematuriaRenal and urinary disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Neoplasm malignant, Disease progression, Tracheal cancer.

Data from ClinicalTrials.gov NCT01380184 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immunometabolism in cancer: basic mechanisms and new targeting strategy.
    Su R, Shao Y, Huang M, Liu D, et al · · 2024 · cited 28× · PMID 38755125 · DOI 10.1038/s41420-024-02006-2
  2. Prostate cancer stem cells and their targeted therapies.
    Su H, Huang L, Zhou J, Yang G. · · 2024 · cited 5× · PMID 39175878 · DOI 10.3389/fcell.2024.1410102
  3. A phase I study of ridaforolimus in adult Chinese patients with advanced solid tumors.
    Liu L, Zhang W, Li W, Lv F, et al · · 2013 · cited 5× · PMID 23829943 · DOI 10.1186/1756-8722-6-48

Verify or expand the search:

Other trials of ridaforolimus

Trials testing the same drug.

Other recruiting trials for Cancer, Advanced

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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