Clinical trial · Interventional

A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037)

A Clinical Trial to Assess the Effect of Ridaforolimus (AP23573; MK-8669) on QTc Interval in Patients

NCT00874731CI-TRIAL-00038470completedPhase 1Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

To assess the potential for ridaforolimus to prolong the QTc interval (an effect on the electrical activity of the heart) in participants with advanced cancer. This study will be done in 2 parts. Part 1 (Pt 1) will evaluate the effect of a single 100 mg dose of ridaforolimus on QT interval in participants with advanced cancer. Fridericias's correction (QTcF) will be used. In Part 2 (Pt 2), participants will receive ridaforolimus at the current therapeutic dose (40 mg x 5 days).

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Metastatic or Locally Advanced Cancer	—	UNRESOLVED	—

Interventions

Interventions (3)

Intervention	Type	Mapped drug	Match
Placebo	Drug	—	UNRESOLVED
Ridaforolimus 100 mg	Drug	Ridaforolimus	ALIAS
Ridaforolimus 40 mg	Drug	Ridaforolimus	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg
description
\[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1. \[Pt 1, Day 2\]: Following completion of Part 1 / Day 1, participants received a single dose of ridaforolimus 100 mg (10 x 10 mg oral tablets) on Day 2 of Part 1. Following completion of Part 1 / Day 2, participants entered a washout period of ≥5 days before the first dose Part 2. \[Pt 2\]: Following completion of Part 1, participants received ridaforolimus 40 mg (4 x 10 mg oral tablets) given once daily (QD) for 5 consecutive days followed by 2 days off-drug.
interventionNames
1. Drug: Ridaforolimus 100 mg
2. Drug: Ridaforolimus 40 mg
3. Drug: Placebo

Primary outcomes (9)

measure
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours
timeFrame
Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1
description
The mean change from baseline (CFB) in QTcF at 0.5 hours post-dose was assessed. At baseline (pre-dose) and at 0.5 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

* Participant must have metastatic or locally advanced cancer which has failed to respond to standard therapy or no therapy exists.
* If the participant is a female, she must be postmenopausal or if she is of childbearing potential she must have blood pregnancy tests during the study and be willing to use 2 methods of contraception.
* If the participant is male and has female partners of child-bearing potential, he must agree to use a medically acceptable method of contraception during the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

* Participant has had chemotherapy, radiotherapy or biological therapy within the past 4 weeks.
* Participant is currently receiving other anti-cancer therapy.
* Participant is currently participating or has participated in a study with an investigation drug or device within the last 30 days.
* Participant has a primary central nervous system tumor or active brain metastases.
* Participant has a psychiatric disorder.
* Participant uses illegal drugs.
* Participant is pregnant or breastfeeding.
* Participant is known to be human immunodeficiency virus (HIV) positive.
* Participant has a known history of Hepatitis B or C.
* Participant has newly diagnosed diabetes.
* Participant has an active infection.
* Participant is unable to swallow capsules.
* Participant has received a blood transfusion with one week of study entry.
* Participant has a history of cardiac problems including heart failure, myocardial infarction, unstable angina, congestive heart failure or cardiac arrhythmia.
* Participant has a known sensitivity to the components of the study drug.
* Participant has not adequately recovered from any prior surgical procedure.
* Participant does not agree to refrain from use of herbal remedies and consumption of grapefruit juice for 2 weeks prior to and during the study.

References

Publications (1)

RESULTLush RM, Patnaik A, Sullivan D, Papadopoulos KP, Trucksis M, McCrea J, Cerchio K, Li X, Stroh M, Selverian D, Orford K, Ebbinghaus S, Agrawal N, Iwamoto M, Wagner JA, Tolcher A. A single supratherapeutic dose of ridaforolimus does not prolong the QTc interval in patients with advanced cancer. Cancer Chemother Pharmacol. 2012 Oct;70(4):567-74. doi: 10.1007/s00280-012-1942-7. Epub 2012 Aug 10. PMID 22878520