A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037 AM1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00874731
First received: March 31, 2009
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

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 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 participants will receive ridaforolimus at the current therapeutic dose (40 mg x 5 days).


Condition Intervention Phase
Metastatic or Locally Advanced Cancer.
Drug: Ridaforolimus 100 mg
Drug: Ridaforolimus 40 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Clinical Trial to Assess the Effect of Deforolimus (AP23573; MK-8669) on QTc Interval in Patients (Protocol 037)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Mean change from Baseline to 0.5 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 0.5 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 1 hour in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 1 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 2 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 2 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 3 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 3 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 4 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 4 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 6 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 6 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 8 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 8 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 10 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 10 ] [ Designated as safety issue: No ]
  • Mean change from Baseline to 24 hours in Fridericia's Correction to QT interval (QTcF) after single oral 100 mg dose of ridaforolimus versus placebo [ Time Frame: Baseline and Hour 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants experiencing adverse events [ Time Frame: In Part 1, Day 1 for placebo and Day 2 for ridaforolimus 100 mg; Part 2, from Day 1 up to 30 days after the last ridaforolimus 40 mg dose (up to approximately 1 year). ] [ Designated as safety issue: Yes ]
  • Number of Participants who Discontinued From Study Drug due to Adverse Events [ Time Frame: In Part 1, Day 1 for placebo and Day 2 for ridaforolimus 100 mg; Part 2, from Day 1 up to the last ridaforolimus 40 mg dose (up to approximately 1 year). ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: April 2009
Study Completion Date: April 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ridaforolimus

Part 1: Participants receive a single oral dose of placebo (10 tablets) on Day 1 and a single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) on Day 2. Each dose to be followed by 24 hours of Holter electrocardiogram (ECG) monitoring for QTc assessment.

Part 2 (optional): Participants receive a weekly regimen of daily oral doses of 40 mg ridaforolimus (4 x 10 mg tablets) for 5 consecutive days followed by 2 days off-drug.

Drug: Ridaforolimus 100 mg
Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2.
Other Names:
  • AP23573
  • MK-8669
  • deforolimus (until May 2009)
Drug: Ridaforolimus 40 mg
Part 2 (optional): Ridaforolimus 40 mg (4 x 10 mg tablets) was received on a regimen of daily oral doses for 5 consecutive days followed by 2 days off-drug.
Other Names:
  • AP23573
  • MK-8669
  • deforolimus (until May 2009)
Drug: Placebo
A single oral dose of placebo (10 x placebo tablets) was given on Day 1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have metastatic or locally advanced cancer which has failed to respond to standard therapy or no therapy exists
  • If the patient 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 patient 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:

  • Patient has had chemotherapy, radiotherapy or biological therapy within the past 4 weeks
  • Patient is currently receiving other anti-cancer therapy
  • Patient is currently participating or has participated in a study with an investigation drug or device within the last 30 days
  • Patient has a primary central nervous system tumor or active brain metastases
  • Patient has a psychiatric disorder
  • Patient uses illegal drugs
  • Patient is pregnant or breastfeeding
  • Patient is known to be human immunodeficiency virus (HIV) positive
  • Patient has a known history of Hepatitis B or C
  • Patient has newly diagnosed diabetes
  • Patient has an active infection
  • Patient is unable to swallow capsules
  • Patient has received a blood transfusion with one week of study entry
  • Patient has a history of cardiac problems including heart failure, myocardial infarction, unstable angina, congestive heart failure or cardiac arrythmia
  • Patient has a known sensitivity to the components of the study drug
  • Patient has not adequately recovered from any prior surgical procedure
  • Patient does not agree to refrain from use of herbal remedies and consumption of grapefruit juice for 2 weeks prior to and during the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00874731

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00874731     History of Changes
Other Study ID Numbers: 8669-037, 2009_569
Study First Received: March 31, 2009
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 16, 2014