Metastatic or Locally Advanced CancerPhase 1NCT00874731

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

A Phase 1 study testing Ridaforolimus 100 mg and Ridaforolimus 40 mg in people with Metastatic or Locally Advanced Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic or Locally Advanced Cancer
What is being tested?: Ridaforolimus 100 mg and Ridaforolimus 40 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 23 participants
Where: No sites listed yet
Study dates: 28 Apr 2009to 30 Apr 2010
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 17Show fewer

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.

About this study

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

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: Metastatic or Locally Advanced Cancer
Being tested: Ridaforolimus 100 mg, Ridaforolimus 40 mg, Placebo
Medical subject headings: Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ridaforolimus 100 mgDrug
Also called AP23573, MK-8669, deforolimus (until May 2009)
Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2.
Ridaforolimus 40 mgDrug
Also called AP23573, MK-8669, deforolimus (until May 2009)
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.
PlaceboDrug
Part 1: A single oral dose of placebo (10 x placebo tablets) was given on Day 1.

Study groups in NCT00874731
Study group	Role	What they receive
Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg	Experimental	[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. Receives: Drug: Ridaforolimus 100 mg; Drug: Ridaforolimus 40 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours
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.
Measured: Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour
The mean change from baseline (CFB) in QTcF at 1 hour post-dose was assessed. At baseline (pre-dose) and at 1 hour 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.
Measured: Baseline and 1 hour post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours
The mean change from baseline (CFB) in QTcF at 2 hours post-dose was assessed. At baseline (pre-dose) and at 2 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.
Measured: Baseline and 2 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours
The mean change from baseline (CFB) in QTcF at 3 hours post-dose was assessed. At baseline (pre-dose) and at 3 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.
Measured: Baseline and 3 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours
The mean change from baseline (CFB) in QTcF at 4 hours post-dose was assessed. At baseline (pre-dose) and at 4 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.
Measured: Baseline and 4 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours
The mean change from baseline (CFB) in QTcF at 6 hours post-dose was assessed. At baseline (pre-dose) and at 6 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.
Measured: Baseline and 6 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours
The mean change from baseline (CFB) in QTcF at 8 hours post-dose was assessed. At baseline (pre-dose) and at 8 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.
Measured: Baseline and 8 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours
The mean change from baseline (CFB) in QTcF at 10 hours post-dose was assessed. At baseline (pre-dose) and at 10 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.
Measured: Baseline and 10 hours post-dose on Days 1 & 2 of Part 1
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours
The mean change from baseline (CFB) in QTcF at 24 hours post-dose was assessed. At baseline (pre-dose) and at 24 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.
Measured: Baseline and 24 hours post-dose on Days 1 & 2 of Part 1

Secondary outcomes (2)

Number of Participants Experiencing an Adverse Event (AE)
The number of participants experiencing an AE was assessed. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Participants experiencing AEs were counted under the treatment they received when the AE occurred. Participants experiencing AEs during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm.
Measured: Up to 7 months
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
The number of participants discontinuing study treatment due to an AE was assessed. An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Participants discontinuing study treatment due to an AE were counted as discontinuing under the treatment they received when the AE occurred.
Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Apr 200930 Apr 2010

First posted2 Apr 2009 (estimated)
Study start28 Apr 2009
Primary completion30 Oct 2009
Study completion30 Apr 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Metastatic or Locally Advanced CancerStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: Single blind
Who is masked: Participant
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00874731
Sponsor's protocol ID: 8669-037
Other IDs: 2009_569, MK-8669-037
Status last verified: Apr 2019
First submitted: 31 Mar 2009
Last updated: 6 May 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Lush 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.
PubMed 22878520

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 6 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Clinical Trial to Assess the Effect of Ridaforolimus (AP23573; MK-8669) on QTc Interval in Patients
ClinicalTrials.gov ID: NCT00874731
Acronym / sponsor ID: 8669-037
Conditions: Metastatic or Locally Advanced Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 28 Apr 2009 (actual)
Primary completion: 30 Oct 2009 (actual)
Study completion: 30 Apr 2010 (actual)
First posted: 2 Apr 2009 (estimated)
Results: Posted 6 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: Single blind (participant)
Number of arms: 1

Arm	Type	Receives
Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg	Experimental	Drug: Ridaforolimus 100 mg, Drug: Ridaforolimus 40 mg, Drug: Placebo[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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ridaforolimus 100 mgAlso: AP23573, MK-8669, deforolimus (until May 2009)Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2.	Drug	Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg
Ridaforolimus 40 mgAlso: AP23573, MK-8669, deforolimus (until May 2009)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.	Drug	Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg
PlaceboPart 1: A single oral dose of placebo (10 x placebo tablets) was given on Day 1.	Drug	Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg

Primary outcome

Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours
Time frame: Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1
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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour
Time frame: Baseline and 1 hour post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 1 hour post-dose was assessed. At baseline (pre-dose) and at 1 hour 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours
Time frame: Baseline and 2 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 2 hours post-dose was assessed. At baseline (pre-dose) and at 2 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours
Time frame: Baseline and 3 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 3 hours post-dose was assessed. At baseline (pre-dose) and at 3 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours
Time frame: Baseline and 4 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 4 hours post-dose was assessed. At baseline (pre-dose) and at 4 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours
Time frame: Baseline and 6 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 6 hours post-dose was assessed. At baseline (pre-dose) and at 6 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours
Time frame: Baseline and 8 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 8 hours post-dose was assessed. At baseline (pre-dose) and at 8 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours
Time frame: Baseline and 10 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 10 hours post-dose was assessed. At baseline (pre-dose) and at 10 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours
Time frame: Baseline and 24 hours post-dose on Days 1 & 2 of Part 1
The mean change from baseline (CFB) in QTcF at 24 hours post-dose was assessed. At baseline (pre-dose) and at 24 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.

2 secondary outcomes

Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to 7 months
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
Time frame: Up to 6 months

Results and safety

Results posted to the registry on 6 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pt 1, Day 1. Placebo	23	22
Pt 1, Day 2. Ridaforolimus 100 mg	0	0
Pt 2. Ridaforolimus 40 mg	0	0

Primary outcome: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours

Time frame: Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1. Mean (95% Confidence Interval). Unit: milliseconds (msec)

Measure	Pt 1, Day 1. Placebo n = 22	Pt 1, Day 2. Ridaforolimus 100 mg n = 20
Baseline (Pre-dose)	419.23 (412.61 to 425.86)	418.08 (411.40 to 424.75)
Change from Baseline at 0.5 Hours	1.42 (-1.89 to 4.74)	1.90 (-1.53 to 5.33)

Pt 1, Day 1. Placebo vs Pt 1, Day 2. Ridaforolimus 100 mg: Mean Difference (Final Values): 0.48 (90% CI -2.80 to 3.76)

Population analysed: Includes only participants in Part 1 receiving treatment. QTcF not analyzed in Part 2. QTcF data are excluded from: 1) both arms (N=1; non-evaluable ECG waveform); and 2) ridaforolimus arm (N=2; protocol violation \& study discontinuation).

Primary outcome: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour

Time frame: Baseline and 1 hour post-dose on Days 1 & 2 of Part 1. Mean (95% Confidence Interval). Unit: msec

Measure	Pt 1, Day 1. Placebo n = 22	Pt 1, Day 2. Ridaforolimus 100 mg n = 20
Baseline (Pre-dose)	419.23 (412.61 to 425.86)	418.08 (411.40 to 424.75)
Change from Baseline at 1 Hour	2.40 (-0.92 to 5.71)	1.85 (-1.58 to 5.28)

Pt 1, Day 1. Placebo vs Pt 1, Day 2. Ridaforolimus 100 mg: Mean Difference (Final Values): -0.54 (95% CI -3.83 to 2.74)

Primary outcome: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours

Time frame: Baseline and 2 hours post-dose on Days 1 & 2 of Part 1. Mean (95% Confidence Interval). Unit: msec

Measure	Pt 1, Day 1. Placebo n = 22	Pt 1, Day 2. Ridaforolimus 100 mg n = 20
Baseline (Pre-dose)	419.23 (412.61 to 425.86)	418.08 (411.40 to 424.75)
Change from Baseline at 2 Hours	2.40 (-0.97 to 5.77)	1.22 (-2.21 to 4.65)

Pt 1, Day 1. Placebo vs Pt 1, Day 2. Ridaforolimus 100 mg: Mean Difference (Final Values): -1.18 (95% CI -4.50 to 2.14)

Primary outcome: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours

Time frame: Baseline and 3 hours post-dose on Days 1 & 2 of Part 1. Mean (95% Confidence Interval). Unit: msec

Measure	Pt 1, Day 1. Placebo n = 22	Pt 1, Day 2. Ridaforolimus 100 mg n = 20
Baseline (Pre-dose)	419.23 (412.61 to 425.86)	418.08 (411.40 to 424.75)
Change from Baseline at 3 Hours	2.94 (-0.42 to 6.31)	3.41 (-0.02 to 6.84)

Pt 1, Day 1. Placebo vs Pt 1, Day 2. Ridaforolimus 100 mg: Mean Difference (Final Values): 0.47 (95% CI -2.85 to 3.79)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 7 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pt 1, Day 1. Placebo	0 of 23 (0%)	8 of 23 (34.8%)	0 of 23
Pt 1, Day 2. Ridaforolimus 100 mg	0 of 22 (0%)	18 of 22 (81.8%)	0 of 22
Pt 2. Ridaforolimus 40 mg	8 of 22 (36.4%)	21 of 22 (95.5%)	2 of 22

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22878520Lush 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ridaforolimus 100 mg and Ridaforolimus 40 mg in people with Metastatic or Locally Advanced Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours (time frame: Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00874731, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2019.