Trial Outcomes & Findings for A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037) (NCT NCT00874731)

Last Updated: 2019-05-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1

Results posted on

2019-05-06

Participant Flow

A total of N=23 participants were enrolled in this study, conducted in 2 parts. Participants completing study Part 1 (Pt 1) had the option to continue to Part 2 (Pt 2).

Participants progressed through the study as a single group over 4 periods: 1) Pt 1, Day 1: Placebo; 2) Pt 1, Day 2: Ridaforolimus 100 mg; 3) washout period (≥5 days); and 4) Part 2: Ridaforolimus 40 mg.

Participant milestones

Participant milestones
Measure	Pt 1, Day 1. 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. Ridaforolimus 100 mg \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1, Day 1: Placebo STARTED	23	0	0
Part 1, Day 1: Placebo COMPLETED	22	0	0
Part 1, Day 1: Placebo NOT COMPLETED	1	0	0
Part 1, Day 2: Ridaforolimus 100 mg STARTED	0	22	0
Part 1, Day 2: Ridaforolimus 100 mg COMPLETED	0	22	0
Part 1, Day 2: Ridaforolimus 100 mg NOT COMPLETED	0	0	0
Washout Period STARTED	0	22	0
Washout Period COMPLETED	0	22	0
Washout Period NOT COMPLETED	0	0	0
Part 2: Ridaforolimus 40 mg STARTED	0	0	22
Part 2: Ridaforolimus 40 mg COMPLETED	0	0	0
Part 2: Ridaforolimus 40 mg NOT COMPLETED	0	0	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Pt 1, Day 1. Placebo \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 2. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1, Day 1: Placebo Disease Progression	1	0
Part 2: Ridaforolimus 40 mg Adverse Event	0	3
Part 2: Ridaforolimus 40 mg Disease Progression	0	19

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pt 1, Day 1. Placebo n=23 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.
Age, Continuous	54.4 years STANDARD_DEVIATION 11.59 • n=99 Participants
Sex: Female, Male Female	15 Participants n=99 Participants
Sex: Female, Male Male	8 Participants n=99 Participants

PRIMARY outcome

Timeframe: Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1

Population: 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).

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours Baseline (Pre-dose)	419.23 milliseconds (msec) Interval 412.61 to 425.86	418.08 milliseconds (msec) Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours Change from Baseline at 0.5 Hours	1.42 milliseconds (msec) Interval -1.89 to 4.74	1.90 milliseconds (msec) Interval -1.53 to 5.33	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour Change from Baseline at 1 Hour	2.40 msec Interval -0.92 to 5.71	1.85 msec Interval -1.58 to 5.28	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours Change from Baseline at 2 Hours	2.40 msec Interval -0.97 to 5.77	1.22 msec Interval -2.21 to 4.65	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours Change from Baseline at 3 Hours	2.94 msec Interval -0.42 to 6.31	3.41 msec Interval -0.02 to 6.84	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours Change from Baseline at 4 Hours	1.32 msec Interval -1.99 to 4.64	2.51 msec Interval -0.92 to 5.94	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours Change from Baseline at 6 Hours	-3.37 msec Interval -6.68 to -0.06	-0.87 msec Interval -4.3 to 2.56	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours Baseline	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours Change from Baseline at 8 Hours	-5.27 msec Interval -8.58 to -1.96	-2.79 msec Interval -6.22 to 0.64	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours Change from Baseline at 10 Hours	-5.00 msec Interval -8.32 to -1.69	-1.12 msec Interval -4.55 to 2.31	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=22 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=20 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg \[Pt 2\]: 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.
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours Baseline (Pre-dose)	419.23 msec Interval 412.61 to 425.86	418.08 msec Interval 411.4 to 424.75	—
Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours Change from Baseline at 24 Hours	-0.74 msec Interval -4.17 to 2.69	-2.24 msec Interval -5.67 to 1.19	—

SECONDARY outcome

Timeframe: Up to 7 months

Population: All participants receiving ≥1 dose of study treatment. The washout period following Part 1 was the safety follow-up period for Part 1. For this reason, AEs that occurred during the washout period are appropriately included as Part 1 AEs. One participant discontinued after the Day 1 placebo dose and did not receive ridaforolimus 100 mg or 40 mg.

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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=23 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=22 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg n=22 Participants \[Pt 2\]: 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.
Number of Participants Experiencing an Adverse Event (AE)	11 Participants	18 Participants	21 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: All participants receiving ≥1 dose of study treatment. One participant discontinued from study after the Day 1 placebo dose and did not receive ridaforolimus 100 mg or 40 mg.

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.

Outcome measures

Outcome measures
Measure	Pt 1, Day 1. Placebo n=23 Participants \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=22 Participants \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg n=22 Participants \[Pt 2\]: 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.
Number of Participants Discontinuing Study Treatment Due to an Adverse Event	0 Participants	0 Participants	3 Participants

Adverse Events

Pt 1, Day 1. Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Pt 1, Day 2. Ridaforolimus 100 mg

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Pt 2. Ridaforolimus 40 mg

Serious events: 8 serious events

Other events: 21 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Pt 1, Day 1. Placebo n=23 participants at risk \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1.	Pt 1, Day 2. Ridaforolimus 100 mg n=22 participants at risk \[Pt 1, Day 2\]: 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. Ridaforolimus 40 mg n=22 participants at risk \[Pt 2\]: 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.
Gastrointestinal disorders Ileus	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 2 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Gastrointestinal disorders Nausea	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Gastrointestinal disorders Vomiting	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Hepatobiliary disorders Cholangitis	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Infections and infestations Bronchitis viral	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Infections and infestations Pneumonia	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Infections and infestations Vulval abscess	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Metabolism and nutrition disorders Dehydration	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 2 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	9.1% 2/22 • Number of events 3 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 1 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/23 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	0.00% 0/22 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.	4.5% 1/22 • Number of events 2 • Up to 7 months The analysis population included all participants receiving ≥1 dose of study treatment. Participants with adverse events (AEs) were counted under the treatment received when the AE occurred. AEs that occurred during the washout period between Part 1 and Part 2 are counted in the "Pt 1, Day 2. Ridaforolimus 100 mg" arm. The washout period following Part 1 was the safety follow-up period for Part 1 and AEs that occurred during the washout period are appropriately included as Part 1 AEs.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER