Metastatic or Locally Advanced Cancer
Conditions
Brief summary
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).
Interventions
DRUGRidaforolimus 100 mg
Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2.
DRUGRidaforolimus 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.
DRUGPlacebo
Part 1: A single oral dose of placebo (10 x placebo tablets) was given on Day 1.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants will be blinded to treatment during Part 1 only.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours | 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. |
| Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours | 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 | 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 0.5 Hours | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Discontinuing Study Treatment Due to an Adverse Event | Up to 6 months | 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. |
| Number of Participants Experiencing an Adverse Event (AE) | Up to 7 months | 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. |
Participant flow
Recruitment details
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).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1, Day 1: Placebo | Disease Progression | 1 | 0 | 0 |
| Part 2: Ridaforolimus 40 mg | Adverse Event | 0 | 0 | 3 |
| Part 2: Ridaforolimus 40 mg | Disease Progression | 0 | 0 | 19 |
Baseline characteristics
| Characteristic | Pt 1, Day 1. Placebo |
|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 11.59 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 22 | 2 / 22 |
| other Total, other adverse events | 8 / 23 | 18 / 22 | 21 / 22 |
| serious Total, serious adverse events | 0 / 23 | 0 / 22 | 8 / 22 |
Outcome results
Primary
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.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | 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) |
| Pt 1, Day 1. Placebo | 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) |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours | Baseline (Pre-dose) | 418.08 milliseconds (msec) |
| Pt 1, Day 2. Ridaforolimus 100 mg | 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 | 1.90 milliseconds (msec) |
90% CI: [-2.8, 3.76]
Primary
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.
Time frame: Baseline and 10 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours | Change from Baseline at 10 Hours | -1.12 msec |
95% CI: [0.6, 7.17]
Primary
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.
Time frame: Baseline and 1 hour 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour | Change from Baseline at 1 Hour | 1.85 msec |
95% CI: [-3.83, 2.74]
Primary
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.
Time frame: Baseline and 24 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). Further, CFB data are excluded from the placebo arm for missing data (N=1) and study discontinuation (N=1).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours | Change from Baseline at 24 Hours | -2.24 msec |
95% CI: [-4.85, 1.86]
Primary
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.
Time frame: Baseline and 2 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). Further, CFB data are excluded from the placebo arm for missing data (N=1).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours | Change from Baseline at 2 Hours | 1.22 msec |
95% CI: [-4.5, 2.14]
Primary
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.
Time frame: Baseline and 3 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). Further, CFB data are excluded from the placebo arm for missing data (N=1).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours | Change from Baseline at 3 Hours | 3.41 msec |
95% CI: [-2.85, 3.79]
Primary
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.
Time frame: Baseline and 4 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours | Change from Baseline at 4 Hours | 2.51 msec |
95% CI: [-2.1, 4.47]
Primary
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.
Time frame: Baseline and 6 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours | Baseline (Pre-dose) | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours | Baseline (Pre-dose) | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours | Change from Baseline at 6 Hours | -0.87 msec |
95% CI: [-0.79, 5.78]
Primary
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.
Time frame: Baseline and 8 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pt 1, Day 1. Placebo | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours | Baseline | 419.23 msec |
| Pt 1, Day 1. Placebo | 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 |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours | Baseline | 418.08 msec |
| Pt 1, Day 2. Ridaforolimus 100 mg | Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours | Change from Baseline at 8 Hours | -2.79 msec |
95% CI: [-0.8, 5.76]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pt 1, Day 1. Placebo | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 0 Participants |
| Pt 1, Day 2. Ridaforolimus 100 mg | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 0 Participants |
| Pt 2. Ridaforolimus 40 mg | Number of Participants Discontinuing Study Treatment Due to an Adverse Event | 3 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pt 1, Day 1. Placebo | Number of Participants Experiencing an Adverse Event (AE) | 11 Participants |
| Pt 1, Day 2. Ridaforolimus 100 mg | Number of Participants Experiencing an Adverse Event (AE) | 18 Participants |
| Pt 2. Ridaforolimus 40 mg | Number of Participants Experiencing an Adverse Event (AE) | 21 Participants |