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| ID | Type | Description | Link |
|---|---|---|---|
| 2009_569 | Other Identifier | NIH | |
| MK-8669-037 | Other Identifier | Merck Protocol Number |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ridaforolimus 100 mg | Drug | Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Baseline and 2 hours post-dose on Days 1 & 2 of Part 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22878520 | Result | 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. |
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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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1, Day 1: Placebo |
|
| ||||||||||||||||||
| Part 1, Day 2: Ridaforolimus 100 mg |
| |||||||||||||||||||
| Washout Period |
| |||||||||||||||||||
| Part 2: Ridaforolimus 40 mg |
|
Baseline data are reported for all participants starting the study on Day 1 of Part 1, receiving placebo treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | milliseconds (msec) | Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ileus | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 11.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C515074 | ridaforolimus |
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Participants will be blinded to treatment during Part 1 only.
|
| Ridaforolimus 40 mg | Drug | 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. |
|
|
| Placebo | Drug | Part 1: A single oral dose of placebo (10 x placebo tablets) was given on Day 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. | 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. | 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. | 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. | 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. | 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. | Baseline and 24 hours post-dose on Days 1 & 2 of Part 1 |
| 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. | Up to 6 months |
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 |
| 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. |
| OG001 | 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. |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Up to 7 months |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Up to 6 months |
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 1 hour post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 2 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 3 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 4 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 6 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 8 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 10 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 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. | 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). | Posted | Mean | 95% Confidence Interval | msec | Baseline and 24 hours post-dose on Days 1 & 2 of Part 1 |
|
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 8 |
| 23 |
| EG001 | 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. | 0 | 22 | 0 | 22 | 18 | 22 |
| EG002 | 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. | 2 | 22 | 8 | 22 | 21 | 22 |
| Nausea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 11.0 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 11.0 | Systematic Assessment |
|
| Bronchitis viral | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Vulval abscess | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
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| Oedema | General disorders | MedDRA 11.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 11.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 11.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
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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.
| Change from Baseline at 2 Hours |
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| Change from Baseline at 3 Hours |
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| Change from Baseline at 24 Hours |
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