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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1156-4099 | Other Identifier | World Health Organization |
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The purpose of this study is to characterize the effect of a single dose of 40 mg sapanisertib (MLN0128) on the electrocardiographic QT/QTc interval in participants with advanced solid tumors.
The drug being tested in this study is called sapanisertib (MLN0128). Sapanisertib is being tested to determine the effect of a single 40 mg dose on the electrocardiographic measure of the time between the start of the Q wave and the end of the T wave in the electrical cycle of the heart (QT)/rate corrected QT (QTc) interval in patients with advanced solid tumors. This study will look at electrocardiogram (ECG) results before and after a single dose of sapanisertib.
The study will enroll approximately 30 patients. All participants will receive a single 40 mg dose of sapanisertib capsules on Day 1. Participants may continue to receive sapanisertib for up to 1 year at a dose of up to 30 mg once weekly if a clinical benefit is being derived.
This multi-centre trial will be conducted in the United States. The overall time to participate in this study is up to 14 months. Participants will make 6 visits to the clinic and end of study visit 30 to 40 days after last dose of study drug for a follow-up assessment. Participants that continue treatment with sapanisertib will continue to make additional visits to the clinic once or twice every 4 weeks and the end of study visit 30 to 40 days after last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sapanisertib | Experimental | Sapanisertib starting dose of 40 mg, capsules, orally, once, on Day 1, Cycle 1 (28 days cycle) followed by sapanisertib 30 mg, capsules, orally, once weekly (QW) starting on Cycle 1, Day 8 based on safety and tolerability and as per investigator's discretion up to disease progression, unacceptable sapanisertib-related toxicity, withdrawal of consent, or for up to 12 months (whichever occurred first). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sapanisertib | Drug | Sapanisertib capsules. |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval | The mean changes of QTcI from time-matched baseline was measured by electrocardiogram (ECG) to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcI interval. | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarasota | Florida | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32488989 | Derived | Patel C, Goel S, Patel MR, Rangachari L, Wilbur JD, Shou Y, Venkatakrishnan K, Lockhart AC. Phase 1 Study to Evaluate the Effect of the Investigational Anticancer Agent Sapanisertib on the QTc Interval in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2020 Oct;9(7):876-888. doi: 10.1002/cpdd.808. Epub 2020 Jun 2. |
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Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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Participants who had advanced solid tumors were enrolled to receive sapanisertib 40 mg on Day 1. Participants then received sapanisertib 30 mg once weekly (QW) until they experienced disease progression or unacceptable sapanisertib-related toxicity or withdrawal of consent or for up to 12 months (whichever occurred first).
Participants took part in the study at 5 investigative sites in the United States from 15 Sep 2014 to 28 Feb 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sapanisertib | Sapanisertib starting dose of 40 mg, capsules, orally, once, on Day 1, Cycle 1 (28 days cycle) followed by sapanisertib 30 mg, capsules, orally, once weekly (QW) starting on Cycle 1, Day 8 based on safety and tolerability and as per investigator's discretion up to disease progression, unacceptable sapanisertib-related toxicity, withdrawal of consent, or for up to 12 months (whichever occurred first). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population included all participants who received at least 1 dose of Sapanisertib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sapanisertib | Sapanisertib starting dose of 40 mg, capsules, orally, once, on Day 1, Cycle 1 followed by sapanisertib 30 mg, capsules, orally, once weekly (QW) starting on Cycle 1, Day 8 based on safety and tolerability and as per investigator's discretion up to disease progression, unacceptable sapanisertib-related toxicity, withdrawal of consent, or for up to 12 months (whichever occurred first). |
| 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 | Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval | The mean changes of QTcI from time-matched baseline was measured by electrocardiogram (ECG) to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcI interval. | Primary analysis population: participants that have all timepoints collected on Holter ECG monitoring on Day -1 and Day 1 of Cycle 1 including ECG timepoints on Cycle 1 Days 1 to 3 at 24 or 48 hours postdose and baseline comparisons available for these analyses. Number analyzed is number of participants with evaluable data at given time-point. | Posted | Mean | Standard Deviation | msec | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
|
From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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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 | Sapanisertib | Sapanisertib starting dose of 40 mg, capsules, orally, once, on Day 1, Cycle 1 followed by sapanisertib 30 mg, capsules, orally, once weekly (QW) starting on Cycle 1, Day 8 based on safety and tolerability and as per investigator's discretion up to disease progression, unacceptable sapanisertib-related toxicity, withdrawal of consent, or for up to 12 months (whichever occurred first). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Small Intestinal Obstruction | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 28, 2017 | Feb 18, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 18, 2015 | Feb 18, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C572449 | sapanisertib |
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| From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months) |
| Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE | The laboratory parameters included clinical chemistry, hematology, and urinalysis. Any abnormal change in the laboratory values were assessed by Investigator and reported as AE. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. | From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months) |
| Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE | Vital sign measurements included blood pressure (diastolic and systolic), heart rate, and temperature. Any abnormal change in the vital sign values were assessed by Investigator and reported as AE. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. | From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months) |
| Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB) | The mean changes of QTcB from time-matched baseline was measured by ECG to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcB interval. | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
| Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF) | The mean changes of QTcF from time-matched baseline was measured by ECG to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcF interval. | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
| Change From Time-Matched Baseline in QRS Interval | QRS interval is defined as the time between the start of the Q wave and end of the S wave on ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QRS interval. | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
| Change From Time-Matched Baseline in PR Interval | PR interval is defined as the time between the start of the P wave and the beginning of the QRS complex on ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of PR interval. | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
| Change From Time-Matched Baseline in Heart Rate | Heart rate was assessed using the ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measure mixed effects linear model. A negative change from baseline indicates decrease in heart rate. | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
| Cmax: Maximum Observed Plasma Concentration for Sapanisertib | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
| Tmax: Time to Reach Cmax for Sapanisertib | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
| AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration for Sapanisertib | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
| AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Sapanisertib | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
| T1/2: Terminal Elimination Half-life for Sapanisertib | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
| St Louis |
| Missouri |
| United States |
| The Bronx | New York | United States |
| Oklahoma City | Oklahoma | United States |
| Dallas | Texas | United States |
| Reason Not Specified |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Number analyzed is the number of participants with evaluable data at Baseline. | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index (BMI) | BMI=weight(kg)/height(m)^2 | Number analyzed is the number of participants with evaluable data at Baseline. | Mean | Standard Deviation | kg/m^2 |
|
| Sapanisertib |
Sapanisertib starting dose of 40 mg, capsules, orally, once, on Day 1, Cycle 1 followed by sapanisertib 30 mg, capsules, orally, once weekly (QW) starting on Cycle 1, Day 8 based on safety and tolerability and as per investigator's discretion up to disease progression, unacceptable sapanisertib-related toxicity, withdrawal of consent, or for up to 12 months (whichever occurred first). |
|
|
|
| Secondary | Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. | Safety population included all participants who received at least 1 dose of sapanisertib. | Posted | Count of Participants | Participants | From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months) |
|
|
|
| Secondary | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE | The laboratory parameters included clinical chemistry, hematology, and urinalysis. Any abnormal change in the laboratory values were assessed by Investigator and reported as AE. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. | Safety population included all participants who received at least 1 dose of sapanisertib. | Posted | Count of Participants | Participants | From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months) |
|
|
|
| Secondary | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE | Vital sign measurements included blood pressure (diastolic and systolic), heart rate, and temperature. Any abnormal change in the vital sign values were assessed by Investigator and reported as AE. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. | Safety population included all participants who received at least 1 dose of sapanisertib. | Posted | Count of Participants | Participants | From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months) |
|
|
|
| Secondary | Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB) | The mean changes of QTcB from time-matched baseline was measured by ECG to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcB interval. | Primary analysis population: participants that have all timepoints collected on Holter ECG monitoring on Day -1 and Day 1 of Cycle 1 including ECG timepoints on Cycle 1 Days 1 to 3 at 24 or 48 hours postdose and baseline comparisons available for these analyses. Number analyzed is number of participants with evaluable data at given time-point. | Posted | Mean | Standard Deviation | msec | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
|
|
|
| Secondary | Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF) | The mean changes of QTcF from time-matched baseline was measured by ECG to evaluate the potential effect of drug on QTc interval duration. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QTcF interval. | Primary analysis population: participants that have all timepoints collected on Holter ECG monitoring on Day -1 and Day 1 of Cycle 1 including ECG timepoints on Cycle 1 Days 1 to 3 at 24 or 48 hours postdose and baseline comparisons available for these analyses. Number analyzed is number of participants with evaluable data at given time-point. | Posted | Mean | Standard Deviation | msec | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
|
|
|
| Secondary | Change From Time-Matched Baseline in QRS Interval | QRS interval is defined as the time between the start of the Q wave and end of the S wave on ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of QRS interval. | Primary analysis population: participants that have all timepoints collected on Holter ECG monitoring on Day -1 and Day 1 of Cycle 1 including ECG timepoints on Cycle 1 Days 1 to 3 at 24 or 48 hours postdose and baseline comparisons available for these analyses. Number analyzed is number of participants with evaluable data at given time-point. | Posted | Mean | Standard Deviation | msec | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
|
|
|
| Secondary | Change From Time-Matched Baseline in PR Interval | PR interval is defined as the time between the start of the P wave and the beginning of the QRS complex on ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measures mixed effects linear model. A negative change from baseline indicates shortening and a positive change from baseline indicates prolongation of PR interval. | Primary analysis population: participants that have all timepoints collected on Holter ECG monitoring on Day -1 and Day 1 of Cycle 1 including ECG timepoints on Cycle 1 Days 1 to 3 at 24 or 48 hours postdose and baseline comparisons available for these analyses. Number analyzed is number of participants with evaluable data at given time-point. | Posted | Mean | Standard Deviation | msec | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
|
|
|
| Secondary | Change From Time-Matched Baseline in Heart Rate | Heart rate was assessed using the ECG. Holter monitors were used to collect triplicate ECG measurements and were based on a repeated measure mixed effects linear model. A negative change from baseline indicates decrease in heart rate. | Primary analysis population: participants that have all timepoints collected on Holter ECG monitoring on Day -1 and Day 1 of Cycle 1 including ECG timepoints on Cycle 1 Days 1 to 3 at 24 or 48 hours postdose and baseline comparisons available for these analyses. Number analyzed is number of participants with evaluable data at given time-point. | Posted | Mean | Standard Deviation | beats per minute (bpm) | Baseline; Cycle 1 (28 days cycle): 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24 and 48 hours postdose |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration for Sapanisertib | Pharmacokinetic (PK) analysis population included all participants who received at least 1 dose of sapanisertib and had sufficient concentration-time data to calculate 1 or more PK parameters. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
|
|
|
| Secondary | Tmax: Time to Reach Cmax for Sapanisertib | PK analysis population included all participants who received at least 1 dose of sapanisertib and had sufficient concentration-time data to calculate 1 or more PK parameters. | Posted | Median | Full Range | hours | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
|
|
|
| Secondary | AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration for Sapanisertib | PK analysis population included all participants who received at least 1 dose of sapanisertib and had sufficient concentration-time data to calculate 1 or more PK parameters. Overall number of participants analyzed were participants with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | h*ng/mL | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
|
|
|
| Secondary | AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Sapanisertib | PK analysis population included all participants who received at least 1 dose of sapanisertib and had sufficient concentration-time data to calculate 1 or more PK parameters. Overall number of participants analyzed were participants with data available for analysis of this outcome measure. | Posted | Mean | Standard Deviation | h*ng/mL | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
|
|
|
| Secondary | T1/2: Terminal Elimination Half-life for Sapanisertib | PK analysis population included all participants who received at least 1 dose of sapanisertib and had sufficient concentration-time data to calculate 1 or more PK parameters. Overall number of participants analyzed were participants with data available for analysis of this outcome measure. | Posted | Median | Full Range | hours | Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdose |
|
|
|
| 2 |
| 44 |
| 18 |
| 44 |
| 43 |
| 44 |
| Small Intestinal Perforation | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with sapanisertib and is not related. |
|
| Stomatitis | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Non-Cardiac Chest Pain | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Bile Duct Obstruction | Hepatobiliary disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA version 19.0 | Systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA version 19.0 | Systematic Assessment |
|
| Post Procedural Fever | Injury, poisoning and procedural complications | MedDRA version 19.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Flank Pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Breast Cancer Metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with sapanisertib and is not related. |
|
| Mental Status Changes | Psychiatric disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Sinus Tachycardia | Cardiac disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Vision Blurred | Eye disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Gait Disturbance | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA version 19.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA version 19.0 | Systematic Assessment |
|
| Weight Decreased | Investigations | MedDRA version 19.0 | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Systematic Assessment |
|
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 19.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 19.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA version 19.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA version 19.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA version 19.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA version 19.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA version 19.0 | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA version 19.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
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| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 19.0 | Systematic Assessment |
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| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA version 19.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 19.0 | Systematic Assessment |
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In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| Title | Measurements |
|---|---|
|
| Hypertriglyceridemia |
|
| Hypomagnesemia |
|
| Hypophosphatemia |
|
| Vitamin D Deficiency |
|
| Anemia |
|
| Thrombocytopenia |
|
| Title | Measurements |
|---|---|
|
|
| Change from Baseline at 1 Hour Postdose |
|
|
| Change from Baseline at 1.5 Hours Postdose |
|
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| Change from Baseline at 2 Hours Postdose |
|
|
| Change from Baseline at 2.5 Hours Postdose |
|
|
| Change from Baseline at 3 Hours Postdose |
|
|
| Change from Baseline at 4 Hours Postdose |
|
|
| Change from Baseline at 6 Hours Postdose |
|
|
| Change from Baseline at 8 Hours Postdosen |
|
|
| Change from Baseline at 10 Hours Postdose |
|
|
| Change from Baseline at 24 Hours Postdose |
|
|
| Change from Baseline at 48 Hours Postdose |
|
|
|
| Change from Baseline at 1 Hour Postdose |
|
|
| Change from Baseline at 1.5 Hours Postdose |
|
|
| Change from Baseline at 2 Hours Postdose |
|
|
| Change from Baseline at 2.5 Hours Postdose |
|
|
| Change from Baseline at 3 Hours Postdose |
|
|
| Change from Baseline at 4 Hours Postdose |
|
|
| Change from Baseline at 6 Hours Postdose |
|
|
| Change from Baseline at 8 Hours Postdose |
|
|
| Change from Baseline at 10 Hours Postdose |
|
|
| Change from Baseline at 24 Hours Postdose |
|
|
| Change from Baseline at 48 Hours Postdose |
|
|
|
| Change from Baseline at 1 Hour Postdose |
|
|
| Change from Baseline at 1.5 Hours Postdose |
|
|
| Change from Baseline at 2 Hours Postdose |
|
|
| Change from Baseline at 2.5 Hours Postdose |
|
|
| Change from Baseline at 3 Hours Postdose |
|
|
| Change from Baseline at 4 Hours Postdose |
|
|
| Change from Baseline at 6 Hours Postdose |
|
|
| Change from Baseline at 8 Hours Postdosen |
|
|
| Change from Baseline at 10 Hours Postdose |
|
|
| Change from Baseline at 24 Hours Postdose |
|
|
| Change from Baseline at 48 Hours Postdose |
|
|
|
| Change from Baseline at 1 Hour Postdose |
|
|
| Change from Baseline at 1.5 Hours Postdose |
|
|
| Change from Baseline at 2 Hours Postdose |
|
|
| Change from Baseline at 2.5 Hours Postdose |
|
|
| Change from Baseline at 3 Hours Postdose |
|
|
| Change from Baseline at 4 Hours Postdose |
|
|
| Change from Baseline at 6 Hours Postdose |
|
|
| Change from Baseline at 8 Hours Postdosen |
|
|
| Change from Baseline at 10 Hours Postdose |
|
|
| Change from Baseline at 24 Hours Postdose |
|
|
| Change from Baseline at 48 Hours Postdose |
|
|
|
| Change from Baseline at 1 Hour Postdose |
|
|
| Change from Baseline at 1.5 Hours Postdose |
|
|
| Change from Baseline at 2 Hours Postdose |
|
|
| Change from Baseline at 2.5 Hours Postdose |
|
|
| Change from Baseline at 3 Hours Postdose |
|
|
| Change from Baseline at 4 Hours Postdose |
|
|
| Change from Baseline at 6 Hours Postdose |
|
|
| Change from Baseline at 8 Hours Postdose |
|
|
| Change from Baseline at 10 Hours Postdose |
|
|
| Change from Baseline at 24 Hours Postdose |
|
|
| Change from Baseline at 48 Hours Postdose |
|
|