Trial Outcomes & Findings for Effect of Sapanisertib (MLN0128) on the QTc Interval in Participants With Advanced Solid Tumors (NCT NCT02197572)
NCT ID: NCT02197572
Last Updated: 2023-01-23
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
44 participants
Primary outcome timeframe
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
Results posted on
2023-01-23
Participant Flow
Participants took part in the study at 5 investigative sites in the United States from 15 Sep 2014 to 28 Feb 2019.
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).
Participant milestones
| Measure |
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).
|
|---|---|
|
Overall Study
STARTED
|
44
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
44
|
Reasons for withdrawal
| Measure |
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).
|
|---|---|
|
Overall Study
Progressive Disease
|
28
|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Reason Not Specified
|
4
|
Baseline Characteristics
Number analyzed is the number of participants with evaluable data at Baseline.
Baseline characteristics by cohort
| Measure |
Sapanisertib
n=44 Participants
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).
|
|---|---|
|
Age, Continuous
|
58.6 years
STANDARD_DEVIATION 12.24 • n=44 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=44 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=44 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=44 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=44 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=44 Participants
|
|
Height
|
166.8 cm
STANDARD_DEVIATION 8.61 • n=42 Participants • Number analyzed is the number of participants with evaluable data at Baseline.
|
|
Weight
|
74.9 kg
STANDARD_DEVIATION 16.08 • n=44 Participants
|
|
Body Mass Index (BMI)
|
27.141 kg/m^2
STANDARD_DEVIATION 5.8591 • n=42 Participants • Number analyzed is the number of participants with evaluable data at Baseline.
|
PRIMARY outcome
Timeframe: 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 postdosePopulation: 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.
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.
Outcome measures
| Measure |
Sapanisertib
n=32 Participants
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).
|
|---|---|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 0.25 Hours Postdose
|
-1.3 msec
Standard Deviation 9.5
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 0.5 Hours Postdose
|
-7.7 msec
Standard Deviation 9.8
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 1 Hour Postdose
|
-1.1 msec
Standard Deviation 11.5
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 1.5 Hours Postdose
|
-2.0 msec
Standard Deviation 12.5
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 2 Hours Postdose
|
-4.2 msec
Standard Deviation 11.2
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 2.5 Hours Postdose
|
-6.9 msec
Standard Deviation 10.6
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 3 Hours Postdose
|
-8.5 msec
Standard Deviation 11.2
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 4 Hours Postdose
|
-6.6 msec
Standard Deviation 9.3
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 6 Hours Postdose
|
-8.8 msec
Standard Deviation 15.6
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 8 Hours Postdose
|
-1.3 msec
Standard Deviation 14.1
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 10 Hours Postdose
|
-5.6 msec
Standard Deviation 17.5
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 24 Hours Postdose
|
7.1 msec
Standard Deviation 25.4
|
|
Mean Change From Time-Matched Baseline in QTcI, Individual Baseline Corrected Rate-Corrected QT Interval
Change from Baseline at 48 Hours Postdose
|
3.1 msec
Standard Deviation 17.8
|
SECONDARY outcome
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)Population: Safety population included all participants who received at least 1 dose of sapanisertib.
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.
Outcome measures
| Measure |
Sapanisertib
n=44 Participants
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).
|
|---|---|
|
Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE)
AE
|
43 Participants
|
|
Number of Participants With Atleast One Adverse Event (AE) and Serious Adverse Event (SAE)
SAE
|
18 Participants
|
SECONDARY outcome
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)Population: Safety population included all participants who received at least 1 dose of sapanisertib.
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.
Outcome measures
| Measure |
Sapanisertib
n=44 Participants
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).
|
|---|---|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Blood Creatinine Increased
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Hypomagnesemia
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Hypophosphatemia
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Blood Triglycerides Increased
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Hyperglycemia
|
8 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Hypertriglyceridemia
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Vitamin D Deficiency
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Anemia
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Reported as AE
Thrombocytopenia
|
1 Participants
|
SECONDARY outcome
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (Up to 13 months)Population: Safety population included all participants who received at least 1 dose of sapanisertib.
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.
Outcome measures
| Measure |
Sapanisertib
n=44 Participants
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).
|
|---|---|
|
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE
Hypotension
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE
Postoperative Fever
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Reported as AE
Pyrexia
|
4 Participants
|
SECONDARY outcome
Timeframe: 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 postdosePopulation: 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.
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.
Outcome measures
| Measure |
Sapanisertib
n=32 Participants
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).
|
|---|---|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 0.25 Hours Postdose
|
-1.9 msec
Standard Deviation 9.7
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 0.5 Hours Postdose
|
-9.8 msec
Standard Deviation 12.1
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 1 Hour Postdose
|
-2.0 msec
Standard Deviation 12.4
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 1.5 Hours Postdose
|
-3.1 msec
Standard Deviation 13.5
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 2 Hours Postdose
|
-5.1 msec
Standard Deviation 11.4
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 2.5 Hours Postdose
|
-7.5 msec
Standard Deviation 10.6
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 3 Hours Postdose
|
-8.3 msec
Standard Deviation 14.6
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 4 Hours Postdose
|
-8.5 msec
Standard Deviation 8.7
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 6 Hours Postdose
|
-5.9 msec
Standard Deviation 12.2
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 8 Hours Postdosen
|
1.9 msec
Standard Deviation 13.7
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 10 Hours Postdose
|
-4.4 msec
Standard Deviation 15.3
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 24 Hours Postdose
|
11.9 msec
Standard Deviation 17.0
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval With Bazett Correction (QTcB)
Change from Baseline at 48 Hours Postdose
|
7.6 msec
Standard Deviation 14.9
|
SECONDARY outcome
Timeframe: 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 postdosePopulation: 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.
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.
Outcome measures
| Measure |
Sapanisertib
n=32 Participants
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).
|
|---|---|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 0.25 Hours Postdose
|
-1.3 msec
Standard Deviation 8.5
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 0.5 Hours Postdose
|
-5.0 msec
Standard Deviation 10.6
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 1 Hour Postdose
|
2.1 msec
Standard Deviation 12.0
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 1.5 Hours Postdose
|
0.6 msec
Standard Deviation 12.7
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 2 Hours Postdose
|
-3.3 msec
Standard Deviation 12.2
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 2.5 Hours Postdose
|
-7.0 msec
Standard Deviation 11.1
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 3 Hours Postdose
|
-7.4 msec
Standard Deviation 13.2
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 4 Hours Postdose
|
-7.7 msec
Standard Deviation 10.3
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 6 Hours Postdose
|
-10.1 msec
Standard Deviation 13.0
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 8 Hours Postdose
|
-4.0 msec
Standard Deviation 15.1
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 10 Hours Postdose
|
-11.9 msec
Standard Deviation 16.1
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 24 Hours Postdose
|
0.8 msec
Standard Deviation 16.0
|
|
Mean Change From Time-Matched Baseline in QTc With Rate-Corrected QT Interval Fridericia Correction (QTcF)
Change from Baseline at 48 Hours Postdose
|
2.5 msec
Standard Deviation 13.2
|
SECONDARY outcome
Timeframe: 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 postdosePopulation: 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.
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.
Outcome measures
| Measure |
Sapanisertib
n=32 Participants
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).
|
|---|---|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 0.25 Hours Postdose
|
-0.7 msec
Standard Deviation 3.3
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 0.5 Hours Postdose
|
-1.4 msec
Standard Deviation 3.3
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 1 Hour Postdose
|
-2.8 msec
Standard Deviation 2.9
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 1.5 Hours Postdose
|
-1.8 msec
Standard Deviation 4.1
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 2 Hours Postdose
|
-1.4 msec
Standard Deviation 4.0
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 2.5 Hours Postdose
|
-2.3 msec
Standard Deviation 4.7
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 3 Hours Postdose
|
-2.4 msec
Standard Deviation 3.2
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 4 Hours Postdose
|
-2.9 msec
Standard Deviation 3.2
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 6 Hours Postdose
|
-1.3 msec
Standard Deviation 3.0
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 8 Hours Postdosen
|
-0.8 msec
Standard Deviation 4.1
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 10 Hours Postdose
|
-4.0 msec
Standard Deviation 6.5
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 24 Hours Postdose
|
-1.4 msec
Standard Deviation 4.0
|
|
Change From Time-Matched Baseline in QRS Interval
Change from Baseline at 48 Hours Postdose
|
0.2 msec
Standard Deviation 5.3
|
SECONDARY outcome
Timeframe: 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 postdosePopulation: 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.
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.
Outcome measures
| Measure |
Sapanisertib
n=32 Participants
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).
|
|---|---|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 0.25 Hours Postdose
|
-1.8 msec
Standard Deviation 13.9
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 0.5 Hours Postdose
|
-0.8 msec
Standard Deviation 13.6
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 1 Hour Postdose
|
0.7 msec
Standard Deviation 11.5
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 1.5 Hours Postdose
|
-0.7 msec
Standard Deviation 11.4
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 2 Hours Postdose
|
-1.7 msec
Standard Deviation 9.3
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 2.5 Hours Postdose
|
0.1 msec
Standard Deviation 11.7
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 3 Hours Postdose
|
-2.7 msec
Standard Deviation 10.8
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 4 Hours Postdose
|
-1.9 msec
Standard Deviation 13.3
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 6 Hours Postdose
|
-8.9 msec
Standard Deviation 13.2
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 8 Hours Postdosen
|
-7.3 msec
Standard Deviation 11.4
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 10 Hours Postdose
|
-12.3 msec
Standard Deviation 11.5
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 24 Hours Postdose
|
-6.8 msec
Standard Deviation 15.7
|
|
Change From Time-Matched Baseline in PR Interval
Change from Baseline at 48 Hours Postdose
|
-2.9 msec
Standard Deviation 20.7
|
SECONDARY outcome
Timeframe: 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 postdosePopulation: 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.
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.
Outcome measures
| Measure |
Sapanisertib
n=32 Participants
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).
|
|---|---|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 0.25 Hours Postdose
|
-0.9 beats per minute (bpm)
Standard Deviation 5.7
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 0.5 Hours Postdose
|
-4.7 beats per minute (bpm)
Standard Deviation 5.9
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 1 Hour Postdose
|
-4.2 beats per minute (bpm)
Standard Deviation 6.6
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 1.5 Hours Postdose
|
-3.7 beats per minute (bpm)
Standard Deviation 6.0
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 2 Hours Postdose
|
-1.0 beats per minute (bpm)
Standard Deviation 8.2
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 2.5 Hours Postdose
|
-0.3 beats per minute (bpm)
Standard Deviation 4.8
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 3 Hours Postdose
|
-0.3 beats per minute (bpm)
Standard Deviation 7.2
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 4 Hours Postdose
|
-0.4 beats per minute (bpm)
Standard Deviation 10.1
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 6 Hours Postdose
|
4.8 beats per minute (bpm)
Standard Deviation 6.3
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 8 Hours Postdose
|
7.0 beats per minute (bpm)
Standard Deviation 9.7
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 10 Hours Postdose
|
7.9 beats per minute (bpm)
Standard Deviation 9.2
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 24 Hours Postdose
|
12.4 beats per minute (bpm)
Standard Deviation 11.8
|
|
Change From Time-Matched Baseline in Heart Rate
Change from Baseline at 48 Hours Postdose
|
5.0 beats per minute (bpm)
Standard Deviation 9.8
|
SECONDARY outcome
Timeframe: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdosePopulation: 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.
Outcome measures
| Measure |
Sapanisertib
n=44 Participants
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).
|
|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Sapanisertib
|
337.1 ng/mL
Standard Deviation 178.27
|
SECONDARY outcome
Timeframe: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdosePopulation: 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.
Outcome measures
| Measure |
Sapanisertib
n=44 Participants
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).
|
|---|---|
|
Tmax: Time to Reach Cmax for Sapanisertib
|
1.5167 hours
Interval 0.5 to 24.0
|
SECONDARY outcome
Timeframe: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdosePopulation: 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.
Outcome measures
| Measure |
Sapanisertib
n=37 Participants
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).
|
|---|---|
|
AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Measurable Concentration for Sapanisertib
|
2875.7406 h*ng/mL
Standard Deviation 2110.90918
|
SECONDARY outcome
Timeframe: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdosePopulation: 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.
Outcome measures
| Measure |
Sapanisertib
n=36 Participants
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).
|
|---|---|
|
AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Sapanisertib
|
2992.5394 h*ng/mL
Standard Deviation 2405.41705
|
SECONDARY outcome
Timeframe: Cycle 1 (28 days cycle), Day 1, predose and at multiple timepoints (Up to 48 hours) postdosePopulation: 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.
Outcome measures
| Measure |
Sapanisertib
n=36 Participants
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).
|
|---|---|
|
T1/2: Terminal Elimination Half-life for Sapanisertib
|
9.0682 hours
Interval 4.477 to 16.867
|
Adverse Events
Sapanisertib
Serious events: 18 serious events
Other events: 43 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Sapanisertib
n=44 participants at risk
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).
|
|---|---|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
2.3%
1/44 • 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.
|
|
Gastrointestinal disorders
Small Intestinal Perforation
|
2.3%
1/44 • 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.
|
|
Gastrointestinal disorders
Stomatitis
|
2.3%
1/44 • 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.
|
|
General disorders
Fatigue
|
2.3%
1/44 • 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.
|
|
General disorders
Non-Cardiac Chest Pain
|
2.3%
1/44 • 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.
|
|
Hepatobiliary disorders
Bile Duct Obstruction
|
2.3%
1/44 • 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.
|
|
Immune system disorders
Hypersensitivity
|
2.3%
1/44 • 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.
|
|
Infections and infestations
Appendicitis
|
2.3%
1/44 • 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.
|
|
Infections and infestations
Pyelonephritis
|
2.3%
1/44 • 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.
|
|
Injury, poisoning and procedural complications
Post Procedural Fever
|
2.3%
1/44 • 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.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.3%
1/44 • 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.
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
4.5%
2/44 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.3%
1/44 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer Metastatic
|
2.3%
1/44 • 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.
|
|
Psychiatric disorders
Mental Status Changes
|
2.3%
1/44 • 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.
|
|
Renal and urinary disorders
Haematuria
|
2.3%
1/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.3%
1/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
2.3%
1/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
2.3%
1/44 • 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.
|
|
Vascular disorders
Deep Vein Thrombosis
|
2.3%
1/44 • 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.
|
Other adverse events
| Measure |
Sapanisertib
n=44 participants at risk
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).
|
|---|---|
|
Injury, poisoning and procedural complications
Fall
|
9.1%
4/44 • 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.
|
|
Investigations
Weight Decreased
|
31.8%
14/44 • 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.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
50.0%
22/44 • 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.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
18.2%
8/44 • 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.
|
|
Metabolism and nutrition disorders
Dehydration
|
13.6%
6/44 • 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.
|
|
Blood and lymphatic system disorders
Anaemia
|
6.8%
3/44 • 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.
|
|
Cardiac disorders
Sinus Tachycardia
|
9.1%
4/44 • 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.
|
|
Eye disorders
Vision Blurred
|
11.4%
5/44 • 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.
|
|
Gastrointestinal disorders
Nausea
|
79.5%
35/44 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
56.8%
25/44 • 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.
|
|
Gastrointestinal disorders
Diarrhoea
|
34.1%
15/44 • 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.
|
|
Gastrointestinal disorders
Stomatitis
|
22.7%
10/44 • 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.
|
|
Gastrointestinal disorders
Constipation
|
20.5%
9/44 • 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.
|
|
Gastrointestinal disorders
Dry Mouth
|
11.4%
5/44 • 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.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.4%
5/44 • 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.
|
|
Gastrointestinal disorders
Abdominal Pain
|
9.1%
4/44 • 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.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.1%
4/44 • 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.
|
|
General disorders
Fatigue
|
63.6%
28/44 • 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.
|
|
General disorders
Chills
|
9.1%
4/44 • 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.
|
|
General disorders
Gait Disturbance
|
9.1%
4/44 • 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.
|
|
General disorders
Pyrexia
|
9.1%
4/44 • 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.
|
|
General disorders
Oedema Peripheral
|
6.8%
3/44 • 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.
|
|
Infections and infestations
Urinary Tract Infection
|
29.5%
13/44 • 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.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
20.5%
9/44 • 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.
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
11.4%
5/44 • 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.
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
9.1%
4/44 • 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.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.8%
3/44 • 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.
|
|
Nervous system disorders
Dizziness
|
20.5%
9/44 • 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.
|
|
Nervous system disorders
Headache
|
18.2%
8/44 • 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.
|
|
Nervous system disorders
Dysgeusia
|
11.4%
5/44 • 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.
|
|
Nervous system disorders
Tremor
|
6.8%
3/44 • 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.
|
|
Psychiatric disorders
Depression
|
13.6%
6/44 • 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.
|
|
Psychiatric disorders
Anxiety
|
11.4%
5/44 • 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.
|
|
Psychiatric disorders
Insomnia
|
11.4%
5/44 • 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.
|
|
Renal and urinary disorders
Dysuria
|
6.8%
3/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.5%
9/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.9%
7/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
6.8%
3/44 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
6.8%
3/44 • 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.
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
15.9%
7/44 • 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.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.1%
4/44 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER