Trial Outcomes & Findings for A Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Participants With Advanced Solid Tumors (NCT NCT00500903)
NCT ID: NCT00500903
Last Updated: 2019-03-14
Results Overview
DLT was evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and was defined as any of the following events related to therapy with alisertib: 1. Grade 4 neutropenia lasting ≥7 consecutive days 2. Grade 4 neutropenia with fever and/or infection 3. Platelet count \<25,000/mm\^3 4. Grade 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis 5. Grade 3 or greater diarrhea despite maximal supportive therapy with loperamide 6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (\<1 week) Grade 3 fatigue 7. Treatment delay of \>1 week due to failure of adequate hematologic or nonhematologic recovery from previous cycle of treatment 8. Other alisertib-related nonhematologic toxicities ≥Grade 2 that, in the opinion of the investigator, required a dose reduction or discontinuation of therapy with alisertib.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
87 participants
Primary outcome timeframe
Cycle 1 Day 1 up to Day 35 (alisertib daily for 7 to 21 days followed by a 14-day recovery period)
Results posted on
2019-03-14
Participant Flow
Participants took part in the study at 3 investigative sites in the United States from 15 May 2007 to 23 February 2011.
Participants with a diagnosis of advanced malignancies were enrolled in 1 of 3 treatment groups, alisertib 5 to 150 mg Powder-in-Capsule (PIC) dose escalation cohort, alisertib 10 or 20 mg Enteric-coated Tablet (ECT) dose escalation cohort, or alisertib 40 mg PIC/ECT in a crossover design followed by alisertib 50 mg relative bioavailability cohort.
Participant milestones
| Measure |
PIC Dose Escalation
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
ECT Dose Escalation
Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Relative Bioavailability
Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 9 cycles).
|
|---|---|---|---|
|
Overall Study
STARTED
|
65
|
2
|
20
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
65
|
2
|
20
|
Reasons for withdrawal
| Measure |
PIC Dose Escalation
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
ECT Dose Escalation
Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Relative Bioavailability
Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 9 cycles).
|
|---|---|---|---|
|
Overall Study
Occurrence of Adverse Event(s)
|
10
|
0
|
0
|
|
Overall Study
Unsatisfactory Therapeutic Response
|
2
|
0
|
0
|
|
Overall Study
Progressive Disease
|
41
|
2
|
15
|
|
Overall Study
Patient Declined Further Treatment
|
0
|
0
|
3
|
|
Overall Study
Symptomatic Deterioration
|
2
|
0
|
0
|
|
Overall Study
Reason Not Specified
|
10
|
0
|
2
|
Baseline Characteristics
A Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Participants With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
PIC Dose Escalation
n=65 Participants
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
ECT Dose Escalation
n=2 Participants
Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Relative Bioavailability
n=20 Participants
Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 9 cycles).
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
61.6 years
STANDARD_DEVIATION 10.44 • n=5 Participants
|
57.0 years
STANDARD_DEVIATION 15.56 • n=7 Participants
|
56.9 years
STANDARD_DEVIATION 11.71 • n=5 Participants
|
60.4 years
STANDARD_DEVIATION 10.88 • n=4 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
56 participants
n=5 Participants
|
2 participants
n=7 Participants
|
20 participants
n=5 Participants
|
78 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
7 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
55 participants
n=5 Participants
|
2 participants
n=7 Participants
|
18 participants
n=5 Participants
|
75 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
9 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
11 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
65 participants
n=5 Participants
|
2 participants
n=7 Participants
|
20 participants
n=5 Participants
|
87 participants
n=4 Participants
|
|
Height
|
169.3 cm
STANDARD_DEVIATION 10.06 • n=5 Participants
|
165.1 cm
STANDARD_DEVIATION 0.00 • n=7 Participants
|
171.5 cm
STANDARD_DEVIATION 12.51 • n=5 Participants
|
169.7 cm
STANDARD_DEVIATION 10.55 • n=4 Participants
|
|
Weight
|
78.24 kg
STANDARD_DEVIATION 18.130 • n=5 Participants
|
67.36 kg
STANDARD_DEVIATION 11.226 • n=7 Participants
|
83.97 kg
STANDARD_DEVIATION 21.706 • n=5 Participants
|
79.33 kg
STANDARD_DEVIATION 18.976 • n=4 Participants
|
|
Body Surface Area (BSA)
|
1.91 m^2
STANDARD_DEVIATION 0.263 • n=5 Participants
|
1.75 m^2
STANDARD_DEVIATION 0.147 • n=7 Participants
|
1.99 m^2
STANDARD_DEVIATION 0.294 • n=5 Participants
|
1.92 m^2
STANDARD_DEVIATION 0.270 • n=4 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 Day 1 up to Day 35 (alisertib daily for 7 to 21 days followed by a 14-day recovery period)Population: DLT-Evaluable Population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.
DLT was evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and was defined as any of the following events related to therapy with alisertib: 1. Grade 4 neutropenia lasting ≥7 consecutive days 2. Grade 4 neutropenia with fever and/or infection 3. Platelet count \<25,000/mm\^3 4. Grade 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis 5. Grade 3 or greater diarrhea despite maximal supportive therapy with loperamide 6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (\<1 week) Grade 3 fatigue 7. Treatment delay of \>1 week due to failure of adequate hematologic or nonhematologic recovery from previous cycle of treatment 8. Other alisertib-related nonhematologic toxicities ≥Grade 2 that, in the opinion of the investigator, required a dose reduction or discontinuation of therapy with alisertib.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
n=3 Participants
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
n=3 Participants
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
n=6 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
n=7 Participants
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
n=11 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
n=2 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
n=1 Participants
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
n=1 Participants
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Dose-Limiting Toxicity (DLT)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
3 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
2 participants
|
2 participants
|
2 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: From first dose of study drug to 30 days after the last dose (up to 1011 days)Population: DLT-Evaluable Population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.
MTD was defined as the highest dose at which DLT occurred in 0/3 or 1/6 patients.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=65 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of Alisertib
|
—
|
50 mg BID for 7 Days
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug to 30 days after the last dose (up to 1011 days)Population: Safety Population included all participants who received any amount of study drug.
An Adverse Event (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. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=65 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=20 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
2 participants
|
65 participants
|
20 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 participants
|
26 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Day 1
|
279.1 nM
Geometric Coefficient of Variation 46.20
|
208.4 nM
Geometric Coefficient of Variation 27.96
|
759.3 nM
Geometric Coefficient of Variation 11.82
|
1245.4 nM
Geometric Coefficient of Variation 20.60
|
1661.3 nM
Geometric Coefficient of Variation 45.20
|
2717.8 nM
Geometric Coefficient of Variation 44.62
|
4260.3 nM
Geometric Coefficient of Variation 42.62
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Day 7
|
931.5 nM
Geometric Coefficient of Variation 81.68
|
285.7 nM
Geometric Coefficient of Variation 32.74
|
1114.1 nM
Geometric Coefficient of Variation 36.96
|
1681.6 nM
Geometric Coefficient of Variation 64.62
|
2376.3 nM
Geometric Coefficient of Variation 51.06
|
3586.4 nM
Geometric Coefficient of Variation 48.28
|
4467.8 nM
Geometric Coefficient of Variation 24.58
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Day 1
|
2.000 hours (h)
Interval 1.5 to 3.0
|
2.000 hours (h)
Interval 1.5 to 3.0
|
1.500 hours (h)
Interval 1.5 to 1.5
|
2.000 hours (h)
Interval 1.5 to 6.0
|
2.000 hours (h)
Interval 1.5 to 3.0
|
2.000 hours (h)
Interval 1.48 to 5.57
|
2.000 hours (h)
Interval 1.45 to 3.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Day 7
|
3.750 hours (h)
Interval 1.5 to 6.0
|
1.500 hours (h)
Interval 1.0 to 1.5
|
1.500 hours (h)
Interval 1.5 to 2.0
|
2.000 hours (h)
Interval 1.97 to 6.0
|
2.000 hours (h)
Interval 1.98 to 3.05
|
3.710 hours (h)
Interval 1.42 to 6.02
|
2.000 hours (h)
Interval 1.48 to 3.93
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUCt: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Day 1
|
2525.8 nM*h
Geometric Coefficient of Variation 21.87
|
1682.4 nM*h
Geometric Coefficient of Variation 31.06
|
5772.1 nM*h
Geometric Coefficient of Variation 10.68
|
12045.4 nM*h
Geometric Coefficient of Variation 57.01
|
20958.1 nM*h
Geometric Coefficient of Variation 38.92
|
29460.7 nM*h
Geometric Coefficient of Variation 39.43
|
38582.1 nM*h
Geometric Coefficient of Variation 45.95
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
AUCt: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Day 7
|
10602.9 nM*h
Geometric Coefficient of Variation 107.87
|
2919.5 nM*h
Geometric Coefficient of Variation 32.31
|
10927.5 nM*h
Geometric Coefficient of Variation 45.27
|
21976.0 nM*h
Geometric Coefficient of Variation 96.64
|
27825.5 nM*h
Geometric Coefficient of Variation 53.59
|
46271.1 nM*h
Geometric Coefficient of Variation 33.38
|
53031.9 nM*h
Geometric Coefficient of Variation 26.22
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=2 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=2 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=5 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Half-Life (t1/2) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
|
35.150 h
Standard Deviation 23.4052
|
24.950 h
Standard Deviation 20.4354
|
26.400 h
Standard Deviation 19.7684
|
18.155 h
Standard Deviation 12.5087
|
39.333 h
Standard Deviation 18.8006
|
13.427 h
Standard Deviation 4.3465
|
16.766 h
Standard Deviation 9.7804
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=2 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=5 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
|
6.350 ratio
Standard Deviation 7.2408
|
1.753 ratio
Standard Deviation 0.2754
|
2.037 ratio
Standard Deviation 0.9708
|
1.997 ratio
Standard Deviation 0.9393
|
1.535 ratio
Standard Deviation 0.3323
|
1.677 ratio
Standard Deviation 0.6788
|
1.588 ratio
Standard Deviation 0.4129
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=5 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
|
5.195 ratio
Standard Deviation 3.9527
|
4.107 ratio
Standard Deviation 0.8460
|
5.430 ratio
Standard Deviation 2.4856
|
3.907 ratio
Standard Deviation 2.3944
|
3.850 ratio
Standard Deviation 2.0612
|
4.922 ratio
Standard Deviation 2.5890
|
4.610 ratio
Standard Deviation 0.5314
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=5 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
|
1.817 liters (L)/h
Geometric Coefficient of Variation 107.8347
|
3.302 liters (L)/h
Geometric Coefficient of Variation 35.8915
|
3.525 liters (L)/h
Geometric Coefficient of Variation 49.1267
|
3.511 liters (L)/h
Geometric Coefficient of Variation 72.1346
|
5.545 liters (L)/h
Geometric Coefficient of Variation 41.0258
|
4.348 liters (L)/h
Geometric Coefficient of Variation 61.5266
|
5.450 liters (L)/h
Geometric Coefficient of Variation 37.3021
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=2 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=6 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
|
0.0 ng
Standard Deviation 0.00
|
0.0 ng
Standard Deviation 0.00
|
0.0 ng
Standard Deviation 0.00
|
4806.7 ng
Standard Deviation 8325.39
|
18815.0 ng
Standard Deviation 1675.84
|
13813.3 ng
Standard Deviation 16387.22
|
14473.3 ng
Standard Deviation 15603.71
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=1 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=1 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=5 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=5 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
|
0.0013860 L/h
Standard Deviation NA
Cannot be calculated for 1 participant
|
0.0012630 L/h
Standard Deviation NA
Cannot be calculated for 1 participant
|
0.0009414 L/h
Standard Deviation 0.00063956
|
0.0006710 L/h
Standard Deviation 0.00060091
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 1
|
—
|
778.7 nM
Geometric Coefficient of Variation 24.28
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 7
|
—
|
995.5 nM
Geometric Coefficient of Variation 43.21
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 14
|
—
|
808.9 nM
Geometric Coefficient of Variation 37.96
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
—
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—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 14
|
—
|
2.000 h
Interval 1.098 to 2.0
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 1
|
—
|
4.000 h
Interval 2.0 to 8.88
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 7
|
—
|
2.000 h
Interval 2.0 to 2.0
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUCt: Area Under the Concentration--Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 1
|
—
|
8061.6 nM*h
Geometric Coefficient of Variation 17.30
|
—
|
—
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—
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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|
AUCt: Area Under the Concentration--Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 7
|
—
|
8634.0 nM*h
Geometric Coefficient of Variation 42.70
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
AUCt: Area Under the Concentration--Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 14
|
—
|
8978.0 nM*h
Geometric Coefficient of Variation 20.15
|
—
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—
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—
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—
|
—
|
—
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—
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—
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—
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—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 14 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Half-Life for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
|
—
|
65.67 h
Standard Deviation 43.859
|
—
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—
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—
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—
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—
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—
|
—
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—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Days 7 and 14 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 7
|
—
|
1.203 ratio
Standard Deviation 0.6964
|
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 14
|
—
|
1.133 ratio
Standard Deviation 0.2303
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Days 7 and 14 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 7
|
—
|
6.877 ratio
Standard Deviation 1.1151
|
—
|
—
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 14
|
—
|
5.073 ratio
Standard Deviation 2.2113
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
SECONDARY outcome
Timeframe: Cycle 1 Days 7 and 14 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 7
|
—
|
6.030 L/h
Standard Deviation 2.9963
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
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—
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—
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—
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—
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—
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|
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Day 14
|
—
|
5.433 L/h
Standard Deviation 0.9808
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
|
—
|
800.0 ng
Standard Deviation 1385.64
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=1 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
|
—
|
0.0004930 L/h
Standard Deviation NA
Cannot be calculated for 1 participant
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple timepoints up to 24 hours postdose and Days 14 and 21 predose and at multiple time points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 1
|
1725.9 nM
Geometric Coefficient of Variation 54.70
|
898.2 nM
Geometric Coefficient of Variation 86.35
|
2237.0 nM
Geometric Coefficient of Variation 54.18
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 14
|
1722.0 nM
Geometric Coefficient of Variation 38.82
|
1343.3 nM
Geometric Coefficient of Variation 60.32
|
2598.3 nM
Geometric Coefficient of Variation 12.49
|
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 21
|
1564.2 nM
Geometric Coefficient of Variation 38.80
|
1104.7 nM
Geometric Coefficient of Variation 45.15
|
1974.5 nM
Geometric Coefficient of Variation 59.49
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple timepoints up to 24 hours postdose and Days 14 and 21 predose and at multiple time points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 1
|
2.285 h
Interval 2.0 to 4.0
|
2.020 h
Interval 2.0 to 4.0
|
2.000 h
Interval 2.0 to 2.02
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 14
|
2.000 h
Interval 1.98 to 2.03
|
2.000 h
Interval 2.0 to 2.18
|
2.000 h
Interval 2.0 to 2.05
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 21
|
2.000 h
Interval 1.93 to 9.92
|
2.000 h
Interval 1.0 to 2.02
|
2.000 h
Interval 1.0 to 6.0
|
—
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—
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—
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—
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—
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—
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—
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—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple timepoints up to 24 hours postdose and Days 14 and 21 predose and at multiple time points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 1
|
14686.6 nM*h
Geometric Coefficient of Variation 44.04
|
10058.0 nM*h
Geometric Coefficient of Variation 66.85
|
22114.8 nM*h
Geometric Coefficient of Variation 68.66
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 14
|
17168.2 nM*h
Geometric Coefficient of Variation 32.09
|
15131.7 nM*h
Geometric Coefficient of Variation 49.89
|
23197.2 nM*h
Geometric Coefficient of Variation 17.75
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 21
|
19336.3 nM*h
Geometric Coefficient of Variation 26.85
|
13199.3 nM*h
Geometric Coefficient of Variation 70.05
|
23499.8 nM*h
Geometric Coefficient of Variation 65.64
|
—
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—
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—
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—
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—
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—
|
—
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—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 21 predose and at multiple time points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=5 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Half-Life (t1/2) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
|
23.650 h
Standard Deviation 16.9487
|
31.667 h
Standard Deviation 6.7122
|
22.378 h
Standard Deviation 19.8802
|
—
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—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Days 14 and 21 predose and at multiple timepoints (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 14
|
1.230 ratio
Standard Deviation 0.4193
|
1.560 ratio
Standard Deviation 0.5543
|
1.440 ratio
Standard Deviation 0.1493
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
|
Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 21
|
1.373 ratio
Standard Deviation 0.4474
|
1.560 ratio
Standard Deviation 1.0516
|
1.335 ratio
Standard Deviation 0.4749
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
SECONDARY outcome
Timeframe: Cycle 1 Days 14 and 21 predose and at multiple timepoints up to 10 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 14
|
7.543 ratio
Standard Deviation 5.4982
|
4.773 ratio
Standard Deviation 0.9001
|
6.392 ratio
Standard Deviation 2.0824
|
—
|
—
|
—
|
—
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—
|
—
|
—
|
—
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—
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—
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—
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—
|
—
|
|
Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 21
|
4.157 ratio
Standard Deviation 2.1051
|
3.637 ratio
Standard Deviation 1.8675
|
5.570 ratio
Standard Deviation 2.5772
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
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—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Days 14 and 21 predose and at multiple timepoints up to 10 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 14
|
5.612 L/h
Geometric Coefficient of Variation 28.6881
|
3.181 L/h
Geometric Coefficient of Variation 42.5706
|
5.825 L/h
Geometric Coefficient of Variation 17.7291
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Day 21
|
4.984 L/h
Geometric Coefficient of Variation 25.6945
|
3.656 L/h
Geometric Coefficient of Variation 89.5750
|
5.745 L/h
Geometric Coefficient of Variation 42.3818
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
|
5766.7 ng
Standard Deviation 7971.95
|
3047.7 ng
Standard Deviation 5278.71
|
9391.4 ng
Standard Deviation 11410.18
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=1 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=4 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
|
0.0012323 L/h
Standard Deviation 0.00111840
|
0.0008640 L/h
Standard Deviation NA
Cannot be calculated for 1 participant
|
0.0007865 L/h
Standard Deviation 0.00042447
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=11 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Day 1
|
1867.1 nM
Geometric Coefficient of Variation 29.03
|
1581.1 nM
Geometric Coefficient of Variation 37.34
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Day 7
|
3080.8 nM
Geometric Coefficient of Variation 38.79
|
3376.4 nM
Geometric Coefficient of Variation 41.74
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=11 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Day 1
|
2.000 h
Interval 1.6 to 4.0
|
2.000 h
Interval 1.98 to 8.0
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Day 7
|
2.000 h
Interval 1.98 to 6.03
|
2.015 h
Interval 0.98 to 6.05
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=11 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Day 1
|
13200.4 nM*h
Geometric Coefficient of Variation 26.70
|
11166.3 nM*h
Geometric Coefficient of Variation 37.45
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Day 7
|
27386.1 nM*h
Geometric Coefficient of Variation 37.43
|
32291.5 nM*h
Geometric Coefficient of Variation 40.82
|
—
|
—
|
—
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—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8Population: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=10 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Half-Life (t1/2) for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
|
18.200 h
Standard Deviation 3.2212
|
20.215 h
Standard Deviation 15.5083
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=3 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=5 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
|
2.543 ratio
Standard Deviation 0.1950
|
2.474 ratio
Standard Deviation 1.0467
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=4 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=6 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
|
1.890 ratio
Standard Deviation 0.2012
|
2.193 ratio
Standard Deviation 1.1346
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SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=4 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=5 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
|
4.220 L/h
Geometric Coefficient of Variation 47.9681
|
2.984 L/h
Geometric Coefficient of Variation 43.8719
|
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=5 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=10 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
|
8498.3 ng
Standard Deviation 6866.09
|
13775.0 ng
Standard Deviation 7937.14
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=5 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=10 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
|
0.001 ng
Standard Deviation 0.0004
|
0.001 ng
Standard Deviation 0.0011
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Days 1 and 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=2 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Day 1
|
—
|
1236.6 nM
Geometric Coefficient of Variation 37.29
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Day 7
|
—
|
2060.0 nM
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation cannot be calculated for 1 participant.
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
SECONDARY outcome
Timeframe: Cycle 1 Days 1 and 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=2 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Day 1
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—
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3.00 h
Interval 2.0 to 4.0
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Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Day 7
|
—
|
1.70 h
Interval 1.7 to 1.7
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SECONDARY outcome
Timeframe: Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=2 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
|
—
|
9684.8 nM*h
Geometric Coefficient of Variation 71.50
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=14 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=14 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUCt: Area Under the Concentration-time Curve From Time 0 to Time t as Assessment of Relative Bioavailability for Alisertib as Enteric-coated Tablet (ECT) Versus PIC at Day 7
|
14190.7 nM*h
Standard Deviation 7097.72
|
12700.0 nM*h
Standard Deviation 6557.58
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=14 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=14 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Cmax: Maximum Observed Concentration as Assessment of Relative Bioavailability for Alisertib as Enteric-coated Tablet (ECT) Versus PIC at Day 7
|
2027.9 nM
Standard Deviation 928.96
|
1666.1 nM
Standard Deviation 765.28
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-points.
Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers-serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=5 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 7 Days (QD7D) Dosing
Day 1, Hour 6
|
0.614 mitotic cells/millimeter of BEL
Standard Deviation 0.5437
|
0.405 mitotic cells/millimeter of BEL
Standard Deviation 0.2701
|
0.263 mitotic cells/millimeter of BEL
Standard Deviation 0.1461
|
0.168 mitotic cells/millimeter of BEL
Standard Deviation 0.5146
|
0.488 mitotic cells/millimeter of BEL
Standard Deviation 1.0215
|
0.261 mitotic cells/millimeter of BEL
Standard Deviation 0.4597
|
0.865 mitotic cells/millimeter of BEL
Standard Deviation 0.9420
|
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—
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—
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—
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—
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—
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Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 7 Days (QD7D) Dosing
Day 1, Hour 24
|
-0.103 mitotic cells/millimeter of BEL
Standard Deviation 0.0186
|
0.019 mitotic cells/millimeter of BEL
Standard Deviation 0.1914
|
0.005 mitotic cells/millimeter of BEL
Standard Deviation 0.0709
|
0.141 mitotic cells/millimeter of BEL
Standard Deviation 0.3852
|
0.108 mitotic cells/millimeter of BEL
Standard Deviation 0.4081
|
1.764 mitotic cells/millimeter of BEL
Standard Deviation 2.6380
|
0.239 mitotic cells/millimeter of BEL
Standard Deviation 0.6992
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-points.
Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=2 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=3 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
n=3 Participants
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
n=3 Participants
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
n=5 Participants
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
n=6 Participants
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 7 Days (QD7D) Dosing
Day 1, Hour 6
|
-0.090 apoptotic cells/millimeter of BEL
Standard Deviation 0.1278
|
0.010 apoptotic cells/millimeter of BEL
Standard Deviation 0.1175
|
0.042 apoptotic cells/millimeter of BEL
Standard Deviation 0.0731
|
0.040 apoptotic cells/millimeter of BEL
Standard Deviation 0.0701
|
0.121 apoptotic cells/millimeter of BEL
Standard Deviation 0.1317
|
0.036 apoptotic cells/millimeter of BEL
Standard Deviation 0.0530
|
-0.042 apoptotic cells/millimeter of BEL
Standard Deviation 0.1262
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 7 Days (QD7D) Dosing
Day 1, Hour 24
|
0.065 apoptotic cells/millimeter of BEL
Standard Deviation 0.1404
|
0.009 apoptotic cells/millimeter of BEL
Standard Deviation 0.1164
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation 0.0000
|
0.037 apoptotic cells/millimeter of BEL
Standard Deviation 0.0634
|
0.074 apoptotic cells/millimeter of BEL
Standard Deviation 0.1286
|
0.151 apoptotic cells/millimeter of BEL
Standard Deviation 0.1721
|
0.139 apoptotic cells/millimeter of BEL
Standard Deviation 0.2069
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-points.
Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers-serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 14 Days (QD14D) Dosing
Day 1, Hour 6
|
—
|
0.134 mitotic cells/millimeter of BEL
Standard Deviation 0.1723
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 14 Days (QD14D) Dosing
Day 1, Hour 24
|
—
|
0.047 mitotic cells/millimeter of BEL
Standard Deviation 0.0589
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-points.
Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 14 Days (QD14D) Dosing
Day 1, Hour 6
|
—
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation 0.0000
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 14 Days (QD14D) Dosing
Day 1, Hour 24
|
—
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation 0.0000
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Days 7 and 21, 6 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers-serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 1, Hour 6
|
0.405 mitotic cells/millimeter of BEL
Standard Deviation 0.4690
|
0.380 mitotic cells/millimeter of BEL
Standard Deviation 0.4165
|
0.510 mitotic cells/millimeter of BEL
Standard Deviation NA
Cannot be calculated for 1 participant
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 1, Hour 24
|
0.082 mitotic cells/millimeter of BEL
Standard Deviation 0.1796
|
0.021 mitotic cells/millimeter of BEL
Standard Deviation 0.1081
|
0.289 mitotic cells/millimeter of BEL
Standard Deviation 0.5746
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 7, Hour 6
|
—
|
—
|
0.479 mitotic cells/millimeter of BEL
Standard Deviation 0.3040
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 21, Hour 6
|
0.045 mitotic cells/millimeter of BEL
Standard Deviation NA
Cannot be calculated for 1 participant.
|
—
|
0.742 mitotic cells/millimeter of BEL
Standard Deviation 0.5782
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Days 7 and 21, 6 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=3 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
n=7 Participants
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 1, Hour 6
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation 0.0000
|
0.122 apoptotic cells/millimeter of BEL
Standard Deviation 0.2117
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation NA
Cannot be calculated for 1 participant
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 1, Hour 24
|
0.042 apoptotic cells/millimeter of BEL
Standard Deviation 0.0719
|
0.042 apoptotic cells/millimeter of BEL
Standard Deviation 0.0722
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation 0.0000
|
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 7, Hour 6
|
—
|
—
|
0.000 apoptotic cells/millimeter of BEL
Standard Deviation 0.0000
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Day 21, Hour 6
|
0.099 apoptotic cells/millimeter of BEL
Standard Deviation NA
Cannot be calculated for 1 participant.
|
—
|
0.032 apoptotic cells/millimeter of BEL
Standard Deviation 0.0552
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Day 7, 6 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers-serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=11 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Day 1, Hour 6
|
0.364 mitotic cells/millimeter of BEL
Standard Deviation 0.2574
|
0.054 mitotic cells/millimeter of BEL
Standard Deviation 0.3022
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Day 1, Hour 24
|
1.435 mitotic cells/millimeter of BEL
Standard Deviation 0.8329
|
2.578 mitotic cells/millimeter of BEL
Standard Deviation 2.2875
|
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Day 7, Hour 6
|
—
|
5.486 mitotic cells/millimeter of BEL
Standard Deviation 5.8688
|
—
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—
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—
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—
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—
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—
|
—
|
—
|
—
|
—
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—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Day 7, 6 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
n=6 Participants
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=11 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Day 1, Hour 6
|
0.020 apoptotic cells/millimeter of BEL
Standard Deviation 0.0491
|
-0.016 apoptotic cells/millimeter of BEL
Standard Deviation 0.0494
|
—
|
—
|
—
|
—
|
—
|
—
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—
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—
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—
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—
|
—
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—
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—
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—
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|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Day 1, Hour 24
|
0.080 apoptotic cells/millimeter of BEL
Standard Deviation 0.1958
|
0.055 apoptotic cells/millimeter of BEL
Standard Deviation 0.1691
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Day 7, Hour 6
|
—
|
2.142 apoptotic cells/millimeter of BEL
Standard Deviation 3.2510
|
—
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—
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—
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—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 7, 6 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers-serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=1 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Twice Daily for 14 Days (BID14D) Dosing
|
—
|
1.507 mitotic cells/millimeter of BEL
Standard Deviation NA
Cannot be calculated for 1 participant
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Cycle 1 Day 7, 6 hours postdosePopulation: Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time-point.
Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=1 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Twice Daily for 14 Days (BID14D) Dosing
|
—
|
2.837 apoptotic cells/millimeter of BEL
Standard Deviation NA
Cannot be calculated for 1 participant
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1 predosePopulation: Safety Population included all participants who received any amount of study drug.
One peripheral blood sample (approximately 4 mL) was to be obtained on Day 1 of Cycle 1 prior to the first dose of alisertib to genotype patients for polymorphisms in UGT1A1 because UGT1A1 is one of the enzymes responsible for glucuronidation of alisertib, which is expected to contribute to the clearance of alisertib. wt=wild type \*28=polymorphism in the promoter region of a UGT1A1 allele resulting in reduced UGT1A1 expression.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=87 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
wt/wt
|
—
|
38 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
wt/*28
|
—
|
30 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
*28/*28
|
—
|
9 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
*28/other
|
—
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
other/other
|
—
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
Not Determined
|
—
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
Missing
|
—
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Beginning at the end of Cycle 2, every 2 cycles until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU) every 8-12 weeks until PD or as per institutional practice (Up to 33.2 months)Population: Safety Population included all participants who received any amount of study drug.
Best overall response is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. According to RECIST: CR is defined as disappearance of all target and nontarget lesions and normalization of tumor marker level (if applicable); PR is defined as ≥30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, persistence of 1 or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=87 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Best Overall Response Based on Investigator Assessment
|
—
|
1 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Beginning at the end of Cycle 2, every 2 cycles until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU) every 8-12 weeks until PD or as per institutional practice (Up to 33.2 months)Population: Safety Population included all participants who received any amount of study drug.
DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 50 mg PIC BID 7D
n=1 Participants
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 20 mg PIC QD 7D
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
|
Alisertib 40 mg PIC QD 7D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
|
Alisertib 80 mg PIC QD 7D
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
|
Alisertib 110 mg PIC QD 7D
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 150 mg PIC QD 7D
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
Alisertib 25 mg PIC QD 14D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
|
Alisertib 25 mg PIC QD 21D
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
|
Alisertib 50 mg PIC QD 21D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
|
Alisertib 70 mg PIC QD 21D
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 50 mg PIC BID 7D
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
|
Alisertib 60 mg PIC BID 7D
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
|
Alisertib 40 mg PIC BID 14D
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
|
Alisertib 10 mg ECT QD7
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Alisertib 20 mg ECT QD7
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration Of Response (DOR)
|
—
|
470 days
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: The effects of food on the PK of alisertib was not conducted. As the development of alisertib was transitioned from the PIC to the ECT formulation and the clinical dose of alisertib ECT had not been determined yet, it was decided that the effect of food would be evaluated in a different study at the appropriate clinical dose, administered as ECT.
The effects of food on the PK of alisertib were to be evaluated using the preferred alisertib regimen (unit dose and formulation) based on the results from the relative bioavailability study.
Outcome measures
Outcome data not reported
Adverse Events
PIC Dose Escalation
Serious events: 26 serious events
Other events: 65 other events
Deaths: 0 deaths
ECT Dose Escalation
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Relative Bioavailability
Serious events: 1 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PIC Dose Escalation
n=65 participants at risk
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
ECT Dose Escalation
n=2 participants at risk
Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Relative Bioavailability
n=20 participants at risk
Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 9 cycles).
|
|---|---|---|---|
|
Cardiac disorders
Ventricular dysfunction
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Arrhythmia supraventricular
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Atrial fibrillation
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Intestinal obstruction
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 obstruction
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Gastrointestinal haemorrhage
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Febrile neutropenia
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Neutropenia
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Thrombocytopenia
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Klebsiella bacteraemia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Enterococcal bacteraemia
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Pneumonia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Staphylococcal infection
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Bacteraemia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hyperbilirubinaemia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Jaundice cholestatic
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 stenosis
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Asthenia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Disease progression
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Syncope
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Mental impairment
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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)
Metastases to central nervous system
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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)
Pancreatic carcinoma metastatic
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Pulmonary embolism
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Restrictive cardiomyopathy
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Radius fracture
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Neck pain
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hallucination, visual
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Renal failure acute
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 |
PIC Dose Escalation
n=65 participants at risk
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
|
ECT Dose Escalation
n=2 participants at risk
Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 2 cycles).
|
Relative Bioavailability
n=20 participants at risk
Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14--day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14--day recovery period in each cycle until disease progression or unacceptable alisertib--related toxicity (up to 9 cycles).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
15.0%
3/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Anorexia
|
46.2%
30/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
15.0%
3/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
13.8%
9/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
60.0%
39/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
30.0%
6/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
52.3%
34/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
30.0%
6/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
36.9%
24/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
23.1%
15/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
25.0%
5/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
18.5%
12/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
20.0%
4/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
20.0%
13/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Flatulence
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hypokalaemia
|
12.3%
8/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 distension
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Ascites
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Oral pain
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 lower
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 discomfort
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Frequent bowel movements
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Gastrooesophageal reflux disease
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Gingival pain
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
49.2%
32/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
100.0%
2/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
60.0%
12/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
20.0%
13/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
20.0%
4/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
18.5%
12/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
25.0%
5/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Asthenia
|
16.9%
11/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Chest discomfort
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Pain
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Malaise
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Catheter site inflammation
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Irritability
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Somnolence
|
41.5%
27/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
30.0%
6/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
20.0%
13/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
15.0%
3/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
13.8%
9/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Paraesthesia
|
9.2%
6/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Peripheral sensory neuropathy
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Grand mal convulsion
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Neutropenia
|
43.1%
28/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
35.0%
7/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
36.9%
24/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
100.0%
2/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
30.0%
6/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Thrombocytopenia
|
12.3%
8/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Leukopenia
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
20.0%
4/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
10.8%
7/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hypocalcaemia
|
10.8%
7/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hyponatraemia
|
10.8%
7/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hyperkalaemia
|
9.2%
6/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hypernatraemia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hypomagnesaemia
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Alopecia
|
38.5%
25/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
10/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Dermatitis acneiform
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hyperhidrosis
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Onychorrhexis
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Swelling face
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Urticaria
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
White blood cell count decreased
|
32.3%
21/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
15.0%
3/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Blood alkaline phosphatase increased
|
9.2%
6/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Blood creatinine increased
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
9.2%
6/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Alanine aminotransferase increased
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Aspartate aminotransferase increased
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Platelet count decreased
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 increased
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Blood bilirubin increased
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Neutrophil count decreased
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Activated partial thromboplastin time prolonged
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Blood sodium decreased
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
9.2%
6/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Shoulder pain
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Neck pain
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
15.0%
3/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Chest wall pain
|
3.1%
2/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Joint swelling
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Groin pain
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
15.4%
10/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
13.8%
9/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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 exertional
|
7.7%
5/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
50.0%
1/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Rhinorrhoea
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Pharyngolaryngeal pain
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
9.2%
6/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Escherichia infection
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Folliculitis
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
10.8%
7/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
15.0%
3/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Confusional state
|
4.6%
3/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Agitation
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Mood altered
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hot flush
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hypotension
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Pollakiuria
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
10.0%
2/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Eye swelling
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Visual disturbance
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Atrial flutter
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
|
Ear and labyrinth disorders
Ear pain
|
1.5%
1/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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
Hepatobiliary disorders
|
6.2%
4/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/65 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
0.00%
0/2 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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.
|
5.0%
1/20 • From first dose of study drug to 30 days after the last dose (up to 1011 days)
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