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A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Alisertib in Participants With Advanced Solid Tumors or Relapsed/Refractory Lymphoma

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ClinicalTrials.gov Identifier: NCT02259010
Recruitment Status : Completed
First Posted : October 8, 2014
Results First Posted : September 20, 2019
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Conditions Advanced Solid Tumors
Relapsed/Refractory Lymphoma
Interventions Drug: Alisertib
Drug: Itraconazole
Enrollment 24
Recruitment Details Participants took part in the study at 4 investigative sites in the United States from 22 October 2014 to 21 October 2016. Data cutoff for the primary analysis was 27 March 2015.
Pre-assignment Details Participants with a diagnosis of advanced solid tumors or lymphomas were enrolled to receive alisertib 30 mg tablets, orally along with itraconazole 200 mg, oral solution in part A followed by alisertib 50 mg, tablets in part B.
Arm/Group Title Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Hide Arm/Group Description All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
Period Title: Overall Study
Started 24
Completed 19 [1]
Not Completed 5
Reason Not Completed
Didn't Completed Dosing; PK Assessment             5
[1]
Completed=Completed protocol-specified dosing and PK assessment.
Arm/Group Title Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Hide Arm/Group Description All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
Safety Population is defined as all participants who received at least 1 dose of any study drug and was used for all safety analyses.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
61.0  (9.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
13
  54.2%
Male
11
  45.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Hispanic or Latino
1
   4.2%
Not Hispanic or Latino
20
  83.3%
Not Reported
3
  12.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
White
20
  83.3%
Black or African American
2
   8.3%
Asian
1
   4.2%
Other
1
   4.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 24 participants
168.3  (8.99)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 24 participants
85.55  (25.641)
Body Surface Area   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 24 participants
1.983  (0.3024)
[1]
Measure Description: Body surface area=square root of (height [cm]*weight [kg]/3600).
1.Primary Outcome
Title Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) -Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: nmol/L
1060.3  (403.90) 1002.8  (263.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Itraconazole, Alisertib With Itraconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Ratio
Estimated Value 0.98
Confidence Interval (2-Sided) 90%
0.82 to 1.19
Estimation Comments Estimates were obtained using a mixed effects model of log (PK parameter) with fixed terms for the itraconazole effect and random terms for participant within period.
2.Primary Outcome
Title AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 19 19
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
15541.6  (9119.52) 20219.5  (9930.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Itraconazole, Alisertib With Itraconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Ratio
Estimated Value 1.35
Confidence Interval (2-Sided) 90%
1.02 to 1.79
Estimation Comments Estimates were obtained using a mixed effects model of log (PK parameter) with fixed terms for the itraconazole effect and random terms for participant within period.
3.Primary Outcome
Title AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here number of participants analyzed are the participants who were evaluable for this outcome measure at specified time points.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
16804.6  (9232.87) 23488.7  (13262.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib Without Itraconazole, Alisertib With Itraconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Ratio
Estimated Value 1.39
Confidence Interval (2-Sided) 90%
0.99 to 1.95
Estimation Comments Estimates were obtained using a mixed effects model of log (PK parameter) with fixed terms for the itraconazole effect and random terms for participant within period.
4.Secondary Outcome
Title CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: L/hr
4.416  (2.4007) 3.177  (1.5765)
5.Secondary Outcome
Title Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 19 19
Median (Full Range)
Unit of Measure: hr
2.920
(1.07 to 10.00)
2.920
(1.83 to 7.82)
6.Secondary Outcome
Title Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: hr
22.55  (10.316) 25.37  (9.215)
7.Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 18 19
Mean (Standard Deviation)
Unit of Measure: nmol/L
Metabolite 1 (M1) Number Analyzed 18 participants 18 participants
409.4  (479.92) 450.0  (664.65)
Metabolite 2 (M2) Number Analyzed 18 participants 19 participants
114.0  (52.71) 103.5  (99.28)
8.Secondary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 18 19
Median (Full Range)
Unit of Measure: hr
Metabolite 1 (M1) Number Analyzed 18 participants 18 participants
3.090
(1.00 to 23.10)
3.800
(1.98 to 10.00)
Metabolite 2 (M2) Number Analyzed 18 participants 19 participants
9.360
(2.95 to 47.70)
23.600
(5.73 to 95.30)
9.Secondary Outcome
Title AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
Arm/Group Title Alisertib Without Itraconazole Alisertib With Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .
Overall Number of Participants Analyzed 18 19
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
Metabolite 1 (M1) Number Analyzed 18 participants 18 participants
10550.8  (17276.38) 15776.1  (29461.34)
Metabolite 2 (M2) Number Analyzed 18 participants 19 participants
5880.6  (3404.27) 5081.6  (3334.41)
10.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
Arm/Group Title Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Hide Arm/Group Description:
All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
24
 100.0%
SAEs
12
  50.0%
11.Secondary Outcome
Title Number of Participants With Abnormal Laboratory Values Reported as AEs
Hide Description Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.
Time Frame First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
Arm/Group Title Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Hide Arm/Group Description:
All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Hypokalemia
3
  12.5%
Elevated blood creatinine
3
  12.5%
Increased international normalized ratio
2
   8.3%
Hypercalcemia
1
   4.2%
Hypomagnesemia
1
   4.2%
Hypoalbuminemia
1
   4.2%
Decreased blood potassium
1
   4.2%
Decreased blood sodium
1
   4.2%
Elevated blood alkaline phosphatase
1
   4.2%
Anemia
5
  20.8%
Neutropenia
4
  16.7%
Leukopenia
2
   8.3%
Thrombocytopenia
2
   8.3%
Decreased lymphocyte count
2
   8.3%
Decreased white blood cell count
1
   4.2%
Decreased platelet count
1
   4.2%
12.Secondary Outcome
Title Number of Participants With Clinically Significant Change in Weight Reported as AEs
Hide Description Change relative to baseline in participant's weight measured throughout study.
Time Frame First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
Arm/Group Title Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Hide Arm/Group Description:
All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
2
   8.3%
13.Secondary Outcome
Title Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs
Hide Description Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Time Frame First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
Arm/Group Title Alisertib Without Itraconazole
Hide Arm/Group Description:
Alisertib 30 mg, tablets, orally, on Day 1 in Part A.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Pyrexia
3
  12.5%
Palpitations
2
   8.3%
Tachycardia
1
   4.2%
Time Frame First dose of study drug up to 30 days after the last dose of study drug (up to 12 months)
Adverse Event Reporting Description Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
 
Arm/Group Title Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Hide Arm/Group Description All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
All-Cause Mortality
Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Affected / at Risk (%)
Total   1/24 (4.17%) 
Show Serious Adverse Events Hide Serious Adverse Events
Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Affected / at Risk (%)
Total   12/24 (50.00%) 
Blood and lymphatic system disorders   
Anaemia  1  2/24 (8.33%) 
Gastrointestinal disorders   
Abdominal pain  1  1/24 (4.17%) 
Constipation  1  1/24 (4.17%) 
Intestinal obstruction  1  1/24 (4.17%) 
Vomiting  1  1/24 (4.17%) 
Gastrointestinal haemorrhage  1  1/24 (4.17%) 
Melaena  1  1/24 (4.17%) 
Upper gastrointestinal haemorrhage  1  1/24 (4.17%) 
General disorders   
Gait disturbance  1  1/24 (4.17%) 
Disease progression  1  1/24 (4.17%) 
Infections and infestations   
Cellulitis  1  1/24 (4.17%) 
Herpes zoster disseminated  1  1/24 (4.17%) 
Pneumonia  1  1/24 (4.17%) 
Sepsis  1  1/24 (4.17%) 
Injury, poisoning and procedural complications   
Hip fracture  1  1/24 (4.17%) 
Metabolism and nutrition disorders   
Dehydration  1  1/24 (4.17%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/24 (4.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Glioblastoma  1 [1]  1/24 (4.17%) 
Nervous system disorders   
Haemorrhage intracranial  1  1/24 (4.17%) 
Psychiatric disorders   
Confusional state  1  1/24 (4.17%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/24 (4.17%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment and is not related with study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
Affected / at Risk (%)
Total   24/24 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  6/24 (25.00%) 
Neutropenia  1  6/24 (25.00%) 
Thrombocytopenia  1  4/24 (16.67%) 
Leukopenia  1  3/24 (12.50%) 
Cardiac disorders   
Palpitations  1  3/24 (12.50%) 
Eye disorders   
Vision blurred  1  2/24 (8.33%) 
Gastrointestinal disorders   
Nausea  1  11/24 (45.83%) 
Diarrhoea  1  10/24 (41.67%) 
Vomiting  1  8/24 (33.33%) 
Stomatitis  1  7/24 (29.17%) 
Constipation  1  6/24 (25.00%) 
Abdominal pain  1  4/24 (16.67%) 
Abdominal distension  1  3/24 (12.50%) 
Dyspepsia  1  3/24 (12.50%) 
Haemorrhoids  1  2/24 (8.33%) 
General disorders   
Fatigue  1  9/24 (37.50%) 
Oedema peripheral  1  6/24 (25.00%) 
Gait disturbance  1  3/24 (12.50%) 
Pyrexia  1  3/24 (12.50%) 
Chills  1  2/24 (8.33%) 
Infections and infestations   
Upper respiratory tract infection  1  3/24 (12.50%) 
Oral candidiasis  1  2/24 (8.33%) 
Urinary tract infection  1  2/24 (8.33%) 
Injury, poisoning and procedural complications   
Fall  1  4/24 (16.67%) 
Investigations   
Blood creatinine increased  1  3/24 (12.50%) 
International normalised ratio increased  1  2/24 (8.33%) 
Lymphocyte count decreased  1  2/24 (8.33%) 
Weight decreased  1  2/24 (8.33%) 
Metabolism and nutrition disorders   
Decreased appetite  1  6/24 (25.00%) 
Hypokalaemia  1  3/24 (12.50%) 
Dehydration  1  2/24 (8.33%) 
Hypomagnesaemia  1  2/24 (8.33%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  5/24 (20.83%) 
Pain in extremity  1  5/24 (20.83%) 
Flank pain  1  2/24 (8.33%) 
Musculoskeletal pain  1  2/24 (8.33%) 
Nervous system disorders   
Headache  1  7/24 (29.17%) 
Dizziness  1  5/24 (20.83%) 
Dysarthria  1  3/24 (12.50%) 
Hypoaesthesia  1  3/24 (12.50%) 
Memory impairment  1  2/24 (8.33%) 
Psychiatric disorders   
Confusional state  1  4/24 (16.67%) 
Insomnia  1  4/24 (16.67%) 
Agitation  1  2/24 (8.33%) 
Anxiety  1  2/24 (8.33%) 
Depression  1  2/24 (8.33%) 
Renal and urinary disorders   
Micturition urgency  1  2/24 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  4/24 (16.67%) 
Upper-airway cough syndrome  1  3/24 (12.50%) 
Cough  1  2/24 (8.33%) 
Nasal congestion  1  2/24 (8.33%) 
Oropharyngeal pain  1  2/24 (8.33%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  8/24 (33.33%) 
Palmar-plantar erythrodysaesthesia syndrome  1  3/24 (12.50%) 
Pruritus  1  3/24 (12.50%) 
Decubitus ulcer  1  2/24 (8.33%) 
Rash  1  2/24 (8.33%) 
Rash maculo-papular  1  2/24 (8.33%) 
Skin hyperpigmentation  1  2/24 (8.33%) 
Vascular disorders   
Hypertension  1  2/24 (8.33%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02259010     History of Changes
Other Study ID Numbers: C14020
U1111-1161-5039 ( Registry Identifier: WHO )
First Submitted: October 3, 2014
First Posted: October 8, 2014
Results First Submitted: April 9, 2018
Results First Posted: September 20, 2019
Last Update Posted: September 20, 2019