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Trial record 19 of 59 for:    MLN8237

Phase 2 Study of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02038647
Recruitment Status : Completed
First Posted : January 16, 2014
Results First Posted : December 27, 2018
Last Update Posted : December 27, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Small Cell Lung Cancer
Interventions Drug: Alisertib
Drug: Placebo
Drug: Paclitaxel
Enrollment 178
Recruitment Details Participants took part in the study at 54 investigative sites in the United States, Canada, European Union (Belgium, Czech Republic, France, Germany, Hungary, Italy, Poland and Spain) from 12 May 2014 to 10 July 2017. Data cutoff for the primary analysis was 3 January 2016.
Pre-assignment Details Participants with a diagnosis of Small Cell Lung Cancer (SCLC) were enrolled in 1 of 2 treatment groups: alisertib + paclitaxel or placebo + paclitaxel arm group.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles). Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Period Title: Overall Study
Started 89 89
Completed 0 0
Not Completed 89 89
Reason Not Completed
Progressive Disease             50             59
Adverse Event             18             10
Symptomatic Deterioration             7             7
Withdrawal by Subject             5             2
Not Reported             0             1
Ongoing at Datacut             9             10
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel Total
Hide Arm/Group Description Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles). Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles). Total of all reporting groups
Overall Number of Baseline Participants 89 89 178
Hide Baseline Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment, whether or not any treatment was administered.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 89 participants 89 participants 178 participants
61.8  (8.55) 63.4  (8.56) 62.6  (8.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 89 participants 178 participants
Female
38
  42.7%
39
  43.8%
77
  43.3%
Male
51
  57.3%
50
  56.2%
101
  56.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 89 participants 89 participants 178 participants
2 3 5
Not Hispanic or Latino Number Analyzed 89 participants 89 participants 178 participants
81 84 165
Unknown or Not Reported Number Analyzed 89 participants 89 participants 178 participants
6 1 7
Missing Number Analyzed 89 participants 89 participants 178 participants
0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 89 participants 89 participants 178 participants
83 83 166
Black or African American Number Analyzed 89 participants 89 participants 178 participants
3 2 5
Not reported Number Analyzed 89 participants 89 participants 178 participants
2 2 4
Asian Number Analyzed 89 participants 89 participants 178 participants
1 0 1
Other Number Analyzed 89 participants 89 participants 178 participants
0 1 1
Missing Number Analyzed 89 participants 89 participants 178 participants
0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Belgium Number Analyzed 89 participants 89 participants 178 participants
8 8 16
Czech Republic Number Analyzed 89 participants 89 participants 178 participants
6 5 11
France Number Analyzed 89 participants 89 participants 178 participants
7 5 12
Germany Number Analyzed 89 participants 89 participants 178 participants
2 1 3
Hungary Number Analyzed 89 participants 89 participants 178 participants
16 15 31
Italy Number Analyzed 89 participants 89 participants 178 participants
2 0 2
Poland Number Analyzed 89 participants 89 participants 178 participants
1 3 4
Spain Number Analyzed 89 participants 89 participants 178 participants
6 11 17
Canada Number Analyzed 89 participants 89 participants 178 participants
6 6 12
United States Number Analyzed 89 participants 89 participants 178 participants
35 35 70
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 86 participants 87 participants 173 participants
169.5  (10.43) 168.8  (9.52) 169.2  (9.96)
[1]
Measure Analysis Population Description: Height data is available for n=86,87 participants respectively.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 89 participants 89 participants 178 participants
78.47  (20.561) 75.26  (17.602) 76.87  (19.153)
Body Surface Area   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 86 participants 87 participants 173 participants
1.911  (0.2829) 1.872  (0.2433) 1.891  (0.2637)
[1]
Measure Description: Body surface area=square root of (height [cm]*weight [kg]/3600).
[2]
Measure Analysis Population Description: Body Surface Area data is available for n=86,87 participants respectively.
1.Primary Outcome
Title Progression-Free Survival (PFS) as Determined by Investigator, Analyzed Using FDA Guidelines
Hide Description PFS is defined as time in days from start of study treatment to first documentation of objective tumor progression based on Investigator's assessment or up to death due to any cause, whichever occurs first based on Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Progressive disease (PD) was defined as ≥20% increase in sum longest diameter (LD) in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame Every cycle for first 6 months and then every 2 months until disease progression or death or up to data cut-off: 03 January 2016 (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants who were randomized to study treatment. For participants who have not progressed and is last known to be alive, PFS was censored at the last response assessment that is stable disease (SD) or better as determined by Investigator, and analyzed using FDA Guidelines.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Median (95% Confidence Interval)
Unit of Measure: days
101
(80 to 113)
66
(53 to 83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.113
Comments P-value tests the hypothesis of equal event times in both treatment arms obtained using the Log-rank test stratified by disease subtype as sensitive versus resistant/refractory and the presence of brain metastases.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.557 to 1.067
Estimation Comments The stratification factors were: disease subtype as sensitive versus resistant/refractory and the presence of brain metastases (yes or no) with treatment (Alisertib + Paclitaxel vs Placebo + Paclitaxel) as a factor in the model.
2.Secondary Outcome
Title Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with treatment. An AE can be any unfavorable and unintended sign (eg, clinically significant abnormal laboratory finding), symptom, or disease temporally associated with use of drug, whether or not it is considered related to drug. A treatment-emergent adverse event (TEAE) is defined as an AE with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) is any experience that suggests 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 congenital anomaly/birth defect or is medically significant per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Time Frame From the first dose through 30 days after the last dose of study medication: data cut-off 03 January 2016 (Up to 10.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all participants who received at least 1 dose of any study drug.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 87 89
Measure Type: Number
Unit of Measure: percentage of participants
TEAEs 99 96
SAEs 44 31
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time in days from the date of randomization to the date of death due to any cause.
Time Frame Contact every 2 months after EOT/disease progression until the sooner of death, study closure, or 14 months after the last participant was randomized up to data cut-off: 3 January 2016 (approximately 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Median (95% Confidence Interval)
Unit of Measure: days
186
(150 to 219)
165
(128 to 183)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.714
Comments P-value tests the hypothesis of equal event times in both treatment arms obtained using the Log-rank test stratified by disease subtype as sensitive versus resistant/refractory and the presence of brain metastases.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.652 to 1.341
Estimation Comments The stratification factors were: disease subtype as sensitive versus resistant/refractory and the presence of brain metastases (yes or no) with treatment (Alisertib + Paclitaxel vs Placebo + Paclitaxel) as a factor in the model.
4.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR is defined as the percentage of participants who achieved CR or partial response (PR) as best response based on Investigator's assessment according to RECIST v 1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as ≥ 30% decrease in sum of LD of target lesions in reference to Baseline sum LD.
Time Frame Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22
(14 to 33)
18
(11 to 28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.406
Comments Stratification factors were disease subtypes (sensitive versus resistant/refractory), the presence of brain metastases and region.
Method Weighted Cochran-Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.35 to 1.55
Estimation Comments Logistic regression using ORR as dependent variable, treatment arm as independent variable and disease subtype (sensitive vs resistant/refractory) and presence of brain metastases as stratification factors.
5.Secondary Outcome
Title Complete Response Rate (CRR)
Hide Description CRR is defined as the percentage of participants who achieved CR as best response and based on Investigator's assessment according to RECIST v 1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
Time Frame Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1
(1 to 6)
0
(0 to 0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.283
Comments Stratification factors were disease subtypes (sensitive versus resistant/refractory), the presence of brain metastases and region.
Method Weighted Cochran-Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
0.01 to 9999.99
Estimation Comments Logistic regression using CRR as dependent variable, treatment arm as independent variable and disease subtype (sensitive vs resistant/refractory) and presence of brain metastases as stratification factors.
6.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was defined as the percentage of participants who achieved CR, PR, or SD (when SD was a minimum of 8 weeks in duration). Duration of SD was defined as the time from the date of randomization to the date of first documentation of disease progression for participants who achieved SD as their best overall response. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as ≥ 30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame Baseline until disease progression, death or EOT up to data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58
(47 to 69)
46
(35 to 57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib + Paclitaxel, Placebo + Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments Stratification factors were disease subtypes (sensitive versus resistant/refractory), the presence of brain metastases and region.
Method Weighted Cochran-Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.32 to 1.08
Estimation Comments Logistic regression using DCR as dependent variable, treatment arm as independent variable and disease subtype (sensitive vs resistant/refractory) and presence of brain metastases as stratification factors.
7.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders. PR was defined as ≥ 30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame From first documented response until disease progression until data cut-off 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment. Responders were evaluated for this outcome measure. Responders without documentation of PD were censored at their date of last response assessment that was SD or better.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 20 16
Median (95% Confidence Interval)
Unit of Measure: days
96
(84 to 141)
85
(58 to 177)
8.Secondary Outcome
Title Change From Baseline in Symptom (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) Score at Cycle 5
Hide Description European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is 30-item questionnaire with 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (fatigue, nausea, vomiting and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions use 7-point scale (1=very poor – 7=Excellent). Total Score=0-100 scale; for 5 functional scales and global quality-of-life scale, a higher score=a better level of functioning. For symptoms scale, higher score= higher level of symptoms. EORTC QLQ-LC13 is considered as standard instrument to assess the quality of life (QL) of lung cancer participants. Total Score=0-100. Higher score=increase in level of symptomatology. The change between (QLQ-LC13 Cough Scale, QLQ-C30 Dyspnea Scale, QLQ-C30 Pain Scale) score collected at Cycle 5 relative to baseline.
Time Frame Baseline up to Cycle 5 (approximately 4.6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment. Here number of participants analyzed are participants evaluated in this outcome measure at the specific timepoint.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 20 15
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change at Cycle 5, QLQ-LC-13 Cough Scale -10.94  (3.07) 8.07  (6.04)
Change at Cycle 5, QLQ-C30 Dyspnea Scale -3.48  (4.25) -1.09  (2.92)
Change at Cycle 5, QLQ-C30 Pain Scale -4.82  (4.86) -4.88  (5.16)
9.Secondary Outcome
Title Percentage of Participants Experiencing Symptom Relief
Hide Description Percentage of participants experiencing symptom relief, including coughing relief, dyspnea relief, and pain relief. Coughing relief is defined as a decrease from baseline ≥ 10 in QLQ-LC13 cough scale/item score. Dyspnea relief is defined as a decrease from baseline ≥ 10 in QLQ-C30 dyspnea scale/item score. Pain relief is defined as a decrease from baseline ≥ 10 in QLQ-C30 pain scale score. EORTC QLQ-C30 is 30-item questionnaire with 5 functional scales, 1 global health status scale, 3 symptom scales, 6 single items. Total Score=0-100 scale; for 5 functional scales and global quality-of-life scale, a higher score=a better level of functioning. For symptoms scale, higher score= higher level of symptoms. EORTC QLQ-LC13 is considered as standard instrument to assess the QL of lung cancer participants. Total Score=0-100. Higher score=increase in level of symptomatology.
Time Frame Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment. Participants without coughing/dyspnea/pain relief were censored at their last assessment.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Coughing Relief
28
(19 to 39)
24
(15 to 34)
Dyspnea Relief
31
(22 to 42)
16
(9 to 25)
Pain Relief
39
(29 to 50)
36
(26 to 47)
10.Secondary Outcome
Title Time to Symptom Relief
Hide Description Time to symptom (coughing/dyspnea/pain) relief was defined as the time from the date of randomization to the date of first detection of coughing/dyspnea/pain relief, respectively.
Time Frame Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment. Participants without coughing/dyspnea/pain relief were censored at their last assessment.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Median (95% Confidence Interval)
Unit of Measure: months
Time to Coughing Relief
NA [1] 
(7.6 to NA)
NA [2] 
(NA to NA)
Time to Dyspnea Relief
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
Time to Pain Relief
3.0 [3] 
(1.9 to NA)
3.7 [3] 
(1.1 to NA)
[1]
Median and Upper Limit of Confidence Interval (CI) were not estimable due to low number of participants with events.
[2]
Median, Lower and Upper Limit of CI were not estimable due to low number of participants with events.
[3]
Upper Limit of CI was not reached due to low number of participants with events.
11.Secondary Outcome
Title Time to Symptom Progression
Hide Description Time to coughing/dyspnea/pain progression was defined as time from the date of randomization to date of first detection of progression. Coughing progression was defined as increase from baseline ≥10 in QLQ-LC13 cough scale/item score. Dyspnea progression was defined as increase from baseline ≥10 in QLQ-C30 dyspnea scale/item score. Pain progression was defined as increase from baseline ≥10 in QLQ-C30 pain scale score. EORTC QLQ-C30 is 30-item questionnaire with 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (fatigue, nausea, vomiting and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-LC13 is 13-item scale for assessing treatment-specific symptoms in lung cancer. Total Score= 0-100 scale; for 5 functional scales and global quality-of-life scale, higher score=better level of functioning. For symptoms scale, higher score=higher level of symptoms.
Time Frame Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study treatment. Participant without coughing/dyspnea/pain progression were censored at their last assessment.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 89 89
Median (95% Confidence Interval)
Unit of Measure: months
Time to Coughing Progression
NA [1] 
(NA to NA)
2.8
(2.2 to 6.3)
Time to Dyspnea Progression
3.7 [2] 
(1.9 to NA)
4.6
(1.9 to 6.3)
Time to Pain Progression
2.9 [2] 
(2.1 to NA)
2.8 [2] 
(1.9 to NA)
[1]
Median, Lower and Upper Limit of CI were not estimable due to low number of participants with events.
[2]
Upper Limit of CI was not estimable due to low number of participants with events.
12.Secondary Outcome
Title Observed Plasma Concentration for Alisertib
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours (hrs) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of any study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title Alisertib + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Overall Number of Participants Analyzed 87
Mean (Standard Deviation)
Unit of Measure: nM
Cycle 1, Day 1, Pre-Dose Number Analyzed 87 participants
0  (0)
Cycle 1, Day 1, 1 hr Post-Dose Number Analyzed 85 participants
495.37  (663.456)
Cycle 1, Day 1, 2-4 hrs Post-Dose Number Analyzed 85 participants
861.18  (616.951)
Cycle 1, Day 1, 3-6 hrs Post-Dose Number Analyzed 84 participants
1048.88  (716.447)
Cycle 1, Day 1, 10-11 hrs Post-Dose Number Analyzed 12 participants
539.15  (291.170)
Cycle 1, Day 8, 2 hrs Post-Dose Number Analyzed 76 participants
897.41  (816.387)
Cycle 1, Day 15, 6-9 hrs Post-Dose (1st Sample) Number Analyzed 53 participants
1102.93  (612.265)
Cycle 1, Day 15, 6-9 hrs Post-Dose (2nd Sample) Number Analyzed 51 participants
976.92  (572.090)
13.Secondary Outcome
Title Observed Plasma Concentration for Paclitaxel
Hide Description [Not Specified]
Time Frame Day 1 pre-dose and 1, 2-4, 3-6, 10-11 hours post-dose; Day 8, 2 hours post-dose; Day 15, 6-9 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Due to change in planned analysis, data was only collected and summarized for alisertib not for paclitaxel.
Arm/Group Title Alisertib + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Other Pre-specified Outcome
Title Biomarker Correlative Studies Including Circulating Tumor Cells and Circulating DNA Assessments
Hide Description [Not Specified]
Time Frame Day 1 cycle 1 in a 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
This is an exploratory endpoint.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Other Pre-specified Outcome
Title Health Related Quality of Life (HRQOL )
Hide Description [Not Specified]
Time Frame Baseline up to Cycle 11, data cut-off: 03 January 2016 (approximately 9.8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This is an exploratory endpoint.
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description:
Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles).
Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame First dose of study drug through 30 days after the last dose of study drug (Up to 646 Days)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population included all participants who received at least dose of any study drug.
 
Arm/Group Title Alisertib + Paclitaxel Placebo + Paclitaxel
Hide Arm/Group Description Alisertib 40 mg, tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 60 mg/m^2 intravenously (IV) once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 17 Cycles). Alisertib placebo-matching tablets, orally, twice a day, 3 days on/4 days off for 3 weeks on Days 1-3, 8-10, and 15-17 in a 28-day cycle along with paclitaxel 80 mg/m^2 IV once a week for 3 weeks on Days 1, 8, and 15 in a 28-day cycle until disease progression (Up to 22 Cycles).
All-Cause Mortality
Alisertib + Paclitaxel Placebo + Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   12/87 (13.79%)      11/89 (12.36%)    
Show Serious Adverse Events Hide Serious Adverse Events
Alisertib + Paclitaxel Placebo + Paclitaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/87 (44.83%)      30/89 (33.71%)    
Blood and lymphatic system disorders     
Febrile neutropenia  1 [1]  9/87 (10.34%)  12 0/89 (0.00%)  0
Neutropenia  1  5/87 (5.75%)  5 0/89 (0.00%)  0
Anaemia  1 [2]  2/87 (2.30%)  2 1/89 (1.12%)  1
Leukopenia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Pancytopenia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Cardiac disorders     
Cardiac failure  1  1/87 (1.15%)  1 1/89 (1.12%)  1
Acute coronary syndrome  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Angina pectoris  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Pericardial effusion  1  0/87 (0.00%)  0 2/89 (2.25%)  2
Gastrointestinal disorders     
Diarrhoea  1  5/87 (5.75%)  5 0/89 (0.00%)  0
Stomatitis  1  4/87 (4.60%)  5 1/89 (1.12%)  1
Abdominal pain  1  1/87 (1.15%)  1 1/89 (1.12%)  1
Vomiting  1  0/87 (0.00%)  0 2/89 (2.25%)  2
Constipation  1  1/87 (1.15%)  1 0/89 (0.00%)  0
General disorders     
General physical health deterioration  1 [3]  3/87 (3.45%)  4 1/89 (1.12%)  1
Fatigue  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Pyrexia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Systemic inflammatory response syndrome  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Hepatobiliary disorders     
Bile duct stenosis  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Infections and infestations     
Neutropenic sepsis  1 [1]  2/87 (2.30%)  3 0/89 (0.00%)  0
Bacteraemia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Sepsis  1 [1]  1/87 (1.15%)  1 0/89 (0.00%)  0
Septic shock  1 [1]  1/87 (1.15%)  1 0/89 (0.00%)  0
Pneumonia  1 [2]  3/87 (3.45%)  3 1/89 (1.12%)  3
Pneumocystis jirovecii infection  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Pneumocystis jirovecii pneumonia  1 [2]  0/87 (0.00%)  0 1/89 (1.12%)  2
Fungal infection  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Oral herpes  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Respiratory tract infection  1  1/87 (1.15%)  1 1/89 (1.12%)  1
Influenza  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Erysipelas  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Injury, poisoning and procedural complications     
Fall  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Metabolism and nutrition disorders     
Dehydration  1 [2]  1/87 (1.15%)  1 2/89 (2.25%)  2
Diabetic metabolic decompensation  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Hypokalaemia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Hyponatraemia  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/87 (1.15%)  1 2/89 (2.25%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Small cell lung cancer  1 [4]  0/87 (0.00%)  0 6/89 (6.74%)  7
Metastases to meninges  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Metastases to peritoneum  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Lung neoplasm malignant  1 [5]  2/87 (2.30%)  3 0/89 (0.00%)  0
Glioblastoma  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Tumour pain  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Metastases to liver  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Nervous system disorders     
Epilepsy  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Seizure  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Ataxia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Cognitive disorder  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Neuropathy peripheral  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Paraplegia  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Psychiatric disorders     
Confusional state  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Mental status changes  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1 [6]  3/87 (3.45%)  3 0/89 (0.00%)  0
Acute respiratory failure  1 [2]  1/87 (1.15%)  2 1/89 (1.12%)  1
Pulmonary embolism  1 [2]  2/87 (2.30%)  2 1/89 (1.12%)  1
Dyspnoea  1  1/87 (1.15%)  1 0/89 (0.00%)  0
Hypoxia  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Haemoptysis  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Pneumonitis  1  0/87 (0.00%)  0 1/89 (1.12%)  1
Pulmonary oedema  1 [7]  1/87 (1.15%)  2 0/89 (0.00%)  0
Vascular disorders     
Aortic thrombosis  1 [7]  1/87 (1.15%)  2 0/89 (0.00%)  0
Embolism  1  1/87 (1.15%)  1 0/89 (0.00%)  0
1
Term from vocabulary, MedDRA Version 15.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group and is related with study drug.
[2]
One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and is not related with study drug.
[3]
One treatment-emergent death occurred during treatment in Placebo + Paclitaxel arm group and two treatment-emergent deaths occurred during treatment in Alisertib + Paclitaxel arm group and are not related with study drug.
[4]
Four treatment-emergent deaths occurred during treatment in Placebo + Paclitaxel arm group and are not related with study drug.
[5]
Two treatment-emergent deaths occurred during treatment in Alisertib+ Paclitaxel arm group and are not related with study drug.
[6]
Two treatment-emergent death occurred during treatment in Alisertib+ Paclitaxel arm group and is not related with study drug.
[7]
One treatment-emergent death occurred during treatment in Alisertib + Paclitaxel arm group 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%
Alisertib + Paclitaxel Placebo + Paclitaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   85/87 (97.70%)      80/89 (89.89%)    
Blood and lymphatic system disorders     
Anaemia  1  38/87 (43.68%)  55 18/89 (20.22%)  23
Neutropenia  1  41/87 (47.13%)  89 7/89 (7.87%)  11
Leukopenia  1  12/87 (13.79%)  18 5/89 (5.62%)  8
Thrombocytopenia  1  7/87 (8.05%)  7 3/89 (3.37%)  3
Gastrointestinal disorders     
Diarrhoea  1  48/87 (55.17%)  104 18/89 (20.22%)  32
Nausea  1  30/87 (34.48%)  43 30/89 (33.71%)  38
Vomiting  1  28/87 (32.18%)  45 19/89 (21.35%)  27
Stomatitis  1  27/87 (31.03%)  49 6/89 (6.74%)  7
Constipation  1  8/87 (9.20%)  11 21/89 (23.60%)  25
Abdominal pain  1  12/87 (13.79%)  13 3/89 (3.37%)  4
Abdominal pain upper  1  7/87 (8.05%)  9 6/89 (6.74%)  6
Dyspepsia  1  8/87 (9.20%)  9 4/89 (4.49%)  4
Gastrooesophageal reflux disease  1  5/87 (5.75%)  7 5/89 (5.62%)  5
Dysphagia  1  5/87 (5.75%)  5 3/89 (3.37%)  3
General disorders     
Fatigue  1  38/87 (43.68%)  52 28/89 (31.46%)  35
Asthenia  1  14/87 (16.09%)  32 11/89 (12.36%)  16
Oedema peripheral  1  6/87 (6.90%)  7 10/89 (11.24%)  14
Pyrexia  1  8/87 (9.20%)  8 6/89 (6.74%)  7
Non-cardiac chest pain  1  4/87 (4.60%)  5 5/89 (5.62%)  5
Infections and infestations     
Upper respiratory tract infection  1  2/87 (2.30%)  2 5/89 (5.62%)  5
Injury, poisoning and procedural complications     
Fall  1  5/87 (5.75%)  5 3/89 (3.37%)  4
Investigations     
Neutrophil count decreased  1  14/87 (16.09%)  28 4/89 (4.49%)  4
Weight decreased  1  13/87 (14.94%)  18 5/89 (5.62%)  7
White blood cell count decreased  1  12/87 (13.79%)  20 1/89 (1.12%)  4
Metabolism and nutrition disorders     
Decreased appetite  1  29/87 (33.33%)  36 19/89 (21.35%)  26
Hypokalaemia  1  10/87 (11.49%)  12 6/89 (6.74%)  7
Dehydration  1  7/87 (8.05%)  8 4/89 (4.49%)  5
Hypomagnesaemia  1  5/87 (5.75%)  5 6/89 (6.74%)  10
Hypocalcaemia  1  7/87 (8.05%)  7 1/89 (1.12%)  1
Hyperglycaemia  1  5/87 (5.75%)  6 1/89 (1.12%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/87 (10.34%)  12 5/89 (5.62%)  10
Muscular weakness  1  6/87 (6.90%)  6 6/89 (6.74%)  11
Back pain  1  5/87 (5.75%)  8 6/89 (6.74%)  9
Musculoskeletal pain  1  4/87 (4.60%)  4 5/89 (5.62%)  5
Pain in extremity  1  3/87 (3.45%)  3 5/89 (5.62%)  7
Musculoskeletal chest pain  1  0/87 (0.00%)  0 6/89 (6.74%)  8
Nervous system disorders     
Dizziness  1  15/87 (17.24%)  17 9/89 (10.11%)  14
Headache  1  9/87 (10.34%)  9 6/89 (6.74%)  7
Neuropathy peripheral  1  8/87 (9.20%)  10 7/89 (7.87%)  10
Paraesthesia  1  4/87 (4.60%)  5 6/89 (6.74%)  9
Hypoaesthesia  1  4/87 (4.60%)  5 5/89 (5.62%)  6
Somnolence  1  5/87 (5.75%)  6 3/89 (3.37%)  3
Dysgeusia  1  2/87 (2.30%)  2 5/89 (5.62%)  5
Psychiatric disorders     
Insomnia  1  7/87 (8.05%)  7 7/89 (7.87%)  8
Confusional state  1  2/87 (2.30%)  2 5/89 (5.62%)  5
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  21/87 (24.14%)  23 19/89 (21.35%)  22
Cough  1  17/87 (19.54%)  19 17/89 (19.10%)  18
Productive cough  1  4/87 (4.60%)  4 9/89 (10.11%)  12
Epistaxis  1  3/87 (3.45%)  3 7/89 (7.87%)  10
Dysphonia  1  5/87 (5.75%)  5 3/89 (3.37%)  3
Skin and subcutaneous tissue disorders     
Alopecia  1  14/87 (16.09%)  15 5/89 (5.62%)  5
Rash maculo-papular  1  0/87 (0.00%)  0 6/89 (6.74%)  10
Vascular disorders     
Hypertension  1  5/87 (5.75%)  5 11/89 (12.36%)  13
1
Term from vocabulary, MedDRA Version 15.0
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
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02038647     History of Changes
Other Study ID Numbers: C14018
2013-003713-18 ( EudraCT Number )
U1111-1154-9805 ( Registry Identifier: WHO )
DRKS00007849 ( Registry Identifier: DRKS )
First Submitted: December 4, 2013
First Posted: January 16, 2014
Results First Submitted: February 21, 2018
Results First Posted: December 27, 2018
Last Update Posted: December 27, 2018