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Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

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ClinicalTrials.gov Identifier: NCT01646021
Recruitment Status : Completed
First Posted : July 20, 2012
Results First Posted : March 1, 2017
Last Update Posted : January 19, 2018
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Mantle Cell Lymphoma
Interventions Drug: Ibrutinib
Drug: Temsirolimus
Enrollment 280
Recruitment Details  
Pre-assignment Details 139 participants were randomized and treated in the ibrutinib arm and 141 participants were randomized to the temsirolimus arm.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle. Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Period Title: Overall Study
Started 139 141
Treated 139 139
Completed 0 0
Not Completed 139 141
Reason Not Completed
Death             77             83
Study Terminated by Sponsor             50             41
Lost to Follow-up             2             2
Withdrawal by Subject             10             15
Arm/Group Title Ibrutinib Temsirolimus Total
Hide Arm/Group Description Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle. Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period. Total of all reporting groups
Overall Number of Baseline Participants 139 141 280
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 139 participants 141 participants 280 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
53
  38.1%
54
  38.3%
107
  38.2%
>=65 years
86
  61.9%
87
  61.7%
173
  61.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 139 participants 141 participants 280 participants
66.7  (8.68) 67.1  (9.83) 66.9  (9.26)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 139 participants 141 participants 280 participants
Female 39 33 72
Male 100 108 208
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 139 participants 141 participants 280 participants
Belgium 7 10 17
Brazil 5 10 15
Canada 6 3 9
Colombia 3 4 7
Czech Republic 7 7 14
Germany 12 11 23
Spain 5 14 19
France 5 5 10
United Kingdom 11 16 27
Hungary 5 7 12
Ireland 2 1 3
Italy 6 8 14
South Korea 11 3 14
Mexico 1 1 2
Netherlands 2 0 2
Poland 9 14 23
Portugal 3 3 6
Russian Federation 18 11 29
Sweden 10 8 18
Taiwan 5 1 6
Ukraine 6 4 10
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to [>=] 50 percent [%] of previously involved sites from nadir).
Time Frame Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Median (95% Confidence Interval)
Unit of Measure: Months
15.6
(10.6 to 25.1)
6.2
(4.2 to 7.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib, Temsirolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.35 to 0.60
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR is defined as the percentage of participants who achieved either CR or PR as best overall response based on the investigator assessment. CR is Disappearance of all target lesions while PR is greater than or equal to 30 % decrease in the sum of the longest diameter of target lesions and Overall Response (OR) is sum of CR and PR.
Time Frame Approximately up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Measure Type: Number
Unit of Measure: Percentage of participants
77.0 46.8
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was defined as the interval between the date of randomization and the date of death from any cause.
Time Frame Approximately up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Median (95% Confidence Interval)
Unit of Measure: Months
30.3
(19.1 to 42.1)
23.5
(13.0 to 30.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ibrutinib, Temsirolimus
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0621
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.54 to 1.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response
Hide Description Duration of response (CR or PR), defined as the duration in days from the date of initial response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. The analysis was based on the investigator assessment.
Time Frame Approximately up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants responded for this outcome measure.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 107 66
Median (95% Confidence Interval)
Unit of Measure: Months
23.1
(16.2 to 28.1)
6.3
(4.7 to 8.6)
5.Secondary Outcome
Title Time-to-Next Treatment
Hide Description Time to next treatment was measured from the date of randomization to the start date of any anti-neoplastic treatment subsequent to study treatment.
Time Frame Approximately up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Median (95% Confidence Interval)
Unit of Measure: Months
31.8 [1] 
(23.3 to NA)
11.6
(8.0 to 13.3)
[1]
upper 95%CI was not estimable due to less than 50% participants had events occurred
6.Secondary Outcome
Title Progression-Free Survival 2
Hide Description Progression-free survival 2 defined as the time interval between the date of randomization and date of event, defined as progressive disease as assessed by investigator that started after the next line of subsequent anti-neoplastic therapy (including cross-over to ibrutinib), death from any cause, or the start of the second subsequent anti-neoplastic therapy if no progressive disease was recorded after the first subsequent anti-neoplastic therapy.
Time Frame Approximately up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Median (95% Confidence Interval)
Unit of Measure: Months
26.2
(17.2 to 32.4)
15.4
(10.2 to 21.3)
7.Secondary Outcome
Title Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)
Hide Description Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life.
Time Frame Approximately up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(81.4 to NA)
10.6
(6.6 to 15.3)
[1]
Here, NA indicates median and upper limit of CI of FACT-Lym was not estimable at final analysis due to less than 50% patients had events occurred.
8.Secondary Outcome
Title Number of Participants Affected With Treatment-emergent Adverse Events
Hide Description An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of the study drug.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 139
Measure Type: Count of Participants
Unit of Measure: Participants
139
 100.0%
138
  99.3%
9.Other Pre-specified Outcome
Title Time to Response
Hide Description Time to response for participants with CR/PR, defined as the interval between the date of randomization and date of initial documentation of response.
Time Frame Approximately up to 2.8 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants responded for this outcome measure.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 100 57
Median (Full Range)
Unit of Measure: Months
2.15
(0.5 to 10.4)
2.14
(0.9 to 12.0)
10.Other Pre-specified Outcome
Title Extent of Exposure of Time
Hide Description Extent of exposure is defined as the duration of the treatment administered during the study. Duration of exposure is calculated as the number of months between the start and end of treatment.
Time Frame Approximately up to 46.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analyses Set (SAS) population includes all the randomized participants who received at least 1 dose of study agent (ibrutinib or temsirolimus) during the treatment phase.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 139
Median (Full Range)
Unit of Measure: Months
14.39
(0.0 to 46.8)
3.02
(0.0 to 31.4)
11.Other Pre-specified Outcome
Title One Year Survival Rate
Hide Description One -year survival rate, defined as the proportion of participants who were alive 1 year after randomization.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of participants
0.68
(0.59 to 0.75)
0.61
(0.52 to 0.69)
12.Other Pre-specified Outcome
Title Area Under the Plasma Concentration of Ibrutinib During Steady State (AUC-ss)
Hide Description The AUC-ss is the area under the plasma concentration time curve observed during steady state.
Time Frame Cycle 1 and 2 (Day 1): Predose, 1, 2, 4 hr. postdose; Cycle 3 (day 1): Predose (Each cycle is of 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set included the participants who had received one dose of study drug had at least 1 pharmacokinetic sample obtained post-treatment.
Arm/Group Title Ibrutinib
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Overall Number of Participants Analyzed 139
Mean (Standard Deviation)
Unit of Measure: nanogram*hour per milliliter (ng*h/mL)
561.6  (448)
13.Other Pre-specified Outcome
Title Number of Participants With Biomarkers That Alter B-cell Receptor (BCR) Signaling or Activate Alternative Signaling Pathways and to Explore Their Association With Response or Resistance to Ibrutinib
Hide Description Biomarker evaluations to identify markers altering BCR signaling or activate alternative signaling pathways and explore their association with response or resistance to ibrutinib. Next-generation sequencing at baseline identifies possible primary resistance mutations and those found only at progression are acquired mutations on therapy.
Time Frame Approximately up to 28.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Measure Type: Number
Unit of Measure: Participants
61 53
14.Other Pre-specified Outcome
Title Number of Hospitalizations Reported Related Medical Resource Utilization Information (MRUI)
Hide Description Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.
Time Frame Approximately up to 28.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants responded for this outcome measure.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 83 91
Mean (Standard Deviation)
Unit of Measure: Hospitalizations
3.1  (4.6) 2.8  (4.3)
15.Other Pre-specified Outcome
Title Number of Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)
Hide Description Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.
Time Frame Approximately up to 28.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants responded for this outcome measure.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: Emergency room visits
1.2  (0.4) 1.2  (0.4)
16.Other Pre-specified Outcome
Title Days of Hospitalization and Emergency Room Visits Reported Related Medical Resource Utilization Information (MRUI)
Hide Description Medical resource utilization data associated with medical encounters related to disease was reported for all participants throughout the study.
Time Frame Approximately up to 28.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 139 141
Mean (Standard Deviation)
Unit of Measure: Days
Mean days of hospitalization Number Analyzed 83 participants 91 participants
19.7  (20.5) 20.3  (22.4)
Mean days of emergency room visits Number Analyzed 5 participants 5 participants
1.8  (1.3) 1.6  (1.3)
17.Other Pre-specified Outcome
Title The Mean Change From Baseline in Euro QoL Five-Dimension (EQ-5D-5L) Scores for Each Post Baseline Assessment
Hide Description The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and possible total score range -0.594 to 1; higher score indicates a better health state.
Time Frame Baseline, Cycle 2, 3, 4, 5, 6, 7, 8, 11, 14, 17, 20, 28, 36 and End of treatment (approximately up to 23 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population included all participants randomized into the study regardless of treatment actually received. The 'N' (number of participants analyzed) signifies the number of participants evaluated for this outcome measure.
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description:
Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle.
Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
Overall Number of Participants Analyzed 138 130
Mean (Standard Deviation)
Unit of Measure: Units on scale
Baseline Number Analyzed 130 participants 120 participants
0.7  (0.2) 0.7  (0.2)
Change at Cycle 2 Number Analyzed 113 participants 95 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 3 Number Analyzed 115 participants 85 participants
0.1  (0.2) -0.1  (0.2)
Change at Cycle 4 Number Analyzed 103 participants 70 participants
0.0  (0.2) 0.0  (0.3)
Change at Cycle 5 Number Analyzed 102 participants 57 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 6 Number Analyzed 99 participants 49 participants
0.1  (0.2) 0.0  (0.2)
Change at Cycle 7 Number Analyzed 98 participants 39 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 8 Number Analyzed 90 participants 37 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 11 Number Analyzed 88 participants 33 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 14 Number Analyzed 72 participants 26 participants
0.0  (0.2) 0.0  (0.1)
Change at Cycle 17 Number Analyzed 69 participants 19 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 20 Number Analyzed 64 participants 16 participants
0.0  (0.2) 0.0  (0.2)
Change at Cycle 28 Number Analyzed 22 participants 6 participants
-0.1  (0.2) 0.1  (0.2)
Change at Cycle 36 Number Analyzed 10 participants 4 participants
0.0  (0.3) -0.1  (0.2)
Change at End of treatment Number Analyzed 23 participants 65 participants
0.0  (0.2) -0.1  (0.3)
Time Frame Approximately up to 4 years
Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose of study agent (ibrutinib or temsirolimus) during the treatment phase.
 
Arm/Group Title Ibrutinib Temsirolimus
Hide Arm/Group Description Participants received 560 milligram (mg) ibrutinib (4*140 mg capsules) by mouth once daily continuous (without interruption) self-administered home treatment during the 21 day cycle. Participants received Temsirolimus intravenous (IV) infusion 175 mg on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each subsequent 21 day cycle. Each temsirolimus dose is infused over a 30 to 60 minute period.
All-Cause Mortality
Ibrutinib Temsirolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   130/139 (93.53%)   137/139 (98.56%) 
Hide Serious Adverse Events
Ibrutinib Temsirolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   79/139 (56.83%)   83/139 (59.71%) 
Blood and lymphatic system disorders     
Anaemia * 1  4/139 (2.88%)  5/139 (3.60%) 
Autoimmune Haemolytic Anaemia * 1  1/139 (0.72%)  0/139 (0.00%) 
Febrile Neutropenia * 1  2/139 (1.44%)  1/139 (0.72%) 
Leukocytosis * 1  2/139 (1.44%)  0/139 (0.00%) 
Lymphocytosis * 1  1/139 (0.72%)  0/139 (0.00%) 
Neutropenia * 1  1/139 (0.72%)  1/139 (0.72%) 
Splenic Infarction * 1  1/139 (0.72%)  0/139 (0.00%) 
Thrombocytopenia * 1  5/139 (3.60%)  3/139 (2.16%) 
Cardiac disorders     
Acute Myocardial Infarction * 1  1/139 (0.72%)  0/139 (0.00%) 
Angina Pectoris * 1  0/139 (0.00%)  1/139 (0.72%) 
Angina Unstable * 1  0/139 (0.00%)  1/139 (0.72%) 
Arteriosclerosis Coronary Artery * 1  1/139 (0.72%)  0/139 (0.00%) 
Atrial Fibrillation * 1  7/139 (5.04%)  2/139 (1.44%) 
Atrial Flutter * 1  1/139 (0.72%)  0/139 (0.00%) 
Bradycardia * 1  1/139 (0.72%)  0/139 (0.00%) 
Cardiac Arrest * 1  0/139 (0.00%)  1/139 (0.72%) 
Cardiac Failure Acute * 1  0/139 (0.00%)  1/139 (0.72%) 
Cardiac Failure Chronic * 1  1/139 (0.72%)  1/139 (0.72%) 
Cardiac Failure Congestive * 1  0/139 (0.00%)  1/139 (0.72%) 
Cardiopulmonary Failure * 1  0/139 (0.00%)  1/139 (0.72%) 
Coronary Artery Insufficiency * 1  1/139 (0.72%)  0/139 (0.00%) 
Coronary Artery Stenosis * 1  0/139 (0.00%)  1/139 (0.72%) 
Myocardial Ischaemia * 1  0/139 (0.00%)  1/139 (0.72%) 
Pericarditis * 1  1/139 (0.72%)  0/139 (0.00%) 
Supraventricular Tachycardia * 1  1/139 (0.72%)  0/139 (0.00%) 
Eye disorders     
Cataract * 1  0/139 (0.00%)  1/139 (0.72%) 
Diabetic Retinopathy * 1  1/139 (0.72%)  0/139 (0.00%) 
Vitreous Haemorrhage * 1  1/139 (0.72%)  0/139 (0.00%) 
Gastrointestinal disorders     
Abdominal Hernia * 1  0/139 (0.00%)  1/139 (0.72%) 
Abdominal Pain * 1  5/139 (3.60%)  1/139 (0.72%) 
Diarrhoea * 1  3/139 (2.16%)  4/139 (2.88%) 
Duodenal Stenosis * 1  1/139 (0.72%)  0/139 (0.00%) 
Dysphagia * 1  1/139 (0.72%)  0/139 (0.00%) 
Enterocolitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Gastric Ulcer * 1  1/139 (0.72%)  0/139 (0.00%) 
Gastritis Haemorrhagic * 1  0/139 (0.00%)  1/139 (0.72%) 
Gastrointestinal Haemorrhage * 1  1/139 (0.72%)  1/139 (0.72%) 
Haemorrhoids * 1  0/139 (0.00%)  1/139 (0.72%) 
Intestinal Haemorrhage * 1  0/139 (0.00%)  1/139 (0.72%) 
Lower Gastrointestinal Haemorrhage * 1  0/139 (0.00%)  1/139 (0.72%) 
Proctitis * 1  1/139 (0.72%)  0/139 (0.00%) 
Small Intestinal Obstruction * 1  1/139 (0.72%)  0/139 (0.00%) 
Stomatitis * 1  0/139 (0.00%)  3/139 (2.16%) 
Vomiting * 1  0/139 (0.00%)  1/139 (0.72%) 
General disorders     
Fatigue * 1  2/139 (1.44%)  3/139 (2.16%) 
General Physical Health Deterioration * 1  3/139 (2.16%)  5/139 (3.60%) 
Malaise * 1  0/139 (0.00%)  1/139 (0.72%) 
Mucosal Inflammation * 1  0/139 (0.00%)  1/139 (0.72%) 
Multi-Organ Failure * 1  4/139 (2.88%)  0/139 (0.00%) 
Oedema * 1  0/139 (0.00%)  1/139 (0.72%) 
Pain * 1  0/139 (0.00%)  1/139 (0.72%) 
Pyrexia * 1  3/139 (2.16%)  7/139 (5.04%) 
Hepatobiliary disorders     
Hepatitis Toxic * 1  1/139 (0.72%)  1/139 (0.72%) 
Immune system disorders     
Hypersensitivity * 1  0/139 (0.00%)  1/139 (0.72%) 
Infections and infestations     
Abscess Limb * 1  1/139 (0.72%)  0/139 (0.00%) 
Atypical Pneumonia * 1  0/139 (0.00%)  1/139 (0.72%) 
Bacteraemia * 1  1/139 (0.72%)  0/139 (0.00%) 
Bronchopulmonary Aspergillosis * 1  0/139 (0.00%)  1/139 (0.72%) 
Cellulitis * 1  1/139 (0.72%)  0/139 (0.00%) 
Clostridium Difficile Colitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Cystitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Device Related Infection * 1  1/139 (0.72%)  2/139 (1.44%) 
Diverticulitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Erysipelas * 1  1/139 (0.72%)  0/139 (0.00%) 
Gastroenteritis * 1  1/139 (0.72%)  2/139 (1.44%) 
Hepatitis B * 1  1/139 (0.72%)  0/139 (0.00%) 
Herpes Zoster * 1  0/139 (0.00%)  1/139 (0.72%) 
Infection * 1  1/139 (0.72%)  2/139 (1.44%) 
Infectious Colitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Laryngitis * 1  1/139 (0.72%)  0/139 (0.00%) 
Laryngitis Fungal * 1  0/139 (0.00%)  1/139 (0.72%) 
Liver Abscess * 1  0/139 (0.00%)  1/139 (0.72%) 
Lower Respiratory Tract Infection * 1  2/139 (1.44%)  1/139 (0.72%) 
Lung Infection * 1  2/139 (1.44%)  2/139 (1.44%) 
Neutropenic Sepsis * 1  0/139 (0.00%)  1/139 (0.72%) 
Oral Candidiasis * 1  0/139 (0.00%)  1/139 (0.72%) 
Pharyngitis * 1  1/139 (0.72%)  0/139 (0.00%) 
Pneumocystis Jirovecii Infection * 1  0/139 (0.00%)  1/139 (0.72%) 
Pneumocystis Jirovecii Pneumonia * 1  1/139 (0.72%)  1/139 (0.72%) 
Pneumonia * 1  16/139 (11.51%)  12/139 (8.63%) 
Pneumonia Escherichia * 1  0/139 (0.00%)  1/139 (0.72%) 
Pulmonary Tuberculosis * 1  1/139 (0.72%)  0/139 (0.00%) 
Pyelonephritis * 1  1/139 (0.72%)  0/139 (0.00%) 
Respiratory Tract Infection * 1  0/139 (0.00%)  1/139 (0.72%) 
Sepsis * 1  6/139 (4.32%)  5/139 (3.60%) 
Septic Shock * 1  2/139 (1.44%)  1/139 (0.72%) 
Sinusitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Sinusitis Aspergillus * 1  0/139 (0.00%)  1/139 (0.72%) 
Skin Infection * 1  2/139 (1.44%)  1/139 (0.72%) 
Soft Tissue Infection * 1  1/139 (0.72%)  0/139 (0.00%) 
Tooth Infection * 1  0/139 (0.00%)  1/139 (0.72%) 
Tracheitis * 1  1/139 (0.72%)  0/139 (0.00%) 
Upper Respiratory Tract Infection * 1  0/139 (0.00%)  2/139 (1.44%) 
Urinary Tract Infection * 1  1/139 (0.72%)  3/139 (2.16%) 
Urinary Tract Infection Bacterial * 1  1/139 (0.72%)  0/139 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  1/139 (0.72%)  0/139 (0.00%) 
Fibula Fracture * 1  0/139 (0.00%)  1/139 (0.72%) 
Foreign Body * 1  0/139 (0.00%)  1/139 (0.72%) 
Lumbar Vertebral Fracture * 1  1/139 (0.72%)  0/139 (0.00%) 
Post Procedural Haemorrhage * 1  2/139 (1.44%)  1/139 (0.72%) 
Post Procedural Swelling * 1  1/139 (0.72%)  0/139 (0.00%) 
Rib Fracture * 1  1/139 (0.72%)  0/139 (0.00%) 
Splenic Rupture * 1  2/139 (1.44%)  1/139 (0.72%) 
Subdural Haematoma * 1  1/139 (0.72%)  0/139 (0.00%) 
Toxicity to Various Agents * 1  0/139 (0.00%)  1/139 (0.72%) 
Wound * 1  0/139 (0.00%)  1/139 (0.72%) 
Investigations     
Blood Creatinine Increased * 1  1/139 (0.72%)  0/139 (0.00%) 
Haemoglobin Decreased * 1  1/139 (0.72%)  0/139 (0.00%) 
Neutrophil Count Decreased * 1  1/139 (0.72%)  0/139 (0.00%) 
Platelet Count Decreased * 1  2/139 (1.44%)  0/139 (0.00%) 
Metabolism and nutrition disorders     
Cachexia * 1  1/139 (0.72%)  0/139 (0.00%) 
Decreased Appetite * 1  0/139 (0.00%)  2/139 (1.44%) 
Dehydration * 1  2/139 (1.44%)  1/139 (0.72%) 
Diabetes Mellitus * 1  0/139 (0.00%)  1/139 (0.72%) 
Diabetic Ketoacidosis * 1  1/139 (0.72%)  0/139 (0.00%) 
Hypokalaemia * 1  0/139 (0.00%)  1/139 (0.72%) 
Hyponatraemia * 1  0/139 (0.00%)  1/139 (0.72%) 
Tumour Lysis Syndrome * 1  1/139 (0.72%)  3/139 (2.16%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  1/139 (0.72%)  1/139 (0.72%) 
Bone Pain * 1  0/139 (0.00%)  1/139 (0.72%) 
Chondrocalcinosis Pyrophosphate * 1  1/139 (0.72%)  0/139 (0.00%) 
Intervertebral Disc Compression * 1  0/139 (0.00%)  1/139 (0.72%) 
Osteoarthritis * 1  1/139 (0.72%)  0/139 (0.00%) 
Osteonecrosis * 1  1/139 (0.72%)  0/139 (0.00%) 
Pain in Extremity * 1  1/139 (0.72%)  1/139 (0.72%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma Gastric * 1  0/139 (0.00%)  1/139 (0.72%) 
Basal Cell Carcinoma * 1  1/139 (0.72%)  0/139 (0.00%) 
Bladder Transitional Cell Carcinoma * 1  2/139 (1.44%)  0/139 (0.00%) 
Laryngeal Cancer Metastatic * 1  1/139 (0.72%)  0/139 (0.00%) 
Prostate Cancer * 1  1/139 (0.72%)  0/139 (0.00%) 
Salivary Gland Cancer * 1  1/139 (0.72%)  0/139 (0.00%) 
Squamous Cell Carcinoma * 1  1/139 (0.72%)  0/139 (0.00%) 
Thymoma * 1  1/139 (0.72%)  0/139 (0.00%) 
Transitional Cell Carcinoma * 1  1/139 (0.72%)  0/139 (0.00%) 
Nervous system disorders     
Ataxia * 1  0/139 (0.00%)  1/139 (0.72%) 
Cerebral Ischaemia * 1  0/139 (0.00%)  1/139 (0.72%) 
Cerebrovascular Accident * 1  0/139 (0.00%)  1/139 (0.72%) 
Cognitive Disorder * 1  1/139 (0.72%)  0/139 (0.00%) 
Dysarthria * 1  2/139 (1.44%)  0/139 (0.00%) 
Epilepsy * 1  1/139 (0.72%)  0/139 (0.00%) 
Facial Paresis * 1  1/139 (0.72%)  0/139 (0.00%) 
Headache * 1  1/139 (0.72%)  0/139 (0.00%) 
Ischaemic Stroke * 1  0/139 (0.00%)  1/139 (0.72%) 
Memory Impairment * 1  1/139 (0.72%)  0/139 (0.00%) 
Myoclonus * 1  1/139 (0.72%)  0/139 (0.00%) 
Neuralgia * 1  0/139 (0.00%)  2/139 (1.44%) 
Syncope * 1  1/139 (0.72%)  0/139 (0.00%) 
Transient Ischaemic Attack * 1  1/139 (0.72%)  0/139 (0.00%) 
Tremor * 1  0/139 (0.00%)  1/139 (0.72%) 
Psychiatric disorders     
Confusional State * 1  1/139 (0.72%)  2/139 (1.44%) 
Mental Disorder * 1  1/139 (0.72%)  0/139 (0.00%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  2/139 (1.44%)  1/139 (0.72%) 
Cystitis Haemorrhagic * 1  1/139 (0.72%)  0/139 (0.00%) 
Haematuria * 1  1/139 (0.72%)  0/139 (0.00%) 
Hydronephrosis * 1  1/139 (0.72%)  0/139 (0.00%) 
Nephrotic Syndrome * 1  1/139 (0.72%)  0/139 (0.00%) 
Renal Failure * 1  3/139 (2.16%)  4/139 (2.88%) 
Renal Impairment * 1  0/139 (0.00%)  1/139 (0.72%) 
Reproductive system and breast disorders     
Pelvic Pain * 1  1/139 (0.72%)  0/139 (0.00%) 
Prostatitis * 1  0/139 (0.00%)  1/139 (0.72%) 
Respiratory, thoracic and mediastinal disorders     
Chronic Obstructive Pulmonary Disease * 1  2/139 (1.44%)  0/139 (0.00%) 
Cough * 1  1/139 (0.72%)  0/139 (0.00%) 
Dyspnoea * 1  6/139 (4.32%)  5/139 (3.60%) 
Epistaxis * 1  2/139 (1.44%)  2/139 (1.44%) 
Hypoxia * 1  1/139 (0.72%)  0/139 (0.00%) 
Interstitial Lung Disease * 1  0/139 (0.00%)  2/139 (1.44%) 
Lung Disorder * 1  0/139 (0.00%)  1/139 (0.72%) 
Lung Infiltration * 1  1/139 (0.72%)  0/139 (0.00%) 
Pleural Effusion * 1  6/139 (4.32%)  0/139 (0.00%) 
Pneumonitis * 1  0/139 (0.00%)  3/139 (2.16%) 
Pneumothorax * 1  2/139 (1.44%)  0/139 (0.00%) 
Pulmonary Embolism * 1  1/139 (0.72%)  1/139 (0.72%) 
Pulmonary Oedema * 1  1/139 (0.72%)  1/139 (0.72%) 
Respiratory Failure * 1  2/139 (1.44%)  1/139 (0.72%) 
Skin and subcutaneous tissue disorders     
Guttate Psoriasis * 1  1/139 (0.72%)  0/139 (0.00%) 
Panniculitis * 1  1/139 (0.72%)  0/139 (0.00%) 
Skin Ulcer * 1  0/139 (0.00%)  1/139 (0.72%) 
Vascular disorders     
Deep Vein Thrombosis * 1  0/139 (0.00%)  1/139 (0.72%) 
Haemorrhage * 1  2/139 (1.44%)  0/139 (0.00%) 
Orthostatic Hypotension * 1  1/139 (0.72%)  0/139 (0.00%) 
1
Term from vocabulary, MedDRA Version 18.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ibrutinib Temsirolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   130/139 (93.53%)   137/139 (98.56%) 
Blood and lymphatic system disorders     
Anaemia * 1  27/139 (19.42%)  57/139 (41.01%) 
Neutropenia * 1  21/139 (15.11%)  36/139 (25.90%) 
Thrombocytopenia * 1  25/139 (17.99%)  77/139 (55.40%) 
Cardiac disorders     
Atrial Fibrillation * 1  8/139 (5.76%)  1/139 (0.72%) 
Eye disorders     
Cataract * 1  2/139 (1.44%)  7/139 (5.04%) 
Gastrointestinal disorders     
Abdominal Pain * 1  8/139 (5.76%)  11/139 (7.91%) 
Abdominal Pain Upper * 1  8/139 (5.76%)  3/139 (2.16%) 
Constipation * 1  13/139 (9.35%)  21/139 (15.11%) 
Diarrhoea * 1  45/139 (32.37%)  42/139 (30.22%) 
Dyspepsia * 1  9/139 (6.47%)  1/139 (0.72%) 
Mouth Ulceration * 1  0/139 (0.00%)  8/139 (5.76%) 
Nausea * 1  20/139 (14.39%)  30/139 (21.58%) 
Oral Pain * 1  1/139 (0.72%)  9/139 (6.47%) 
Stomatitis * 1  4/139 (2.88%)  28/139 (20.14%) 
Vomiting * 1  17/139 (12.23%)  9/139 (6.47%) 
General disorders     
Asthenia * 1  12/139 (8.63%)  26/139 (18.71%) 
Fatigue * 1  31/139 (22.30%)  40/139 (28.78%) 
Mucosal Inflammation * 1  2/139 (1.44%)  21/139 (15.11%) 
Oedema Peripheral * 1  19/139 (13.67%)  33/139 (23.74%) 
Pyrexia * 1  24/139 (17.27%)  26/139 (18.71%) 
Infections and infestations     
Bronchitis * 1  8/139 (5.76%)  8/139 (5.76%) 
Conjunctivitis * 1  17/139 (12.23%)  9/139 (6.47%) 
Herpes Zoster * 1  10/139 (7.19%)  5/139 (3.60%) 
Nasopharyngitis * 1  16/139 (11.51%)  16/139 (11.51%) 
Oral Herpes * 1  4/139 (2.88%)  15/139 (10.79%) 
Paronychia * 1  9/139 (6.47%)  5/139 (3.60%) 
Pneumonia * 1  6/139 (4.32%)  14/139 (10.07%) 
Respiratory Tract Infection * 1  9/139 (6.47%)  14/139 (10.07%) 
Rhinitis * 1  8/139 (5.76%)  5/139 (3.60%) 
Sinusitis * 1  11/139 (7.91%)  6/139 (4.32%) 
Upper Respiratory Tract Infection * 1  28/139 (20.14%)  15/139 (10.79%) 
Urinary Tract Infection * 1  10/139 (7.19%)  7/139 (5.04%) 
Injury, poisoning and procedural complications     
Contusion * 1  10/139 (7.19%)  3/139 (2.16%) 
Investigations     
Alanine Aminotransferase Increased * 1  4/139 (2.88%)  9/139 (6.47%) 
Aspartate Aminotransferase Increased * 1  5/139 (3.60%)  10/139 (7.19%) 
Blood Alkaline Phosphatase Increased * 1  4/139 (2.88%)  9/139 (6.47%) 
Blood Creatinine Increased * 1  16/139 (11.51%)  18/139 (12.95%) 
Blood Lactate Dehydrogenase Increased * 1  2/139 (1.44%)  7/139 (5.04%) 
Neutrophil Count Decreased * 1  7/139 (5.04%)  10/139 (7.19%) 
Platelet Count Decreased * 1  11/139 (7.91%)  23/139 (16.55%) 
Weight Decreased * 1  9/139 (6.47%)  18/139 (12.95%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  26/139 (18.71%)  25/139 (17.99%) 
Diabetes Mellitus * 1  1/139 (0.72%)  7/139 (5.04%) 
Hypercholesterolaemia * 1  2/139 (1.44%)  18/139 (12.95%) 
Hyperglycaemia * 1  4/139 (2.88%)  26/139 (18.71%) 
Hyperkalaemia * 1  9/139 (6.47%)  3/139 (2.16%) 
Hypertriglyceridaemia * 1  1/139 (0.72%)  25/139 (17.99%) 
Hypokalaemia * 1  12/139 (8.63%)  24/139 (17.27%) 
Hypomagnesaemia * 1  9/139 (6.47%)  4/139 (2.88%) 
Hyponatraemia * 1  1/139 (0.72%)  7/139 (5.04%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  10/139 (7.19%)  9/139 (6.47%) 
Back Pain * 1  15/139 (10.79%)  14/139 (10.07%) 
Muscle Spasms * 1  26/139 (18.71%)  4/139 (2.88%) 
Pain in Extremity * 1  5/139 (3.60%)  12/139 (8.63%) 
Nervous system disorders     
Dysgeusia * 1  1/139 (0.72%)  7/139 (5.04%) 
Headache * 1  13/139 (9.35%)  17/139 (12.23%) 
Psychiatric disorders     
Insomnia * 1  7/139 (5.04%)  15/139 (10.79%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  31/139 (22.30%)  31/139 (22.30%) 
Dyspnoea * 1  12/139 (8.63%)  13/139 (9.35%) 
Epistaxis * 1  13/139 (9.35%)  31/139 (22.30%) 
Oropharyngeal Pain * 1  8/139 (5.76%)  8/139 (5.76%) 
Pleural Effusion * 1  10/139 (7.19%)  5/139 (3.60%) 
Pneumonitis * 1  0/139 (0.00%)  7/139 (5.04%) 
Productive Cough * 1  7/139 (5.04%)  5/139 (3.60%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  12/139 (8.63%)  18/139 (12.95%) 
Rash * 1  18/139 (12.95%)  25/139 (17.99%) 
Rash Generalised * 1  1/139 (0.72%)  7/139 (5.04%) 
Rash Maculo-Papular * 1  5/139 (3.60%)  7/139 (5.04%) 
Skin Lesion * 1  6/139 (4.32%)  8/139 (5.76%) 
Vascular disorders     
Haematoma * 1  11/139 (7.91%)  3/139 (2.16%) 
Hypertension * 1  16/139 (11.51%)  5/139 (3.60%) 
Hypotension * 1  7/139 (5.04%)  3/139 (2.16%) 
1
Term from vocabulary, MedDRA Version 18.1
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Janssen-Cilag International NV
EMail: ClinicalTrialDisclosure@its.jnj.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01646021    
Other Study ID Numbers: CR100848
PCI-32765MCL3001 ( Other Identifier: Janssen Research & Development, LLC )
2012-000601-74 ( EudraCT Number )
U1111-1135-6930 ( Other Identifier: Universal Trial Number )
First Submitted: July 18, 2012
First Posted: July 20, 2012
Results First Submitted: June 2, 2016
Results First Posted: March 1, 2017
Last Update Posted: January 19, 2018