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Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (VELIA)

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: NCT02470585
Recruitment Status : Active, not recruiting
First Posted : June 12, 2015
Results First Posted : September 14, 2020
Last Update Posted : December 22, 2020
Sponsor:
Collaborator:
Gynecologic Oncology Group;Australia New Zealand Gynaecological Oncology Group
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Ovarian Cancer
Ovarian Neoplasm
Interventions Drug: Veliparib
Drug: Paclitaxel
Drug: Carboplatin
Other: Placebo to Veliparib
Enrollment 1140
Recruitment Details This trial was conducted at 188 sites in 10 countries (Australia, Brazil, Denmark, Israel, Japan, Poland, Republic of Korea, Spain, United Kingdom, and United States). The study is currently ongoing; the data-cutoff date for the primary analysis results reported below was May 3, 2019.
Pre-assignment Details Participants were randomized in a 1:1:1 ratio to one of three treatment groups. Randomization was stratified according to the timing of surgery and residual disease after primary surgery, the paclitaxel schedule, stage of disease, geographic region, and germline breast cancer susceptibility gene (BRCA) status.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve (AUC) of 6 milligrams per milliliter per minute (mg/mL/min) every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Period Title: Overall Study
Started [1] 375 383 382
Received Study Drug 371 376 377
Completed [2] 268 266 257
Not Completed 107 117 125
Reason Not Completed
Death             82             87             86
Withdrawal by Subject             19             21             29
Lost to Follow-up             2             5             4
Other             4             4             6
[1]
Started indicates the number of participants randomized.
[2]
Completed indicates participants remaining on study.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib Total
Hide Arm/Group Description

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Total of all reporting groups
Overall Number of Baseline Participants 375 383 382 1140
Hide Baseline Analysis Population Description
The intention-to-treat (ITT) population consisted of all randomized participants.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
62.0
(33.0 to 86.0)
62.0
(22.0 to 88.0)
62.0
(30.0 to 85.0)
62.0
(22.0 to 88.0)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
< 65 years
233
  62.1%
226
  59.0%
228
  59.7%
687
  60.3%
≥ 65 years
142
  37.9%
157
  41.0%
154
  40.3%
453
  39.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Female
375
 100.0%
383
 100.0%
382
 100.0%
1140
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Hispanic or Latino
28
   7.5%
27
   7.0%
26
   6.8%
81
   7.1%
Not Hispanic or Latino
347
  92.5%
356
  93.0%
356
  93.2%
1059
  92.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
White
299
  79.7%
297
  77.5%
300
  78.5%
896
  78.6%
Black or African American
10
   2.7%
13
   3.4%
20
   5.2%
43
   3.8%
Asian
59
  15.7%
69
  18.0%
56
  14.7%
184
  16.1%
American Indian or Alaska Native
1
   0.3%
1
   0.3%
1
   0.3%
3
   0.3%
Native Hawaiian or other Pacific Islander
1
   0.3%
0
   0.0%
2
   0.5%
3
   0.3%
Multi-race
3
   0.8%
0
   0.0%
0
   0.0%
3
   0.3%
Missing
2
   0.5%
3
   0.8%
3
   0.8%
8
   0.7%
Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
North America
266
  70.9%
261
  68.1%
267
  69.9%
794
  69.6%
Japan
23
   6.1%
30
   7.8%
25
   6.5%
78
   6.8%
Rest of World
86
  22.9%
92
  24.0%
90
  23.6%
268
  23.5%
BRCA-Deficient Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Germline or tissue BRCA1/2 mutation
92
  24.5%
98
  25.6%
108
  28.3%
298
  26.1%
Germline or tissue BRCA1/2 wildtype
254
  67.7%
243
  63.4%
245
  64.1%
742
  65.1%
Missing
29
   7.7%
42
  11.0%
29
   7.6%
100
   8.8%
[1]
Measure Description: The BRCA-mutation cohort was defined as participants who had deleterious or suspected deleterious germline (gBRCA) or tissue-based (tBRCA) mutations as determined by the Myriad BRACAnalysis® companion diagnostic (CDx) or myChoice® HRD CDx assay, respectively, in BRCA1 or BRCA2.
Homologous Recombination Deficiency (HRD) Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
HRD
207
  55.2%
206
  53.8%
214
  56.0%
627
  55.0%
Non-HRD
124
  33.1%
123
  32.1%
125
  32.7%
372
  32.6%
Missing
44
  11.7%
54
  14.1%
43
  11.3%
141
  12.4%
[1]
Measure Description: The HRD cohort consisted of participants who had tumors that were BRCA-mutated or had HRD according to the Myriad myChoice® assay, on which a score of ≥ 33 was considered to indicate HRD status, and a score of < 33 was considered to indicate non-HRD status.
Stage of Disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Stage III
292
  77.9%
288
  75.2%
295
  77.2%
875
  76.8%
Stage IV
82
  21.9%
94
  24.5%
87
  22.8%
263
  23.1%
Missing
1
   0.3%
1
   0.3%
0
   0.0%
2
   0.2%
[1]
Measure Description:

Staging of primary ovarian carcinomas according to the International Federation of Gynecology and Obstetrics (FIGO) criteria, based on clinical examination, surgical exploration, histologic characteristics and cytologic testing.

STAGE III: Tumor involves 1 or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastases to the retroperitoneal lymph nodes.

STAGE IV: Distant metastases excluding peritoneal metastases

Type of Surgery Received   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Primary
250
  66.7%
253
  66.1%
261
  68.3%
764
  67.0%
Interval
107
  28.5%
114
  29.8%
99
  25.9%
320
  28.1%
No surgery received
18
   4.8%
16
   4.2%
22
   5.8%
56
   4.9%
[1]
Measure Description: Cytoreductive surgery could be performed before randomization and the initiation of study treatment (primary) or after 3 cycles of study treatment (interval), determined at the discretion of the investigator.
Residual Disease After Primary Surgery   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 250 participants 253 participants 261 participants 764 participants
No residual disease
116
  46.4%
118
  46.6%
124
  47.5%
358
  46.9%
Microscopic residual disease only
58
  23.2%
46
  18.2%
54
  20.7%
158
  20.7%
Any macroscopic residual disease
76
  30.4%
89
  35.2%
83
  31.8%
248
  32.5%
[1]
Measure Description: Data were collected after interval surgery after cycle 3.
[2]
Measure Analysis Population Description: Participants who underwent primary surgery
Residual Disease After Interval Surgery   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 114 participants 99 participants 320 participants
No residual disease
50
  46.7%
46
  40.4%
45
  45.5%
141
  44.1%
Microscopic residual disease only
22
  20.6%
30
  26.3%
24
  24.2%
76
  23.8%
Any macroscopic residual disease
31
  29.0%
34
  29.8%
27
  27.3%
92
  28.7%
Missing
4
   3.7%
4
   3.5%
3
   3.0%
11
   3.4%
[1]
Measure Analysis Population Description: Participants who underwent interval surgery
Paclitaxel Dosing Regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Weekly
193
  51.5%
203
  53.0%
190
  49.7%
586
  51.4%
Every 3 weeks
179
  47.7%
178
  46.5%
189
  49.5%
546
  47.9%
Missing
3
   0.8%
2
   0.5%
3
   0.8%
8
   0.7%
Germline BRCA Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 375 participants 383 participants 382 participants 1140 participants
Germline BRCA1/2 mutation
63
  16.8%
71
  18.5%
80
  20.9%
214
  18.8%
Germline BRCA1/2 wildtype
305
  81.3%
305
  79.6%
298
  78.0%
908
  79.6%
Missing
7
   1.9%
7
   1.8%
4
   1.0%
18
   1.6%
1.Primary Outcome
Title Progression-Free Survival (PFS) in the BRCA-deficient Population
Hide Description

PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached.

Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.

Time Frame From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed in 3 sequentially inclusive populations. The first analysis was conducted using the BRCA-mutation cohort which included participants with either a gBRCA and/or tBRCA deleterious or suspected deleterious mutation in BRCA1 or BRCA2.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description:

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Overall Number of Participants Analyzed 92 98 108
Median (95% Confidence Interval)
Unit of Measure: months
22.0
(17.8 to 29.1)
21.1
(17.0 to 25.5)
34.7 [1] 
(31.8 to NA)
[1]
Could not be estimated due to the low number of events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Carboplatin + Paclitaxel -> Placebo, Veliparib + Carboplatin + Paclitaxel -> Veliparib
Comments The primary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -> Veliparib group vs. the Placebo + Carboplatin + Paclitaxel -> Placebo group.
Type of Statistical Test Superiority
Comments Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-mutation population, HRD population, and ITT population), and multiple endpoints. A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.
Statistical Test of Hypothesis P-Value <0.001
Comments A 2-sided p-value of ≤ 0.05 was considered statistically significant in the following hierarchical testing sequence: PFS was to be compared first in the BRCA-mutation cohort, then in the HRD cohort, and then in the ITT population.
Method Log Rank
Comments Stratified according to residual disease status and disease stage.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.435
Confidence Interval (2-Sided) 95%
0.277 to 0.683
Estimation Comments Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
2.Primary Outcome
Title Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort
Hide Description

PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations.

Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.

.

Time Frame From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed in 3 sequentially inclusive populations. The second analysis was conducted using the HRD cohort which included participants in the BRCA-mutation cohort and those determined to have HRD tumors.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description:

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Overall Number of Participants Analyzed 207 206 214
Median (95% Confidence Interval)
Unit of Measure: months
20.5
(17.8 to 22.8)
18.1
(16.4 to 22.7)
31.9
(25.8 to 38.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Carboplatin + Paclitaxel -> Placebo, Veliparib + Carboplatin + Paclitaxel -> Veliparib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-mutation population, HRD population, and ITT population), and multiple endpoints. A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.
Statistical Test of Hypothesis P-Value <0.001
Comments A 2-sided p-value of ≤ 0.05 was considered statistically significant in the following hierarchical testing sequence: PFS was to be compared first in the BRCA-mutation cohort, then in the HRD cohort, and then in the ITT population.
Method Log Rank
Comments Stratified according to residual disease status and disease stage.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.572
Confidence Interval (2-Sided) 95%
0.433 to 0.756
Estimation Comments Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
3.Primary Outcome
Title Progression-Free Survival (PFS) in the Intention-to-treat Population
Hide Description

PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method.

Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.

The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached.

Time Frame From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were performed in 3 sequentially inclusive populations. The third analysis was conducted using the intention-to-treat (ITT) population (all randomized participants).
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description:

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Overall Number of Participants Analyzed 375 383 382
Median (95% Confidence Interval)
Unit of Measure: months
17.3
(15.1 to 19.1)
15.2
(14.1 to 17.3)
23.5
(19.3 to 26.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Carboplatin + Paclitaxel -> Placebo, Veliparib + Carboplatin + Paclitaxel -> Veliparib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-mutation population, HRD population, and ITT population), and multiple endpoints. A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.
Statistical Test of Hypothesis P-Value <0.001
Comments A 2-sided p-value of ≤ 0.05 was considered statistically significant in the following hierarchical testing sequence: PFS was to be compared first in the BRCA-mutation cohort, then in the HRD cohort, and then in the ITT population.
Method Log Rank
Comments Stratified according to residual disease status and disease stage, choice of the paclitaxel regimen, and BRCA-mutation status
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.683
Confidence Interval (2-Sided) 95%
0.562 to 0.831
Estimation Comments Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description

OS is defined as the time from the day the participant was randomized to the date of death. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive.

The final analysis of OS will occur when the pre-specified number of events has occurred in the ITT and HRD populations.

Time Frame Approximately 8 years from randomization.
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population
Hide Description

The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.

Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.

DRS was not included in the fixed-sequence testing procedure.

Time Frame Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Hide Outcome Measure Data
Hide Analysis Population Description
BRCA-mutation population, participants with available data at each time point.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description:

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Overall Number of Participants Analyzed 92 98 108
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Cycle 3 Number Analyzed 87 participants 84 participants 92 participants
1.8  (0.52) 0.5  (0.53) 0.9  (0.51)
Cycle 5 Number Analyzed 81 participants 80 participants 84 participants
1.7  (0.57) 0.7  (0.58) 0.4  (0.56)
Cycle 7 Number Analyzed 78 participants 84 participants 83 participants
2.6  (0.54) 1.8  (0.54) 1.8  (0.53)
Cycle 9 Number Analyzed 79 participants 80 participants 80 participants
3.3  (0.60) 3.3  (0.60) 2.4  (0.59)
Cycle 11 Number Analyzed 73 participants 81 participants 82 participants
3.2  (0.56) 3.6  (0.55) 2.9  (0.54)
Cycle 13 Number Analyzed 74 participants 80 participants 70 participants
3.6  (0.57) 3.8  (0.57) 3.0  (0.57)
Cycle 15 Number Analyzed 69 participants 62 participants 69 participants
4.3  (0.53) 4.0  (0.54) 3.4  (0.52)
Cycle 17 Number Analyzed 64 participants 65 participants 70 participants
3.8  (0.56) 4.0  (0.57) 3.2  (0.55)
Cycle 19 Number Analyzed 58 participants 53 participants 66 participants
4.0  (0.62) 4.0  (0.63) 2.7  (0.59)
Cycle 21 Number Analyzed 55 participants 56 participants 72 participants
4.6  (0.59) 3.9  (0.59) 3.2  (0.55)
Cycle 23 Number Analyzed 47 participants 47 participants 59 participants
4.3  (0.55) 4.0  (0.55) 2.8  (0.52)
Cycle 25 Number Analyzed 48 participants 45 participants 58 participants
4.1  (0.58) 5.0  (0.59) 3.5  (0.55)
Cycle 27 Number Analyzed 41 participants 42 participants 53 participants
4.6  (0.55) 4.8  (0.56) 3.0  (0.52)
Cycle 29 Number Analyzed 41 participants 39 participants 60 participants
4.0  (0.66) 5.3  (0.66) 2.8  (0.59)
Cycle 31 Number Analyzed 35 participants 36 participants 51 participants
5.0  (0.56) 4.8  (0.57) 2.9  (0.51)
Cycle 33 Number Analyzed 34 participants 37 participants 52 participants
4.1  (0.67) 5.0  (0.66) 3.9  (0.59)
Cycle 35 Number Analyzed 32 participants 35 participants 42 participants
4.6  (0.64) 4.6  (0.63) 3.3  (0.58)
6.Secondary Outcome
Title Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population
Hide Description

The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.

Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.

DRS was not included in the fixed-sequence testing procedure.

Time Frame Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Hide Outcome Measure Data
Hide Analysis Population Description
HRD population, participants with available data at each time point.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description:

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Overall Number of Participants Analyzed 207 206 214
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Cycle 3 Number Analyzed 187 participants 179 participants 186 participants
1.5  (0.35) 0.5  (0.36) 0.9  (0.35)
Cycle 5 Number Analyzed 178 participants 169 participants 172 participants
1.7  (0.37) 1.1  (0.37) 0.8  (0.37)
Cycle 7 Number Analyzed 172 participants 168 participants 170 participants
2.4  (0.35) 1.8  (0.36) 2.2  (0.35)
Cycle 9 Number Analyzed 173 participants 165 participants 165 participants
3.3  (0.37) 3.6  (0.38) 2.3  (0.38)
Cycle 11 Number Analyzed 162 participants 161 participants 159 participants
3.5  (0.36) 3.5  (0.36) 2.7  (0.36)
Cycle 13 Number Analyzed 160 participants 159 participants 134 participants
3.6  (0.37) 3.8  (0.38) 2.7  (0.39)
Cycle 15 Number Analyzed 149 participants 137 participants 130 participants
4.2  (0.35) 3.9  (0.36) 3.3  (0.37)
Cycle 17 Number Analyzed 139 participants 128 participants 124 participants
3.9  (0.39) 3.4  (0.41) 3.0  (0.40)
Cycle 19 Number Analyzed 120 participants 107 participants 119 participants
4.2  (0.40) 3.7  (0.42) 2.7  (0.41)
Cycle 21 Number Analyzed 115 participants 110 participants 118 participants
4.6  (0.40) 3.6  (0.41) 3.0  (0.40)
Cycle 23 Number Analyzed 104 participants 95 participants 102 participants
4.1  (0.38) 3.6  (0.39) 3.2  (0.38)
Cycle 25 Number Analyzed 98 participants 86 participants 96 participants
4.1  (0.40) 4.4  (0.41) 3.5  (0.40)
Cycle 27 Number Analyzed 88 participants 81 participants 87 participants
4.4  (0.39) 4.4  (0.40) 3.0  (0.38)
Cycle 29 Number Analyzed 86 participants 75 participants 96 participants
4.2  (0.43) 4.7  (0.44) 3.2  (0.41)
Cycle 31 Number Analyzed 77 participants 72 participants 82 participants
4.0  (0.41) 4.3  (0.42) 3.3  (0.40)
Cycle 33 Number Analyzed 68 participants 70 participants 81 participants
4.3  (0.45) 4.7  (0.45) 3.9  (0.43)
Cycle 35 Number Analyzed 61 participants 60 participants 65 participants
4.0  (0.46) 4.6  (0.47) 3.3  (0.45)
7.Secondary Outcome
Title Change From Baseline in Disease Related Symptom (DRS) Score in the ITT Population
Hide Description

The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.

Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease, stage of disease, choice of paclitaxel dosing regimen and BRCA-deficient status, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.

DRS was not included in the fixed-sequence testing procedure.

Time Frame Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, participants with available data at each time point.
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description:

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Overall Number of Participants Analyzed 375 383 382
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Cycle 3 Number Analyzed 333 participants 332 participants 319 participants
1.5  (0.28) 0.4  (0.28) 1.0  (0.28)
Cycle 5 Number Analyzed 310 participants 311 participants 301 participants
1.6  (0.29) 0.9  (0.29) 0.8  (0.29)
Cycle 7 Number Analyzed 301 participants 300 participants 287 participants
2.3  (0.29) 1.8  (0.29) 2.1  (0.29)
Cycle 9 Number Analyzed 291 participants 290 participants 277 participants
3.3  (0.29) 3.8  (0.29) 2.4  (0.29)
Cycle 11 Number Analyzed 269 participants 267 participants 249 participants
3.5  (0.29) 4.0  (0.28) 3.0  (0.29)
Cycle 13 Number Analyzed 254 participants 254 participants 225 participants
3.8  (0.30) 4.0  (0.30) 3.2  (0.30)
Cycle 15 Number Analyzed 224 participants 225 participants 207 participants
4.2  (0.30) 3.8  (0.30) 3.3  (0.30)
Cycle 17 Number Analyzed 204 participants 202 participants 202 participants
4.1  (0.32) 3.7  (0.32) 3.4  (0.32)
Cycle 19 Number Analyzed 177 participants 171 participants 178 participants
4.4  (0.32) 4.0  (0.32) 3.1  (0.32)
Cycle 21 Number Analyzed 170 participants 160 participants 174 participants
4.3  (0.34) 3.6  (0.34) 3.3  (0.33)
Cycle 23 Number Analyzed 150 participants 139 participants 153 participants
4.0  (0.33) 3.9  (0.33) 3.4  (0.32)
Cycle 25 Number Analyzed 144 participants 127 participants 145 participants
4.0  (0.34) 4.1  (0.35) 3.5  (0.33)
Cycle 27 Number Analyzed 129 participants 120 participants 130 participants
4.4  (0.33) 4.2  (0.33) 3.5  (0.32)
Cycle 29 Number Analyzed 123 participants 113 participants 135 participants
4.3  (0.35) 4.4  (0.35) 3.4  (0.33)
Cycle 31 Number Analyzed 111 participants 108 participants 118 participants
4.0  (0.36) 4.1  (0.37) 3.3  (0.35)
Cycle 33 Number Analyzed 101 participants 100 participants 111 participants
4.2  (0.38) 4.5  (0.38) 3.8  (0.36)
Cycle 35 Number Analyzed 91 participants 89 participants 90 participants
4.4  (0.38) 4.2  (0.38) 3.8  (0.37)
Time Frame From the first dose of study drug and no more than 30 days after the last dose of any study treatment up to the data cut-off date of 03 May 2019; median duration of treatment with veliparib/placebo was 369 days (range: 1 to 840 days).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Hide Arm/Group Description

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

All-Cause Mortality
Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   82/371 (22.10%)      88/376 (23.40%)      88/377 (23.34%)    
Hide Serious Adverse Events
Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   141/371 (38.01%)      129/376 (34.31%)      141/377 (37.40%)    
Blood and lymphatic system disorders       
ANAEMIA  1  4/371 (1.08%)  4 13/376 (3.46%)  14 14/377 (3.71%)  18
FEBRILE NEUTROPENIA  1  9/371 (2.43%)  10 19/376 (5.05%)  20 15/377 (3.98%)  17
LEUKOPENIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
NEUTROPENIA  1  6/371 (1.62%)  9 16/376 (4.26%)  22 12/377 (3.18%)  16
THROMBOCYTOPENIA  1  3/371 (0.81%)  3 9/376 (2.39%)  12 10/377 (2.65%)  20
Cardiac disorders       
ACUTE CORONARY SYNDROME  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
ATRIAL FIBRILLATION  1  3/371 (0.81%)  3 1/376 (0.27%)  2 1/377 (0.27%)  1
MYOCARDIAL INFARCTION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
PALPITATIONS  1  0/371 (0.00%)  0 2/376 (0.53%)  2 0/377 (0.00%)  0
STRESS CARDIOMYOPATHY  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
SUPRAVENTRICULAR TACHYCARDIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
TACHYCARDIA  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
VENTRICULAR EXTRASYSTOLES  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
Endocrine disorders       
ADRENAL INSUFFICIENCY  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
HYPERTHYROIDISM  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
Eye disorders       
VISION BLURRED  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
Gastrointestinal disorders       
ABDOMINAL ADHESIONS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ABDOMINAL HERNIA  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
ABDOMINAL INCARCERATED HERNIA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
ABDOMINAL PAIN  1  5/371 (1.35%)  5 9/376 (2.39%)  10 9/377 (2.39%)  10
ABDOMINAL PAIN UPPER  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ASCITES  1  7/371 (1.89%)  9 2/376 (0.53%)  2 2/377 (0.53%)  2
COLITIS  1  1/371 (0.27%)  2 2/376 (0.53%)  2 1/377 (0.27%)  1
COLITIS ULCERATIVE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
CONSTIPATION  1  3/371 (0.81%)  3 5/376 (1.33%)  5 2/377 (0.53%)  2
DIARRHOEA  1  3/371 (0.81%)  3 4/376 (1.06%)  5 2/377 (0.53%)  2
DIVERTICULAR PERFORATION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
ENTEROCOLITIS  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
EPIPLOIC APPENDAGITIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
GASTRIC ULCER  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
GASTRIC VOLVULUS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
HAEMATEMESIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
HIATUS HERNIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ILEAL PERFORATION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
ILEUS  1  2/371 (0.54%)  2 7/376 (1.86%)  7 3/377 (0.80%)  4
INTESTINAL OBSTRUCTION  1  2/371 (0.54%)  4 1/376 (0.27%)  1 6/377 (1.59%)  7
INTESTINAL PERFORATION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
INTESTINAL PSEUDO-OBSTRUCTION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
INTRA-ABDOMINAL FLUID COLLECTION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
LARGE INTESTINAL OBSTRUCTION  1  1/371 (0.27%)  1 2/376 (0.53%)  3 1/377 (0.27%)  1
LARGE INTESTINE PERFORATION  1  2/371 (0.54%)  2 0/376 (0.00%)  0 0/377 (0.00%)  0
MECHANICAL ILEUS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
NAUSEA  1  4/371 (1.08%)  5 11/376 (2.93%)  11 13/377 (3.45%)  16
OESOPHAGITIS ULCERATIVE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
PANCREATITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
PANCREATITIS ACUTE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
PERITONEAL HAEMORRHAGE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
PNEUMOPERITONEUM  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
RECTAL HAEMORRHAGE  1  3/371 (0.81%)  3 0/376 (0.00%)  0 0/377 (0.00%)  0
SMALL INTESTINAL OBSTRUCTION  1  18/371 (4.85%)  21 13/376 (3.46%)  17 11/377 (2.92%)  14
SMALL INTESTINAL PERFORATION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
SPIGELIAN HERNIA  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
UPPER GASTROINTESTINAL HAEMORRHAGE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
VOMITING  1  5/371 (1.35%)  5 10/376 (2.66%)  10 12/377 (3.18%)  16
General disorders       
ASTHENIA  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
CHEST DISCOMFORT  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
CHEST PAIN  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
CHILLS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 2/377 (0.53%)  2
DISEASE PROGRESSION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
FATIGUE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 2/377 (0.53%)  3
HERNIA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
INCARCERATED HERNIA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
NON-CARDIAC CHEST PAIN  1  1/371 (0.27%)  1 0/376 (0.00%)  0 4/377 (1.06%)  4
PAIN  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
PELVIC MASS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
PYREXIA  1  6/371 (1.62%)  6 3/376 (0.80%)  3 9/377 (2.39%)  9
Hepatobiliary disorders       
BILE DUCT STONE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
CHOLECYSTITIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
CHOLECYSTITIS ACUTE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 2/377 (0.53%)  2
Immune system disorders       
ANAPHYLACTIC REACTION  1  1/371 (0.27%)  1 1/376 (0.27%)  1 1/377 (0.27%)  1
DRUG HYPERSENSITIVITY  1  1/371 (0.27%)  1 2/376 (0.53%)  2 2/377 (0.53%)  2
Infections and infestations       
ABDOMINAL ABSCESS  1  1/371 (0.27%)  1 3/376 (0.80%)  3 1/377 (0.27%)  1
BACTERAEMIA  1  1/371 (0.27%)  1 1/376 (0.27%)  1 1/377 (0.27%)  1
BACTEROIDES BACTERAEMIA  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
BRONCHITIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
CATHETER SITE INFECTION  1  3/371 (0.81%)  3 0/376 (0.00%)  0 0/377 (0.00%)  0
CELLULITIS  1  1/371 (0.27%)  1 2/376 (0.53%)  2 1/377 (0.27%)  1
CLOSTRIDIUM DIFFICILE COLITIS  1  0/371 (0.00%)  0 2/376 (0.53%)  2 1/377 (0.27%)  1
CLOSTRIDIUM DIFFICILE INFECTION  1  3/371 (0.81%)  4 1/376 (0.27%)  1 1/377 (0.27%)  1
COLONIC ABSCESS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
CYSTITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
DEVICE RELATED INFECTION  1  2/371 (0.54%)  2 0/376 (0.00%)  0 0/377 (0.00%)  0
DIVERTICULITIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
EMPYEMA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ENDOCARDITIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ENTEROBACTER INFECTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
ENTEROCOCCAL BACTERAEMIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ENTEROCOLITIS INFECTIOUS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  2
ERYSIPELAS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
ESCHERICHIA INFECTION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
ESCHERICHIA URINARY TRACT INFECTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
GASTROENTERITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
GASTROENTERITIS VIRAL  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
GROIN ABSCESS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
HERPES ZOSTER  1  2/371 (0.54%)  2 0/376 (0.00%)  0 0/377 (0.00%)  0
INFECTED LYMPHOCELE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 2/377 (0.53%)  2
INFECTIOUS COLITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
INFLUENZA  1  0/371 (0.00%)  0 3/376 (0.80%)  3 3/377 (0.80%)  3
INTERVERTEBRAL DISCITIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
LUNG INFECTION  1  2/371 (0.54%)  3 0/376 (0.00%)  0 1/377 (0.27%)  1
LYMPHANGITIS  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
MENINGITIS CRYPTOCOCCAL  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
MYCOBACTERIAL INFECTION  1  0/371 (0.00%)  0 1/376 (0.27%)  2 0/377 (0.00%)  0
NAIL INFECTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
NASOPHARYNGITIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
NEUTROPENIC SEPSIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
OPHTHALMIC HERPES ZOSTER  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  2
OSTEOMYELITIS  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
OTITIS MEDIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
PELVIC ABSCESS  1  1/371 (0.27%)  1 2/376 (0.53%)  2 1/377 (0.27%)  1
PELVIC INFECTION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
PERIORBITAL CELLULITIS  1  0/371 (0.00%)  0 1/376 (0.27%)  2 0/377 (0.00%)  0
PERITONEAL ABSCESS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 1/377 (0.27%)  1
PERITONITIS  1  2/371 (0.54%)  2 0/376 (0.00%)  0 0/377 (0.00%)  0
PERITONITIS BACTERIAL  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
PHARYNGITIS STREPTOCOCCAL  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
PHLEBITIS INFECTIVE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
PNEUMONIA  1  4/371 (1.08%)  4 5/376 (1.33%)  5 3/377 (0.80%)  4
POST PROCEDURAL INFECTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
POSTOPERATIVE ABSCESS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
POSTOPERATIVE WOUND INFECTION  1  1/371 (0.27%)  1 2/376 (0.53%)  2 1/377 (0.27%)  2
PYELONEPHRITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
PYELONEPHRITIS ACUTE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 2/377 (0.53%)  2
RESPIRATORY TRACT INFECTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
SEPSIS  1  7/371 (1.89%)  7 2/376 (0.53%)  2 4/377 (1.06%)  5
SEPTIC EMBOLUS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
SEPTIC SHOCK  1  5/371 (1.35%)  6 3/376 (0.80%)  3 4/377 (1.06%)  5
STAPHYLOCOCCAL INFECTION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
STAPHYLOCOCCAL SEPSIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
SUBCUTANEOUS ABSCESS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
SUBDIAPHRAGMATIC ABSCESS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
SYSTEMIC CANDIDA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  0/371 (0.00%)  0 2/376 (0.53%)  2 2/377 (0.53%)  2
URINARY TRACT INFECTION  1  4/371 (1.08%)  5 6/376 (1.60%)  6 7/377 (1.86%)  7
UROSEPSIS  1  1/371 (0.27%)  1 1/376 (0.27%)  1 1/377 (0.27%)  1
VIRAL INFECTION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
WOUND INFECTION  1  2/371 (0.54%)  2 2/376 (0.53%)  2 0/377 (0.00%)  0
Injury, poisoning and procedural complications       
ACETABULUM FRACTURE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
ANASTOMOTIC LEAK  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
ANKLE FRACTURE  1  2/371 (0.54%)  2 0/376 (0.00%)  0 0/377 (0.00%)  0
CONCUSSION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
FALL  1  7/371 (1.89%)  7 0/376 (0.00%)  0 0/377 (0.00%)  0
FEMUR FRACTURE  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
FRACTURED SACRUM  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
GASTROINTESTINAL STOMA COMPLICATION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
HEAT ILLNESS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
INCISIONAL HERNIA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
INTESTINAL ANASTOMOSIS COMPLICATION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
JOINT DISLOCATION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
LUMBAR VERTEBRAL FRACTURE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
MULTIPLE INJURIES  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
PELVIC FRACTURE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
POST PROCEDURAL HAEMORRHAGE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
PROCEDURAL COMPLICATION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
RIB FRACTURE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
SKELETAL INJURY  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
SPINAL COMPRESSION FRACTURE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
SPINAL FRACTURE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
THORACIC VERTEBRAL FRACTURE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
VAGINAL CUFF DEHISCENCE  1  0/371 (0.00%)  0 1/376 (0.27%)  2 0/377 (0.00%)  0
WOUND COMPLICATION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
WOUND DECOMPOSITION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
WOUND DEHISCENCE  1  1/371 (0.27%)  1 1/376 (0.27%)  1 1/377 (0.27%)  1
Investigations       
INTERNATIONAL NORMALISED RATIO INCREASED  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
SOLUBLE FIBRIN MONOMER COMPLEX INCREASED  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Metabolism and nutrition disorders       
DECREASED APPETITE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
DEHYDRATION  1  6/371 (1.62%)  6 0/376 (0.00%)  0 6/377 (1.59%)  6
DIABETES MELLITUS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
HYPERKALAEMIA  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
HYPOALBUMINAEMIA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
HYPOCALCAEMIA  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
HYPOKALAEMIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 3/377 (0.80%)  3
HYPONATRAEMIA  1  2/371 (0.54%)  2 1/376 (0.27%)  1 6/377 (1.59%)  7
Musculoskeletal and connective tissue disorders       
FLANK PAIN  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
INTERVERTEBRAL DISC PROTRUSION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
MUSCULAR WEAKNESS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
OSTEOARTHRITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
ACUTE MYELOID LEUKAEMIA  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
MALIGNANT NEOPLASM PROGRESSION  1  14/371 (3.77%)  14 10/376 (2.66%)  11 3/377 (0.80%)  4
MALIGNANT PLEURAL EFFUSION  1  0/371 (0.00%)  0 2/376 (0.53%)  2 0/377 (0.00%)  0
METASTASES TO CENTRAL NERVOUS SYSTEM  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
NEOPLASM MALIGNANT  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
OVARIAN CANCER  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Nervous system disorders       
CEREBRAL ARTERY EMBOLISM  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
CEREBRAL INFARCTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
CEREBROVASCULAR ACCIDENT  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
HEADACHE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
HYPERSOMNIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
INTRACRANIAL VENOUS SINUS THROMBOSIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
LOSS OF CONSCIOUSNESS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
MIGRAINE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
MIGRAINE WITH AURA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
NEURALGIA  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
SYNCOPE  1  6/371 (1.62%)  6 1/376 (0.27%)  1 6/377 (1.59%)  6
TRANSIENT ISCHAEMIC ATTACK  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
Product Issues       
DEVICE BREAKAGE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
DEVICE DISLOCATION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Psychiatric disorders       
ANXIETY  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
CONFUSIONAL STATE  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
DEPRESSION  1  0/371 (0.00%)  0 1/376 (0.27%)  1 1/377 (0.27%)  1
MENTAL STATUS CHANGES  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
SUICIDE ATTEMPT  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
Renal and urinary disorders       
ACUTE KIDNEY INJURY  1  2/371 (0.54%)  2 1/376 (0.27%)  1 2/377 (0.53%)  2
HAEMATURIA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 1/377 (0.27%)  1
HYDRONEPHROSIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
RENAL VEIN THROMBOSIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
URETEROLITHIASIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
URINARY RETENTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Reproductive system and breast disorders       
FEMALE GENITAL TRACT FISTULA  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
VAGINAL HAEMORRHAGE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Respiratory, thoracic and mediastinal disorders       
ACUTE RESPIRATORY DISTRESS SYNDROME  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
ACUTE RESPIRATORY FAILURE  1  1/371 (0.27%)  1 1/376 (0.27%)  1 0/377 (0.00%)  0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
COUGH  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
DYSPNOEA  1  1/371 (0.27%)  1 2/376 (0.53%)  2 1/377 (0.27%)  1
DYSPNOEA EXERTIONAL  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
HAEMOPTYSIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
PLEURAL EFFUSION  1  4/371 (1.08%)  4 7/376 (1.86%)  7 0/377 (0.00%)  0
PNEUMONIA ASPIRATION  1  2/371 (0.54%)  2 1/376 (0.27%)  1 1/377 (0.27%)  1
PNEUMOTHORAX  1  0/371 (0.00%)  0 2/376 (0.53%)  2 0/377 (0.00%)  0
PNEUMOTHORAX SPONTANEOUS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
PULMONARY EMBOLISM  1  10/371 (2.70%)  10 10/376 (2.66%)  11 12/377 (3.18%)  13
PULMONARY THROMBOSIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
RESPIRATORY FAILURE  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
RESPIRATORY TRACT CONGESTION  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
Vascular disorders       
DEEP VEIN THROMBOSIS  1  2/371 (0.54%)  2 2/376 (0.53%)  2 4/377 (1.06%)  4
EMBOLISM  1  1/371 (0.27%)  1 0/376 (0.00%)  0 1/377 (0.27%)  1
HYPERTENSION  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
HYPOTENSION  1  1/371 (0.27%)  1 2/376 (0.53%)  2 1/377 (0.27%)  1
JUGULAR VEIN THROMBOSIS  1  2/371 (0.54%)  2 0/376 (0.00%)  0 2/377 (0.53%)  2
LYMPHOCELE  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
PHLEBITIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
SUBCLAVIAN VEIN THROMBOSIS  1  1/371 (0.27%)  1 0/376 (0.00%)  0 0/377 (0.00%)  0
THROMBOPHLEBITIS  1  0/371 (0.00%)  0 1/376 (0.27%)  1 0/377 (0.00%)  0
VENOUS THROMBOSIS  1  0/371 (0.00%)  0 0/376 (0.00%)  0 1/377 (0.27%)  1
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   369/371 (99.46%)      375/376 (99.73%)      376/377 (99.73%)    
Blood and lymphatic system disorders       
ANAEMIA  1  191/371 (51.48%)  513 232/376 (61.70%)  597 226/377 (59.95%)  657
LEUKOPENIA  1  89/371 (23.99%)  223 86/376 (22.87%)  260 112/377 (29.71%)  325
LYMPHOPENIA  1  15/371 (4.04%)  28 15/376 (3.99%)  20 26/377 (6.90%)  57
NEUTROPENIA  1  245/371 (66.04%)  680 265/376 (70.48%)  875 272/377 (72.15%)  840
THROMBOCYTOPENIA  1  119/371 (32.08%)  266 216/376 (57.45%)  626 209/377 (55.44%)  721
Eye disorders       
VISION BLURRED  1  31/371 (8.36%)  33 19/376 (5.05%)  22 27/377 (7.16%)  27
Gastrointestinal disorders       
ABDOMINAL DISTENSION  1  45/371 (12.13%)  55 48/376 (12.77%)  54 34/377 (9.02%)  39
ABDOMINAL PAIN  1  113/371 (30.46%)  162 104/376 (27.66%)  142 118/377 (31.30%)  162
ABDOMINAL PAIN UPPER  1  29/371 (7.82%)  38 18/376 (4.79%)  24 28/377 (7.43%)  36
CONSTIPATION  1  157/371 (42.32%)  203 176/376 (46.81%)  238 163/377 (43.24%)  225
DIARRHOEA  1  149/371 (40.16%)  246 136/376 (36.17%)  225 164/377 (43.50%)  254
DRY MOUTH  1  19/371 (5.12%)  20 10/376 (2.66%)  12 22/377 (5.84%)  23
DYSPEPSIA  1  41/371 (11.05%)  54 45/376 (11.97%)  55 35/377 (9.28%)  41
GASTROOESOPHAGEAL REFLUX DISEASE  1  22/371 (5.93%)  23 28/376 (7.45%)  30 35/377 (9.28%)  47
NAUSEA  1  247/371 (66.58%)  425 258/376 (68.62%)  432 289/377 (76.66%)  575
STOMATITIS  1  51/371 (13.75%)  66 47/376 (12.50%)  52 59/377 (15.65%)  67
VOMITING  1  127/371 (34.23%)  210 123/376 (32.71%)  169 174/377 (46.15%)  308
General disorders       
ASTHENIA  1  28/371 (7.55%)  58 36/376 (9.57%)  55 41/377 (10.88%)  64
FATIGUE  1  222/371 (59.84%)  355 235/376 (62.50%)  407 257/377 (68.17%)  450
INFLUENZA LIKE ILLNESS  1  17/371 (4.58%)  19 19/376 (5.05%)  26 9/377 (2.39%)  12
MALAISE  1  21/371 (5.66%)  34 20/376 (5.32%)  28 31/377 (8.22%)  37
MUCOSAL INFLAMMATION  1  19/371 (5.12%)  21 16/376 (4.26%)  18 18/377 (4.77%)  21
OEDEMA PERIPHERAL  1  73/371 (19.68%)  84 57/376 (15.16%)  61 56/377 (14.85%)  76
PAIN  1  23/371 (6.20%)  26 22/376 (5.85%)  31 21/377 (5.57%)  23
PYREXIA  1  24/371 (6.47%)  27 33/376 (8.78%)  37 22/377 (5.84%)  29
Immune system disorders       
DRUG HYPERSENSITIVITY  1  64/371 (17.25%)  84 48/376 (12.77%)  64 53/377 (14.06%)  58
Infections and infestations       
NASOPHARYNGITIS  1  22/371 (5.93%)  27 18/376 (4.79%)  21 25/377 (6.63%)  30
SINUSITIS  1  18/371 (4.85%)  26 18/376 (4.79%)  20 21/377 (5.57%)  22
UPPER RESPIRATORY TRACT INFECTION  1  44/371 (11.86%)  54 29/376 (7.71%)  37 34/377 (9.02%)  43
URINARY TRACT INFECTION  1  67/371 (18.06%)  104 64/376 (17.02%)  90 69/377 (18.30%)  90
Injury, poisoning and procedural complications       
CONTUSION  1  13/371 (3.50%)  13 17/376 (4.52%)  21 20/377 (5.31%)  28
PROCEDURAL PAIN  1  38/371 (10.24%)  47 18/376 (4.79%)  19 25/377 (6.63%)  25
Investigations       
ALANINE AMINOTRANSFERASE INCREASED  1  41/371 (11.05%)  64 30/376 (7.98%)  54 40/377 (10.61%)  52
ASPARTATE AMINOTRANSFERASE INCREASED  1  31/371 (8.36%)  46 21/376 (5.59%)  39 31/377 (8.22%)  35
BLOOD ALKALINE PHOSPHATASE INCREASED  1  19/371 (5.12%)  26 10/376 (2.66%)  13 16/377 (4.24%)  21
WEIGHT DECREASED  1  32/371 (8.63%)  45 41/376 (10.90%)  52 54/377 (14.32%)  71
WEIGHT INCREASED  1  35/371 (9.43%)  48 26/376 (6.91%)  34 36/377 (9.55%)  51
Metabolism and nutrition disorders       
DECREASED APPETITE  1  85/371 (22.91%)  101 81/376 (21.54%)  105 110/377 (29.18%)  141
DEHYDRATION  1  20/371 (5.39%)  21 32/376 (8.51%)  48 30/377 (7.96%)  36
HYPERGLYCAEMIA  1  18/371 (4.85%)  35 17/376 (4.52%)  25 27/377 (7.16%)  50
HYPOALBUMINAEMIA  1  19/371 (5.12%)  31 11/376 (2.93%)  16 16/377 (4.24%)  31
HYPOCALCAEMIA  1  15/371 (4.04%)  26 13/376 (3.46%)  16 19/377 (5.04%)  40
HYPOKALAEMIA  1  69/371 (18.60%)  107 66/376 (17.55%)  109 59/377 (15.65%)  94
HYPOMAGNESAEMIA  1  98/371 (26.42%)  198 94/376 (25.00%)  140 84/377 (22.28%)  141
HYPONATRAEMIA  1  25/371 (6.74%)  33 19/376 (5.05%)  22 25/377 (6.63%)  34
HYPOPHOSPHATAEMIA  1  21/371 (5.66%)  30 14/376 (3.72%)  17 11/377 (2.92%)  14
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  123/371 (33.15%)  189 106/376 (28.19%)  142 106/377 (28.12%)  152
BACK PAIN  1  66/371 (17.79%)  88 66/376 (17.55%)  75 66/377 (17.51%)  86
BONE PAIN  1  27/371 (7.28%)  46 26/376 (6.91%)  37 33/377 (8.75%)  36
MUSCULAR WEAKNESS  1  23/371 (6.20%)  28 24/376 (6.38%)  34 23/377 (6.10%)  33
MUSCULOSKELETAL PAIN  1  24/371 (6.47%)  30 16/376 (4.26%)  16 13/377 (3.45%)  15
MYALGIA  1  75/371 (20.22%)  106 59/376 (15.69%)  80 69/377 (18.30%)  96
PAIN IN EXTREMITY  1  55/371 (14.82%)  68 46/376 (12.23%)  56 50/377 (13.26%)  63
Nervous system disorders       
DIZZINESS  1  89/371 (23.99%)  119 81/376 (21.54%)  103 98/377 (25.99%)  123
DYSGEUSIA  1  73/371 (19.68%)  89 62/376 (16.49%)  73 89/377 (23.61%)  99
HEADACHE  1  97/371 (26.15%)  136 90/376 (23.94%)  124 97/377 (25.73%)  139
PERIPHERAL SENSORY NEUROPATHY  1  256/371 (69.00%)  413 236/376 (62.77%)  347 242/377 (64.19%)  371
TREMOR  1  9/371 (2.43%)  11 7/376 (1.86%)  8 23/377 (6.10%)  26
Psychiatric disorders       
ANXIETY  1  57/371 (15.36%)  71 62/376 (16.49%)  75 58/377 (15.38%)  69
DEPRESSION  1  40/371 (10.78%)  47 46/376 (12.23%)  58 34/377 (9.02%)  42
INSOMNIA  1  87/371 (23.45%)  103 121/376 (32.18%)  142 110/377 (29.18%)  135
Renal and urinary disorders       
DYSURIA  1  22/371 (5.93%)  24 18/376 (4.79%)  19 16/377 (4.24%)  17
Respiratory, thoracic and mediastinal disorders       
COUGH  1  58/371 (15.63%)  70 57/376 (15.16%)  63 58/377 (15.38%)  68
DYSPNOEA  1  75/371 (20.22%)  106 90/376 (23.94%)  110 83/377 (22.02%)  109
EPISTAXIS  1  59/371 (15.90%)  70 61/376 (16.22%)  66 55/377 (14.59%)  60
NASAL CONGESTION  1  26/371 (7.01%)  30 6/376 (1.60%)  6 18/377 (4.77%)  22
OROPHARYNGEAL PAIN  1  38/371 (10.24%)  45 24/376 (6.38%)  27 27/377 (7.16%)  32
Skin and subcutaneous tissue disorders       
ALOPECIA  1  215/371 (57.95%)  272 216/376 (57.45%)  271 197/377 (52.25%)  255
NAIL DISCOLOURATION  1  20/371 (5.39%)  20 10/376 (2.66%)  10 12/377 (3.18%)  12
PRURITUS  1  38/371 (10.24%)  45 32/376 (8.51%)  36 25/377 (6.63%)  29
RASH  1  54/371 (14.56%)  67 52/376 (13.83%)  62 47/377 (12.47%)  52
RASH MACULO-PAPULAR  1  31/371 (8.36%)  36 11/376 (2.93%)  15 22/377 (5.84%)  31
Vascular disorders       
HOT FLUSH  1  49/371 (13.21%)  53 44/376 (11.70%)  48 42/377 (11.14%)  49
HYPERTENSION  1  37/371 (9.97%)  65 38/376 (10.11%)  61 31/377 (8.22%)  55
1
Term from vocabulary, MedDRA 21.1
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.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: AbbVie
Phone: 1-800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02470585    
Other Study ID Numbers: M13-694
2014-005070-11 ( EudraCT Number )
First Submitted: June 10, 2015
First Posted: June 12, 2015
Results First Submitted: August 4, 2020
Results First Posted: September 14, 2020
Last Update Posted: December 22, 2020