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)

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ClinicalTrials.gov Identifier: NCT02470585

Recruitment Status : Terminated (Business decision not related to patient safety)

First Posted : June 12, 2015

Results First Posted : September 14, 2020

Last Update Posted : October 30, 2023

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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

Participant Flow

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
Arm/Group Description	Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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.

Baseline Characteristics

Arm/Group Title		Placebo + Carboplatin + Paclitaxel -> Placebo	Veliparib + Carboplatin + Paclitaxel -> Placebo	Veliparib + Carboplatin + Paclitaxel -> Veliparib	Total
Arm/Group Description		Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...	Total of all reporting groups
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
Baseline Analysis Population Description		...
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%

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival (PFS) in the BRCA-deficient Population
Description	PFS was defined as the time from the date that the participant was ran...
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.

Outcome Measure Data

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
Arm/Group Description:	Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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

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
Description	PFS was defined as the time from the date that the participant was ran...
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.

Outcome Measure Data

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
Arm/Group Description:	Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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)

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
Description	PFS was defined as the time from the date that the participant was ran...
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.

Outcome Measure Data

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
Arm/Group Description:	Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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)

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)
Description	OS is defined as the time from the day the participant was randomized ...
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
Description	The Disease Related Symptom score is a subset of the National Comprehe...
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

Outcome Measure Data

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
Arm/Group Description:		Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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
Cycle 3		1.8 (0.52)	0.5 (0.53)	0.9 (0.51)
Cycle 5	Number Analyzed	81 participants	80 participants	84 participants
Cycle 5		1.7 (0.57)	0.7 (0.58)	0.4 (0.56)
Cycle 7	Number Analyzed	78 participants	84 participants	83 participants
Cycle 7		2.6 (0.54)	1.8 (0.54)	1.8 (0.53)
Cycle 9	Number Analyzed	79 participants	80 participants	80 participants
Cycle 9		3.3 (0.60)	3.3 (0.60)	2.4 (0.59)
Cycle 11	Number Analyzed	73 participants	81 participants	82 participants
Cycle 11		3.2 (0.56)	3.6 (0.55)	2.9 (0.54)
Cycle 13	Number Analyzed	74 participants	80 participants	70 participants
Cycle 13		3.6 (0.57)	3.8 (0.57)	3.0 (0.57)
Cycle 15	Number Analyzed	69 participants	62 participants	69 participants
Cycle 15		4.3 (0.53)	4.0 (0.54)	3.4 (0.52)
Cycle 17	Number Analyzed	64 participants	65 participants	70 participants
Cycle 17		3.8 (0.56)	4.0 (0.57)	3.2 (0.55)
Cycle 19	Number Analyzed	58 participants	53 participants	66 participants
Cycle 19		4.0 (0.62)	4.0 (0.63)	2.7 (0.59)
Cycle 21	Number Analyzed	55 participants	56 participants	72 participants
Cycle 21		4.6 (0.59)	3.9 (0.59)	3.2 (0.55)
Cycle 23	Number Analyzed	47 participants	47 participants	59 participants
Cycle 23		4.3 (0.55)	4.0 (0.55)	2.8 (0.52)
Cycle 25	Number Analyzed	48 participants	45 participants	58 participants
Cycle 25		4.1 (0.58)	5.0 (0.59)	3.5 (0.55)
Cycle 27	Number Analyzed	41 participants	42 participants	53 participants
Cycle 27		4.6 (0.55)	4.8 (0.56)	3.0 (0.52)
Cycle 29	Number Analyzed	41 participants	39 participants	60 participants
Cycle 29		4.0 (0.66)	5.3 (0.66)	2.8 (0.59)
Cycle 31	Number Analyzed	35 participants	36 participants	51 participants
Cycle 31		5.0 (0.56)	4.8 (0.57)	2.9 (0.51)
Cycle 33	Number Analyzed	34 participants	37 participants	52 participants
Cycle 33		4.1 (0.67)	5.0 (0.66)	3.9 (0.59)
Cycle 35	Number Analyzed	32 participants	35 participants	42 participants
Cycle 35		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
Description	The Disease Related Symptom score is a subset of the National Comprehe...
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

Outcome Measure Data

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
Arm/Group Description:		Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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
Cycle 3		1.5 (0.35)	0.5 (0.36)	0.9 (0.35)
Cycle 5	Number Analyzed	178 participants	169 participants	172 participants
Cycle 5		1.7 (0.37)	1.1 (0.37)	0.8 (0.37)
Cycle 7	Number Analyzed	172 participants	168 participants	170 participants
Cycle 7		2.4 (0.35)	1.8 (0.36)	2.2 (0.35)
Cycle 9	Number Analyzed	173 participants	165 participants	165 participants
Cycle 9		3.3 (0.37)	3.6 (0.38)	2.3 (0.38)
Cycle 11	Number Analyzed	162 participants	161 participants	159 participants
Cycle 11		3.5 (0.36)	3.5 (0.36)	2.7 (0.36)
Cycle 13	Number Analyzed	160 participants	159 participants	134 participants
Cycle 13		3.6 (0.37)	3.8 (0.38)	2.7 (0.39)
Cycle 15	Number Analyzed	149 participants	137 participants	130 participants
Cycle 15		4.2 (0.35)	3.9 (0.36)	3.3 (0.37)
Cycle 17	Number Analyzed	139 participants	128 participants	124 participants
Cycle 17		3.9 (0.39)	3.4 (0.41)	3.0 (0.40)
Cycle 19	Number Analyzed	120 participants	107 participants	119 participants
Cycle 19		4.2 (0.40)	3.7 (0.42)	2.7 (0.41)
Cycle 21	Number Analyzed	115 participants	110 participants	118 participants
Cycle 21		4.6 (0.40)	3.6 (0.41)	3.0 (0.40)
Cycle 23	Number Analyzed	104 participants	95 participants	102 participants
Cycle 23		4.1 (0.38)	3.6 (0.39)	3.2 (0.38)
Cycle 25	Number Analyzed	98 participants	86 participants	96 participants
Cycle 25		4.1 (0.40)	4.4 (0.41)	3.5 (0.40)
Cycle 27	Number Analyzed	88 participants	81 participants	87 participants
Cycle 27		4.4 (0.39)	4.4 (0.40)	3.0 (0.38)
Cycle 29	Number Analyzed	86 participants	75 participants	96 participants
Cycle 29		4.2 (0.43)	4.7 (0.44)	3.2 (0.41)
Cycle 31	Number Analyzed	77 participants	72 participants	82 participants
Cycle 31		4.0 (0.41)	4.3 (0.42)	3.3 (0.40)
Cycle 33	Number Analyzed	68 participants	70 participants	81 participants
Cycle 33		4.3 (0.45)	4.7 (0.45)	3.9 (0.43)
Cycle 35	Number Analyzed	61 participants	60 participants	65 participants
Cycle 35		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
Description	The Disease Related Symptom score is a subset of the National Comprehe...
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

Outcome Measure Data

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
Arm/Group Description:		Participants received placebo to ve...	Participants received 150 mg velipa...	Participants received 150 mg velipa...
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
Cycle 3		1.5 (0.28)	0.4 (0.28)	1.0 (0.28)
Cycle 5	Number Analyzed	310 participants	311 participants	301 participants
Cycle 5		1.6 (0.29)	0.9 (0.29)	0.8 (0.29)
Cycle 7	Number Analyzed	301 participants	300 participants	287 participants
Cycle 7		2.3 (0.29)	1.8 (0.29)	2.1 (0.29)
Cycle 9	Number Analyzed	291 participants	290 participants	277 participants
Cycle 9		3.3 (0.29)	3.8 (0.29)	2.4 (0.29)
Cycle 11	Number Analyzed	269 participants	267 participants	249 participants
Cycle 11		3.5 (0.29)	4.0 (0.28)	3.0 (0.29)
Cycle 13	Number Analyzed	254 participants	254 participants	225 participants
Cycle 13		3.8 (0.30)	4.0 (0.30)	3.2 (0.30)
Cycle 15	Number Analyzed	224 participants	225 participants	207 participants
Cycle 15		4.2 (0.30)	3.8 (0.30)	3.3 (0.30)
Cycle 17	Number Analyzed	204 participants	202 participants	202 participants
Cycle 17		4.1 (0.32)	3.7 (0.32)	3.4 (0.32)
Cycle 19	Number Analyzed	177 participants	171 participants	178 participants
Cycle 19		4.4 (0.32)	4.0 (0.32)	3.1 (0.32)
Cycle 21	Number Analyzed	170 participants	160 participants	174 participants
Cycle 21		4.3 (0.34)	3.6 (0.34)	3.3 (0.33)
Cycle 23	Number Analyzed	150 participants	139 participants	153 participants
Cycle 23		4.0 (0.33)	3.9 (0.33)	3.4 (0.32)
Cycle 25	Number Analyzed	144 participants	127 participants	145 participants
Cycle 25		4.0 (0.34)	4.1 (0.35)	3.5 (0.33)
Cycle 27	Number Analyzed	129 participants	120 participants	130 participants
Cycle 27		4.4 (0.33)	4.2 (0.33)	3.5 (0.32)
Cycle 29	Number Analyzed	123 participants	113 participants	135 participants
Cycle 29		4.3 (0.35)	4.4 (0.35)	3.4 (0.33)
Cycle 31	Number Analyzed	111 participants	108 participants	118 participants
Cycle 31		4.0 (0.36)	4.1 (0.37)	3.3 (0.35)
Cycle 33	Number Analyzed	101 participants	100 participants	111 participants
Cycle 33		4.2 (0.38)	4.5 (0.38)	3.8 (0.36)
Cycle 35	Number Analyzed	91 participants	89 participants	90 participants
Cycle 35		4.4 (0.38)	4.2 (0.38)	3.8 (0.37)

Adverse Events

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
Arm/Group Description	Participants received placebo to ve...		Participants received 150 mg velipa...		Participants received 150 mg velipa...
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%)
Serious Adverse Events 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
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

Limitations and Caveats

[Not Specified]

More Information

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

Publications:

Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2403-2415. doi: 10.1056/NEJMoa1909707. Epub 2019 Sep 28.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Swisher EM, Aghajanian C, O'Malley DM, Fleming GF, Kaufmann SH, Levine DA, Birrer MJ, Moore KN, Spirtos NM, Shahin MS, Reid TJ, Friedlander M, Steffensen KD, Okamoto A, Sehgal V, Ansell PJ, Dinh MH, Bookman MA, Coleman RL. Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study. Gynecol Oncol. 2022 Feb;164(2):245-253. doi: 10.1016/j.ygyno.2021.12.003. Epub 2021 Dec 11.

Washington CR, Moore KN. PARP inhibitors in the treatment of ovarian cancer: a review. Curr Opin Obstet Gynecol. 2021 Feb 1;33(1):1-6. doi: 10.1097/GCO.0000000000000675.

Nishikawa T, Matsumoto K, Tamura K, Yoshida H, Imai Y, Miyasaka A, Onoe T, Yamaguchi S, Shimizu C, Yonemori K, Shimoi T, Yunokawa M, Xiong H, Nuthalapati S, Hashiba H, Kiriyama T, Leahy T, Komarnitsky P, Fujiwara K. Phase 1 dose-escalation study of single-agent veliparib in Japanese patients with advanced solid tumors. Cancer Sci. 2017 Sep;108(9):1834-1842. doi: 10.1111/cas.13307. Epub 2017 Aug 5.

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:	October 30, 2023

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