Trial Outcomes & Findings for A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma (NCT NCT00804908)

Last Updated: 2018-06-06

Results Overview

PFS: the number of days from the date that the participant was randomized to the date the participant experienced a confirmed event of disease progression (radiological, as determined by the central imaging center; or clinical, as determined by the investigator), or to the date of death (all causes of mortality) if disease progression was not reached. All events were included whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced a confirmed event of disease progression, provided the death occurred within 8 weeks of the last available disease progression assessment. The distribution of PFS, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the quartiles for the PFS distribution are provided.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

346 participants

Primary outcome timeframe

Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Results posted on

2018-06-06

Participant Flow

A total of 346 subjects were randomized; 2 subjects did not receive study drug and were excluded from the safety analysis.

Participant milestones

Participant milestones
Measure	Placebo for ABT-888 BID + TMZ QD Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 20 mg BID + TMZ QD ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Overall Study STARTED	115	116	115
Overall Study COMPLETED	0	0	1
Overall Study NOT COMPLETED	115	116	114

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo for ABT-888 BID + TMZ QD Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 20 mg BID + TMZ QD ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Overall Study Other	115	116	114

Baseline Characteristics

A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Total n=346 Participants Total of all reporting groups
Age, Continuous	58.4 years STANDARD_DEVIATION 14.13 • n=5 Participants	58.6 years STANDARD_DEVIATION 12.55 • n=7 Participants	62.3 years STANDARD_DEVIATION 13.50 • n=5 Participants	59.8 years STANDARD_DEVIATION 13.49 • n=4 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	45 Participants n=7 Participants	38 Participants n=5 Participants	119 Participants n=4 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	71 Participants n=7 Participants	77 Participants n=5 Participants	227 Participants n=4 Participants

PRIMARY outcome

Timeframe: Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Population: ITT population defined as all randomized participants.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Progression-Free Survival (PFS): Time to Event 25th Percentile	56 days Interval 53.0 to 58.0	54 days Interval 50.0 to 56.0	53 days Interval 51.0 to 56.0
Progression-Free Survival (PFS): Time to Event 50th Percentile	113 days Interval 92.0 to 168.0	60 days Interval 57.0 to 111.0	110 days Interval 57.0 to 125.0
Progression-Free Survival (PFS): Time to Event 75th Percentile	225 days Interval 169.0 to NA=Not calculable due to insufficient progression events	163 days Interval 113.0 to 283.0	226 days Interval 173.0 to NA=Not calculable due to insufficient progression events

SECONDARY outcome

Timeframe: Per protocol, survival follow-up information was to be obtained every 3 months for up to 18 months after the final visit for the subject. The maximum observed follow-up at the overall survival analysis time was 21.0 months.

Population: ITT population defined as all randomized participants.

OS was defined as the number of days from the date the participant was randomized to the date of death. All deaths were included, whether the participant was still taking or had discontinued study drug. If a participant had not died and was lost to follow-up, then data were censored at the last study visit or contact date, or date the participant was last known to be alive, whichever was later; if the participant was not lost to follow-up, then data were censored at the last study visit or contact date, whichever was later. The distribution of OS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the OS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Overall Survival (OS): Time to Event 25th Percentile	204 days Interval 175.0 to 247.0	207 days Interval 155.0 to 241.0	181 days Interval 154.0 to 266.0
Overall Survival (OS): Time to Event 50th percentile	327 days Interval 274.0 to 399.0	390 days Interval 299.0 to 436.0	412 days Interval 346.0 to 483.0
Overall Survival (OS): Time to Event 75th percentile	NA days Interval 492.0 to NA=Not calculable due to insufficient survival events	559 days Interval 476.0 to 598.0	NA days NA=Not calculable due to insufficient survival events

SECONDARY outcome

Timeframe: Per protocol, survival was to be assessed every 4 weeks or as needed after participant is registered as off-study for up to 18 months. The maximum observed follow-up at the overall survival analysis time was 21.0 months.

Population: ITT population defined as all randomized participants.

The 12-month overall survival rate was defined as the percentage of participants surviving at 12 months. The distribution of 12-month OS rate was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
12-Month Overall Survival (OS) Rate	43.5 percentage of participants Interval 34.3 to 52.3	52.6 percentage of participants Interval 43.1 to 61.3	54.1 percentage of participants Interval 44.5 to 62.7

SECONDARY outcome

Population: ITT population defined as all randomized participants.

The 6-month progression-free survival rate was defined as the percentage of participants without disease progression at 6 months.The distribution of 6-month progression-free survival rate, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
6-month Progression-Free Survival Rate	32.8 percentage of participants Interval 22.0 to 44.1	19.1 percentage of participants Interval 10.9 to 29.0	30.7 percentage of participants Interval 20.3 to 41.7

SECONDARY outcome

Timeframe: Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Population: All subjects in the ITT population (defined as all randomized participants) with measurable disease.

The objective response rate was defined as the percentage of participants with a confirmed CR or PR per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by computed tomography (CT) scan: complete response (CR), disappearance of all target lesions; partial response (PR), ≥30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Objective Response Rate	10.3 percentage of participants Interval 5.5 to 17.4	7.0 percentage of participants Interval 3.1 to 13.2	9.6 percentage of participants Interval 4.9 to 16.5

SECONDARY outcome

Timeframe: Every Cycle (28 Days), until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Population: ITT population defined as all randomized participants.

The distribution of time to disease progression, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Time to Disease Progression 25th Percentile	56 days Interval 53.0 to 57.0	54 days Interval 50.0 to 56.0	53 days Interval 51.0 to 56.0
Time to Disease Progression 50th percentile	113 days Interval 92.0 to 168.0	60 days Interval 57.0 to 111.0	110 days Interval 57.0 to 125.0
Time to Disease Progression 75th percentile	225 days Interval 169.0 to NA=Not calculable due to insufficient progression events	163 days Interval 113.0 to 283.0	226 days Interval 173.0 to NA=Not calculable due to insufficient progression events

SECONDARY outcome

Timeframe: Week 8

Population: ITT population defined as all randomized participants.

The disease control rate was defined as the percentage of participants who had at least stable disease (complete response, partial response, or stable disease) through the end of Week 8. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Disease Control Rate	62.9 percentage of participants Interval 53.5 to 71.7	48.7 percentage of participants Interval 39.3 to 58.2	59.1 percentage of participants Interval 49.6 to 68.2

SECONDARY outcome

Population: ITT population defined as all randomized participants.

Time to neurological/brain metastases progression, defined as the number of days from the date of randomization to the date the participant experienced an event of neurological/brain metastases progression, was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the distribution are provided. All events of progression were included, regardless of whether the event occurred while the participant was still taking study drug. If a participant did not experience an event, data were censored at the date of the last available brain CT scan. For participants with no postbaseline brain CT scans, data were censored at randomization. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values.

Outcome measures

Outcome measures
Measure	ABT-888 20 mg BID + TMZ QD n=116 Participants ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	Placebo for ABT-888 BID + TMZ QD n=115 Participants Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 Participants ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Time to Neurological/Brain Metastases Progression 25th Percentile	119 days Interval 48.0 to NA=Not calculable due to insufficient progression events	60 days Interval 34.0 to NA=Not calculable due to insufficient progression events	184 days Interval 51.0 to NA=Not calculable due to insufficient progression events
Time to Neurological/Brain Metastases Progression 50th percentile	NA days Interval 119.0 to NA=Not calculable due to insufficient progression events	NA days Interval 60.0 to NA=Not calculable due to insufficient progression events	184 days Interval 184.0 to NA=Not calculable due to insufficient progression events
Time to Neurological/Brain Metastases Progression 75th percentile	NA days Interval 119.0 to NA=Not calculable due to insufficient progression events	NA days NA=Not calculable due to insufficient progression events	NA days Interval 184.0 to NA=Not calculable due to insufficient progression events

Adverse Events

Placebo for ABT-888 BID + TMZ QD

Serious events: 28 serious events

Other events: 112 other events

Deaths: 0 deaths

ABT-888 20 mg BID + TMZ QD

Serious events: 27 serious events

Other events: 116 other events

Deaths: 0 deaths

ABT-888 40 mg BID + TMZ QD

Serious events: 31 serious events

Other events: 113 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Information

AbbVie

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo for ABT-888 BID + TMZ QD n=113 participants at risk Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 20 mg BID + TMZ QD n=116 participants at risk ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 participants at risk ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Blood and lymphatic system disorders ANAEMIA	1.8% 2/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders BONE MARROW FAILURE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	1.7% 2/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders LEUKOPENIA	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders LYMPHADENOPATHY	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders NEUTROPENIA	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders PANCYTOPENIA	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders THROMBOCYTOPENIA	3.5% 4/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.5% 4/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Cardiac disorders ANGINA PECTORIS	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Cardiac disorders ARRHYTHMIA	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	1.7% 2/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Cardiac disorders PERICARDIAL EFFUSION	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Endocrine disorders ADRENAL INSUFFICIENCY	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders ABDOMINAL PAIN	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders CONSTIPATION	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders GASTRIC HAEMORRHAGE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders HAEMATOCHEZIA	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders INTESTINAL OBSTRUCTION	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders MELAENA	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders MOUTH SWELLING	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders NAUSEA	1.8% 2/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders SMALL INTESTINAL HAEMORRHAGE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders VOMITING	1.8% 2/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	1.7% 2/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders DEATH	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders DISEASE PROGRESSION	1.8% 2/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders FATIGUE	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders PAIN	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders PYREXIA	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Hepatobiliary disorders CHOLANGITIS	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations APPENDICITIS	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations BRONCHITIS	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations CELLULITIS	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations LOCALISED INFECTION	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations PNEUMONIA	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations POST PROCEDURAL INFECTION	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.86% 1/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).

Other adverse events
Measure	Placebo for ABT-888 BID + TMZ QD n=113 participants at risk Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 20 mg BID + TMZ QD n=116 participants at risk ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.	ABT-888 40 mg BID + TMZ QD n=115 participants at risk ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days.
Musculoskeletal and connective tissue disorders ARTHRALGIA	11.5% 13/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	14.7% 17/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	12.2% 14/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders BACK PAIN	8.8% 10/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	18.1% 21/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	12.2% 14/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders GROIN PAIN	2.7% 3/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.4% 4/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders ANAEMIA	8.0% 9/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	16.4% 19/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	11.3% 13/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders LEUKOPENIA	4.4% 5/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.9% 8/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	7.0% 8/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders LYMPHOPENIA	4.4% 5/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.4% 4/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders NEUTROPENIA	6.2% 7/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	20.7% 24/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	22.6% 26/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Blood and lymphatic system disorders THROMBOCYTOPENIA	16.8% 19/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	42.2% 49/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	48.7% 56/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders ABDOMINAL PAIN	7.1% 8/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	9.5% 11/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	13.0% 15/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders ABDOMINAL PAIN UPPER	2.7% 3/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.4% 4/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders CONSTIPATION	54.9% 62/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	51.7% 60/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	53.9% 62/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders DIARRHOEA	21.2% 24/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	23.3% 27/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	22.6% 26/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders DRY MOUTH	5.3% 6/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders DYSPEPSIA	10.6% 12/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.9% 8/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	7.0% 8/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.00% 0/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	8.6% 10/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	1.7% 2/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders NAUSEA	66.4% 75/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	71.6% 83/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	71.3% 82/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Gastrointestinal disorders VOMITING	46.9% 53/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	36.2% 42/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	26.1% 30/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders CHEST PAIN	3.5% 4/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	4.3% 5/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders CHILLS	3.5% 4/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.9% 8/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	7.0% 8/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders FATIGUE	64.6% 73/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	64.7% 75/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	67.0% 77/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders INFLUENZA LIKE ILLNESS	3.5% 4/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders OEDEMA PERIPHERAL	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	7.8% 9/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.5% 4/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders PAIN	7.1% 8/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	8.6% 10/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	10.4% 12/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
General disorders PYREXIA	5.3% 6/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.0% 7/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.5% 4/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations SINUSITIS	4.4% 5/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.0% 7/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	6.2% 7/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.9% 8/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	8.7% 10/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Investigations HAEMOGLOBIN DECREASED	5.3% 6/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Investigations PLATELET COUNT DECREASED	3.5% 4/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	10.3% 12/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	8.7% 10/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Investigations WEIGHT DECREASED	6.2% 7/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.0% 7/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Metabolism and nutrition disorders DECREASED APPETITE	32.7% 37/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	22.4% 26/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	31.3% 36/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Metabolism and nutrition disorders HYPERGLYCAEMIA	5.3% 6/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.4% 4/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	4.3% 5/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	1.7% 2/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	5.3% 6/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	6.0% 7/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.87% 1/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	9.7% 11/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	9.5% 11/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	7.8% 9/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders MYALGIA	6.2% 7/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	3.4% 4/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	7.0% 8/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	9.7% 11/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	11.2% 13/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	8.7% 10/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CANCER PAIN	5.3% 6/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	0.00% 0/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR PAIN	0.88% 1/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	2.6% 3/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	5.2% 6/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Nervous system disorders DIZZINESS	15.0% 17/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	16.4% 19/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	13.0% 15/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).
Nervous system disorders DYSGEUSIA	7.1% 8/113 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	12.9% 15/116 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).	9.6% 11/115 • Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 5.6 years); SAEs were collected from the time informed consent was obtained (up to 5.7 years).