Trial Outcomes & Findings for A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer (NCT NCT03414047)

NCT ID: NCT03414047

Last Updated: 2022-08-19

Results Overview

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 172 participants
• Primary outcome timeframe: Baseline through Disease Progression (Up to 6 months)
• Results posted on: 2022-08-19

Participant Flow

Completers included participants who died from any cause and participants who were alive and on study (either on study treatment or in long term follow-up) at study conclusion.

Only 169 participants were assigned to one of the 4 cohorts in this study. Data is not available for 3 participants who discontinued before the start of the treatment.

Participant milestones

Measure	Prexasertib Cohort 1 Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.	Prexasertib Cohort 3 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.
Overall Study STARTED	53	46	41	29
Overall Study Received at Least One Dose of Study Drug	53	46	41	29
Overall Study COMPLETED	51	46	38	27
Overall Study NOT COMPLETED	2	0	3	2

Reasons for withdrawal

Measure	Prexasertib Cohort 1 Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.	Prexasertib Cohort 3 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.
Overall Study Adverse Event	0	0	1	1
Overall Study Physician Decision	1	0	0	1
Overall Study Withdrawal by Subject	1	0	2	0

Baseline Characteristics

A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

Baseline characteristics by cohort

Measure	Prexasertib Cohort 1 n=53 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=46 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.	Prexasertib Cohort 3 n=41 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=29 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Total n=169 Participants Total of all reporting groups
Age, Continuous	61.3 Years STANDARD_DEVIATION 9.4 • n=5 Participants	62.3 Years STANDARD_DEVIATION 9.4 • n=7 Participants	59.5 Years STANDARD_DEVIATION 8.6 • n=5 Participants	59.0 Years STANDARD_DEVIATION 13.4 • n=4 Participants	60.8 Years STANDARD_DEVIATION 10.0 • n=21 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	46 Participants n=7 Participants	41 Participants n=5 Participants	29 Participants n=4 Participants	169 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	40 Participants n=7 Participants	39 Participants n=5 Participants	28 Participants n=4 Participants	155 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	8 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	21 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	36 Participants n=7 Participants	37 Participants n=5 Participants	25 Participants n=4 Participants	144 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment South Korea	4 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Region of Enrollment Belgium	4 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	8 Participants n=21 Participants
Region of Enrollment United States	6 Participants n=5 Participants	13 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants	32 Participants n=21 Participants
Region of Enrollment United Kingdom	6 Participants n=5 Participants	9 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	20 Participants n=21 Participants
Region of Enrollment Italy	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	23 Participants n=21 Participants
Region of Enrollment Israel	6 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	4 Participants n=4 Participants	20 Participants n=21 Participants
Region of Enrollment Australia	14 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	3 Participants n=4 Participants	34 Participants n=21 Participants
Region of Enrollment Spain	9 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	19 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline through Disease Progression (Up to 6 months)

Population: All randomized participants who received at least one dose of study drug.

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.

Outcome measures

Measure	Prexasertib Cohort 3 n=41 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=29 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=53 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=46 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR)	12.2 Percentage of Participants Interval 4.1 to 26.2	6.9 Percentage of Participants Interval 0.8 to 22.8	11.3 Percentage of Participants Interval 4.3 to 23.0	13.0 Percentage of Participants Interval 4.9 to 26.3

SECONDARY outcome

Timeframe: Cycle 1, Cycle 2, Cycle 4, Cycle 6 (Day 1 (End of prexasertib infusion (+15 min), 1-2 hours following end of prexasertib infusion), Cycle 2, day 1(Prior to start of prexasertib infusion)

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data. Cohort 1, 2, 3 and 4 received the same dose and were combined per protocol.

Pharmacokinetics(PK): Maximum Plasma Concentration of Prexasertib. The same dose was administered to Cohort 1, 2, 3 and 4 and were combined for analysis.

Outcome measures

Measure	Prexasertib Cohort 3 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=151 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib Cycle 1	—	—	668 nanograms per milliliter(ng/mL) Geometric Coefficient of Variation 50	—
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib Cycle 2	—	—	718 nanograms per milliliter(ng/mL) Geometric Coefficient of Variation 62	—
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib Cycle 4	—	—	678 nanograms per milliliter(ng/mL) Geometric Coefficient of Variation 61	—
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib Cycle 6	—	—	672 nanograms per milliliter(ng/mL) Geometric Coefficient of Variation 42	—

SECONDARY outcome

Timeframe: Baseline through Disease Progression (up to 6 months)

Population: All randomized participants who received at least one dose of study drug.

DCR is defined as the number of participants who achieve a best overall response of CR, PR or SD for ≥4 months as determined by per RECIST version 1.1. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.

Outcome measures

Measure	Prexasertib Cohort 3 n=41 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=29 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=53 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=46 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) for at Least 4 Months	31.7 Percentage of participants Interval 18.1 to 48.1	31.0 Percentage of participants Interval 15.3 to 50.8	45.3 Percentage of participants Interval 31.6 to 59.6	32.6 Percentage of participants Interval 19.5 to 48.0

SECONDARY outcome

Timeframe: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (up to 20 months)

Population: All randomized participants who received at least one dose of study drug and had CR or PR responses. Number of participants censored Cohort 1 = 0, Cohort 2 = 1, Cohort 3 = 0 and Cohort 4 = 0.

Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

Outcome measures

Measure	Prexasertib Cohort 3 n=5 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=2 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=6 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=5 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Duration of Response	5.55 Months Interval 3.65 to 9.36	5.31 Months Interval 5.06 to The upper 95% confidence interval was not achieved due to high censoring rate.	8.57 Months Interval 5.55 to The upper 95% confidence interval was not achieved due to high censoring rate.	3.84 Months Interval 2.79 to The upper 95% confidence interval was not achieved due to high censoring rate.

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All randomized participants who received at least one dose of study drug.

CA-125 response is defined as ≥50% reduction in CA-125 levels from a pretreatment sample. The response must be confirmed and maintained for ≥28 days according to GCIG criteria. Participants must have a pretreatment sample that is ≥2 times the upper limit of the reference range and obtained within 2 weeks before starting the treatment.

Outcome measures

Measure	Prexasertib Cohort 3 n=41 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=29 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=53 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=46 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline	17.1 Percentage of participants	37.9 Percentage of participants	39.6 Percentage of participants	34.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Disease Progression or Death from any Cause (Up to 22 months)

Population: All randomized participants who received at least one dose of study drug. Number of participants censored Cohort 1 = 6, Cohort 2 = 4, Cohort 3 = 4 and Cohort 4 = 4.

Progression-Free Survival (PFS) is defined as the time from the date of enrollment until the first occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of progressive disease (PD). Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

Outcome measures

Measure	Prexasertib Cohort 3 n=37 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=25 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=47 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=42 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Progression-Free Survival	3.58 Months Interval 1.87 to 3.91	3.71 Months Interval 1.77 to 4.7	3.91 Months Interval 3.68 to 5.68	3.71 Months Interval 3.12 to 4.7

SECONDARY outcome

Timeframe: Baseline to Date of Death from Any Cause (Up to 26 months)

Population: All randomized participants who received at least one dose of study drug and had overall survival data. Number of participants censored Cohort 1 = 18, Cohort 2 = 12, Cohort 3 = 12 and Cohort 4 = 4.

Overall survival (OS) is defined as the time from the date of enrollment until death from any cause. If the participant is alive, lost to follow-up or withdrawn from study at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.

Outcome measures

Measure	Prexasertib Cohort 3 n=29 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=25 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.	Prexasertib Cohort 1 n=35 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=34 Participants Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.
Overall Survival	11.14 Months Interval 7.23 to 16.43	8.18 Months Interval 6.18 to 11.93	13.04 Months Interval 7.46 to 19.25	14.32 Months Interval 11.76 to 16.46

Adverse Events

Prexasertib Cohort 1

Serious events: 23 serious events

Other events: 53 other events

Deaths: 2 deaths

Prexasertib Cohort 2

Serious events: 17 serious events

Other events: 44 other events

Deaths: 1 deaths

Prexasertib Cohort 3

Serious events: 19 serious events

Other events: 39 other events

Deaths: 1 deaths

Prexasertib Cohort 4

Serious events: 15 serious events

Other events: 28 other events

Deaths: 1 deaths

Serious adverse events

Measure	Prexasertib Cohort 1 n=53 participants at risk Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=46 participants at risk Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.	Prexasertib Cohort 3 n=41 participants at risk Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=29 participants at risk Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.
Blood and lymphatic system disorders Anaemia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Febrile neutropenia	9.4% 5/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	12.2% 5/41 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Leukopenia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Neutropenia	7.5% 4/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	9.8% 4/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Thrombocytopenia	5.7% 3/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Cardiac disorders Atrioventricular block	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Cardiac disorders Myocardial infarction	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Cardiac disorders Pericardial effusion	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Cardiac disorders Sinus tachycardia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Abdominal pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Ascites	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Colitis	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Constipation	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Diarrhoea	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Gastritis	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Intestinal obstruction	1.9% 1/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Large intestine perforation	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Nausea	1.9% 1/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Obstruction gastric	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Small intestinal obstruction	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Vomiting	1.9% 1/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	8.7% 4/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.3% 3/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Asthenia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Chills	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Death	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Generalised oedema	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Hyperpyrexia	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Non-cardiac chest pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Obstruction	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Peripheral swelling	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Pyrexia	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Hepatobiliary disorders Biliary dilatation	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Diverticulitis	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Escherichia urinary tract infection	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Gastroenteritis viral	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Localised infection	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Neutropenic sepsis	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Pneumonia	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Sepsis	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Septic shock	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Soft tissue infection	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Tonsillitis	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Urinary tract infection	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Urosepsis	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Viral infection	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Wound infection	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Injury, poisoning and procedural complications Fall	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Blood creatinine increased	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Neutrophil count decreased	1.9% 1/53 • Number of events 11 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Platelet count decreased	1.9% 1/53 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Troponin increased	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations White blood cell count increased	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Decreased appetite	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Dehydration	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Nervous system disorders Encephalopathy	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Product Issues Device dislocation	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Renal and urinary disorders Acute kidney injury	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Renal and urinary disorders Pollakiuria	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Renal and urinary disorders Urinary tract obstruction	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Vascular disorders Hypertension	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Vascular disorders Peripheral artery thrombosis	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.

Other adverse events

Measure	Prexasertib Cohort 1 n=53 participants at risk Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.	Prexasertib Cohort 2 n=46 participants at risk Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.	Prexasertib Cohort 3 n=41 participants at risk Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.	Prexasertib Cohort 4 n=29 participants at risk Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.
Blood and lymphatic system disorders Anaemia	37.7% 20/53 • Number of events 64 • Baseline, upto 26 Months All randomized participants who received at least one dose.	37.0% 17/46 • Number of events 38 • Baseline, upto 26 Months All randomized participants who received at least one dose.	36.6% 15/41 • Number of events 40 • Baseline, upto 26 Months All randomized participants who received at least one dose.	41.4% 12/29 • Number of events 26 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.3% 3/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Leukopenia	7.5% 4/53 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	14.6% 6/41 • Number of events 10 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Neutropenia	35.8% 19/53 • Number of events 40 • Baseline, upto 26 Months All randomized participants who received at least one dose.	21.7% 10/46 • Number of events 26 • Baseline, upto 26 Months All randomized participants who received at least one dose.	26.8% 11/41 • Number of events 24 • Baseline, upto 26 Months All randomized participants who received at least one dose.	34.5% 10/29 • Number of events 15 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Blood and lymphatic system disorders Thrombocytopenia	32.1% 17/53 • Number of events 83 • Baseline, upto 26 Months All randomized participants who received at least one dose.	30.4% 14/46 • Number of events 36 • Baseline, upto 26 Months All randomized participants who received at least one dose.	34.1% 14/41 • Number of events 34 • Baseline, upto 26 Months All randomized participants who received at least one dose.	24.1% 7/29 • Number of events 18 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Abdominal discomfort	5.7% 3/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Abdominal distension	7.5% 4/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.2% 5/29 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Abdominal pain	26.4% 14/53 • Number of events 18 • Baseline, upto 26 Months All randomized participants who received at least one dose.	39.1% 18/46 • Number of events 40 • Baseline, upto 26 Months All randomized participants who received at least one dose.	26.8% 11/41 • Number of events 15 • Baseline, upto 26 Months All randomized participants who received at least one dose.	34.5% 10/29 • Number of events 14 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Abdominal pain lower	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Abdominal pain upper	5.7% 3/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	8.7% 4/46 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Ascites	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 11 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Constipation	24.5% 13/53 • Number of events 19 • Baseline, upto 26 Months All randomized participants who received at least one dose.	26.1% 12/46 • Number of events 15 • Baseline, upto 26 Months All randomized participants who received at least one dose.	19.5% 8/41 • Number of events 13 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.2% 5/29 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Diarrhoea	35.8% 19/53 • Number of events 57 • Baseline, upto 26 Months All randomized participants who received at least one dose.	32.6% 15/46 • Number of events 19 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.1% 7/41 • Number of events 11 • Baseline, upto 26 Months All randomized participants who received at least one dose.	27.6% 8/29 • Number of events 20 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Dry mouth	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Dyspepsia	5.7% 3/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	9.8% 4/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Mouth ulceration	5.7% 3/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Nausea	35.8% 19/53 • Number of events 54 • Baseline, upto 26 Months All randomized participants who received at least one dose.	52.2% 24/46 • Number of events 56 • Baseline, upto 26 Months All randomized participants who received at least one dose.	36.6% 15/41 • Number of events 33 • Baseline, upto 26 Months All randomized participants who received at least one dose.	55.2% 16/29 • Number of events 25 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Small intestinal obstruction	5.7% 3/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Gastrointestinal disorders Vomiting	39.6% 21/53 • Number of events 29 • Baseline, upto 26 Months All randomized participants who received at least one dose.	28.3% 13/46 • Number of events 20 • Baseline, upto 26 Months All randomized participants who received at least one dose.	26.8% 11/41 • Number of events 36 • Baseline, upto 26 Months All randomized participants who received at least one dose.	48.3% 14/29 • Number of events 25 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Asthenia	15.1% 8/53 • Number of events 19 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.4% 8/46 • Number of events 16 • Baseline, upto 26 Months All randomized participants who received at least one dose.	24.4% 10/41 • Number of events 38 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 13 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Catheter site pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Fatigue	39.6% 21/53 • Number of events 84 • Baseline, upto 26 Months All randomized participants who received at least one dose.	41.3% 19/46 • Number of events 37 • Baseline, upto 26 Months All randomized participants who received at least one dose.	29.3% 12/41 • Number of events 17 • Baseline, upto 26 Months All randomized participants who received at least one dose.	41.4% 12/29 • Number of events 20 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Mucosal inflammation	9.4% 5/53 • Number of events 8 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Non-cardiac chest pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Oedema peripheral	7.5% 4/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Pain	7.5% 4/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	12.2% 5/41 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.3% 3/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
General disorders Pyrexia	24.5% 13/53 • Number of events 17 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.1% 7/41 • Number of events 16 • Baseline, upto 26 Months All randomized participants who received at least one dose.	27.6% 8/29 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Cellulitis	5.7% 3/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Nasopharyngitis	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Upper respiratory tract infection	13.2% 7/53 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Urinary tract infection	7.5% 4/53 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Infections and infestations Viral infection	5.7% 3/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Injury, poisoning and procedural complications Fall	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Injury, poisoning and procedural complications Infusion related reaction	9.4% 5/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.0% 6/46 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.	9.8% 4/41 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Alanine aminotransferase increased	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Aspartate aminotransferase increased	3.8% 2/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Blood alkaline phosphatase increased	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Blood creatinine increased	5.7% 3/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Neutrophil count decreased	3.8% 2/53 • Number of events 11 • Baseline, upto 26 Months All randomized participants who received at least one dose.	19.6% 9/46 • Number of events 13 • Baseline, upto 26 Months All randomized participants who received at least one dose.	12.2% 5/41 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Platelet count decreased	15.1% 8/53 • Number of events 37 • Baseline, upto 26 Months All randomized participants who received at least one dose.	15.2% 7/46 • Number of events 17 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.1% 7/41 • Number of events 28 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.3% 3/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations Weight decreased	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Investigations White blood cell count decreased	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Decreased appetite	22.6% 12/53 • Number of events 14 • Baseline, upto 26 Months All randomized participants who received at least one dose.	26.1% 12/46 • Number of events 21 • Baseline, upto 26 Months All randomized participants who received at least one dose.	22.0% 9/41 • Number of events 12 • Baseline, upto 26 Months All randomized participants who received at least one dose.	24.1% 7/29 • Number of events 8 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Dehydration	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Hypokalaemia	5.7% 3/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 11 • Baseline, upto 26 Months All randomized participants who received at least one dose.	12.2% 5/41 • Number of events 10 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Hypomagnesaemia	3.8% 2/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 12 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Metabolism and nutrition disorders Hyponatraemia	7.5% 4/53 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Arthralgia	15.1% 8/53 • Number of events 11 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Back pain	20.8% 11/53 • Number of events 13 • Baseline, upto 26 Months All randomized participants who received at least one dose.	17.4% 8/46 • Number of events 14 • Baseline, upto 26 Months All randomized participants who received at least one dose.	14.6% 6/41 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.	20.7% 6/29 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Bone pain	5.7% 3/53 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.3% 3/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Muscle spasms	5.7% 3/53 • Number of events 13 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Musculoskeletal and connective tissue disorders Myalgia	1.9% 1/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Nervous system disorders Dizziness	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 8 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.4% 1/41 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Nervous system disorders Headache	15.1% 8/53 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.	21.7% 10/46 • Number of events 21 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Nervous system disorders Neuropathy peripheral	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Psychiatric disorders Anxiety	3.8% 2/53 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Psychiatric disorders Insomnia	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Renal and urinary disorders Pollakiuria	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Reproductive system and breast disorders Pelvic pain	5.7% 3/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 5/53 • Number of events 8 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	9.8% 4/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.3% 6/53 • Number of events 10 • Baseline, upto 26 Months All randomized participants who received at least one dose.	15.2% 7/46 • Number of events 8 • Baseline, upto 26 Months All randomized participants who received at least one dose.	9.8% 4/41 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	13.8% 4/29 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.4% 5/53 • Number of events 6 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/46 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/41 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Skin and subcutaneous tissue disorders Pruritus	9.4% 5/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.5% 3/46 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Skin and subcutaneous tissue disorders Rash	5.7% 3/53 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	10.9% 5/46 • Number of events 9 • Baseline, upto 26 Months All randomized participants who received at least one dose.	14.6% 6/41 • Number of events 7 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Vascular disorders Flushing	1.9% 1/53 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.9% 2/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	6.9% 2/29 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Vascular disorders Hot flush	0.00% 0/53 • Baseline, upto 26 Months All randomized participants who received at least one dose.	2.2% 1/46 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 3 • Baseline, upto 26 Months All randomized participants who received at least one dose.	0.00% 0/29 • Baseline, upto 26 Months All randomized participants who received at least one dose.
Vascular disorders Hypertension	9.4% 5/53 • Number of events 5 • Baseline, upto 26 Months All randomized participants who received at least one dose.	4.3% 2/46 • Number of events 2 • Baseline, upto 26 Months All randomized participants who received at least one dose.	7.3% 3/41 • Number of events 4 • Baseline, upto 26 Months All randomized participants who received at least one dose.	3.4% 1/29 • Number of events 1 • Baseline, upto 26 Months All randomized participants who received at least one dose.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

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

Restriction type: GT60