Trial Outcomes & Findings for A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer (NCT NCT02407054)

Last Updated: 2021-05-11

Results Overview

PFS was defined as the time from randomization until the date of clinical (symptomatic or radiographic) and/or prostate specific antigen (PSA) disease progression per Prostate Cancer Clinical Trials Working Group (PCWG2) or death by any cause regardless of whether the participants withdraws from study drug or receives a subsequent anti-cancer therapy (as determined by the investigator). Participants who have not progressed or died at the time of assessment were censored at the time of the last date of assessment (tumor evaluation or PSA level).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

142 participants

Primary outcome timeframe

Randomization to Measured Progressive Disease or Death from Any Cause (Up To 34 Months)

Results posted on

2021-05-11

Participant Flow

Participants who did not voluntarily withdraw, or who were not removed from the study due to adverse event (AE), non-compliance, or at their physician's decision were considered to be study completers.

Participant milestones

Participant milestones
Measure	Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD Participants received 200 milligrams (mg) LY3023414 orally twice daily (BID) during initial week to assess pharmacokinetics (PK). Thereafter, participants received 200 mg of LY3023414 BID in combination with 160 mg of enzalutamide orally QD beginning Cycle 1 Day 1. A treatment cycle was defined as 28 days.	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD Participants received placebo in combination with 160 mg enzalutamide orally QD.
Overall Study STARTED	13	65	64
Overall Study Received at Least One Dose of Study Drug	13	65	64
Overall Study COMPLETED	6	47	57
Overall Study NOT COMPLETED	7	18	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD Participants received 200 milligrams (mg) LY3023414 orally twice daily (BID) during initial week to assess pharmacokinetics (PK). Thereafter, participants received 200 mg of LY3023414 BID in combination with 160 mg of enzalutamide orally QD beginning Cycle 1 Day 1. A treatment cycle was defined as 28 days.	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD Participants received placebo in combination with 160 mg enzalutamide orally QD.
Overall Study Adverse Event	1	4	1
Overall Study Non-compliance with Study	0	2	1
Overall Study Physician Decision	1	3	3
Overall Study Withdrawal by Subject	5	9	2

Baseline Characteristics

A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD n=13 Participants Participants received 200 mg LY3023414 orally every 12 hours (BID) during initial week to assess pharmacokinetics (PK). Thereafter, participants received 200 mg of LY3023414 BID in combination with 160 mg of enzalutamide orally QD beginning Cycle 1 Day 1. A treatment cycle was defined as 28 days.	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=65 Participants Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=64 Participants Participants received placebo in combination with 160 mg enzalutamide orally QD.	Total n=142 Participants Total of all reporting groups
Age, Continuous	74.4 years STANDARD_DEVIATION 8.43 • n=5 Participants	69.8 years STANDARD_DEVIATION 8.30 • n=7 Participants	70.9 years STANDARD_DEVIATION 9.07 • n=5 Participants	70.7 years STANDARD_DEVIATION 8.70 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	65 Participants n=7 Participants	64 Participants n=5 Participants	142 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	61 Participants n=7 Participants	63 Participants n=5 Participants	135 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	53 Participants n=7 Participants	55 Participants n=5 Participants	119 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment United States	13 Participants n=5 Participants	65 Participants n=7 Participants	64 Participants n=5 Participants	142 Participants n=4 Participants

PRIMARY outcome

Timeframe: Randomization to Measured Progressive Disease or Death from Any Cause (Up To 34 Months)

Population: All participants who received at least one dose of study drug in Part B. Per protocol, this analysis was planned for Part B only. Censored participants: Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD =19 and Part B: Placebo + 160 mg Enzalutamide QD =8.

Outcome measures

Outcome measures
Measure	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=46 Participants Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=56 Participants Participants received placebo in combination with 160 mg enzalutamide orally QD.
Part B: Progression Free Survival (PFS)	3.78 months Interval 2.89 to 5.06	2.83 months Interval 2.27 to 3.22

SECONDARY outcome

Timeframe: Randomization to Objective Disease Progression (Up To 34 Months)

Population: All participants who received at least one dose of study drug in Part B. Per protocol, this analysis was planned for Part B only. Censored participants: Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD=32 and Part B: Placebo + 160 mg Enzalutamide QD=22.

TTP was defined as time from randomization until the date of clinical (symptomatic or radiographic) and/or prostate specific antigen (PSA) disease progression per Prostate Cancer Clinical Trials Working Group (PCWG2).

Outcome measures

Outcome measures
Measure	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=33 Participants Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=42 Participants Participants received placebo in combination with 160 mg enzalutamide orally QD.
Part B: Time to Disease Progression (TTP)	5.06 months Interval 3.19 to 8.34	3.61 months Interval 2.86 to 4.7

SECONDARY outcome

Timeframe: 12 Weeks

Population: All participants who received at least one dose of study drug in Part B. Per protocol, this analysis was planned for Part B only.

PSA response was defined as more than 50% and 90% reduction from baseline to lowest post baseline value. 95% Confidence Intervals are based on Fisher's Exact Method.

Outcome measures

Outcome measures
Measure	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=65 Participants Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=64 Participants Participants received placebo in combination with 160 mg enzalutamide orally QD.
Part B: Percentage of Participants With Prostate Specific Antigen Response 50% PSA Response	21.5 Percentage of participants Interval 12.3 to 33.5	25.0 Percentage of participants Interval 15.0 to 37.4
Part B: Percentage of Participants With Prostate Specific Antigen Response 90% PSA Response	7.6 Percentage of participants Interval 2.5 to 17.0	9.3 Percentage of participants Interval 3.5 to 19.3

SECONDARY outcome

Timeframe: Part A: 200 mg LY3023414 + 160 mg Enzalutamide: Cycle 1 Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose

Population: All participants who received at least one dose of study drug and had evaluable PK data in Part A.

PK: Area under the Concentration-time Curve Over the Dosing Interval (AUCτ) of LY3023414 Time Frame: Part A LY3023414 200 mg: Day-1 pre-dose, 1.5, 3, and 6 hours post LY3023414 dose, Cycle 1 Day 1 pre-dose of LY3023414 and enzalutamide, and Part A Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose;

Outcome measures

Outcome measures
Measure	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=11 Participants Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=8 Participants Participants received placebo in combination with 160 mg enzalutamide orally QD.
Part A: Pharmacokinetic (PK): Area Under the Concentration-time Curve Over the Dosing Interval (AUCτ) of LY3023414	3230 nanogramhour/milliliter (ngh/mL) Geometric Coefficient of Variation 59	1820 nanogramhour/milliliter (ngh/mL) Geometric Coefficient of Variation 56

SECONDARY outcome

Timeframe: Randomization to Second Measured Complete Response or Partial Response (Up To 34 Months)

Population: All participants who received at least one dose of study drug in Part B. Per protocol, this analysis was planned for Part B only.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=65 Participants Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=64 Participants Participants received placebo in combination with 160 mg enzalutamide orally QD.
Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	4.6 percentage of participants Interval 1.0 to 12.9	4.6 percentage of participants Interval 1.0 to 13.1

Adverse Events

Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD

Serious events: 5 serious events

Other events: 13 other events

Deaths: 1 deaths

Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD

Serious events: 13 serious events

Other events: 64 other events

Deaths: 0 deaths

Part B: Placebo + 160 mg Enzalutamide QD

Serious events: 12 serious events

Other events: 63 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Part A: 200 mg LY3023414 BID + 160 mg of Enzalutamide QD n=13 participants at risk Participants received 200 mg LY3023414 orally every 12 hours (BID) during initial week to assess pharmacokinetics (PK). Thereafter, participants received 200 mg of LY3023414 BID in combination with 160 mg of enzalutamide orally QD beginning Cycle 1 Day 1. A treatment cycle was defined as 28 days.	Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD n=65 participants at risk Participants received 200 mg LY3023414 orally BID in combination with 160 mg enzalutamide orally once daily (QD).	Part B: Placebo + 160 mg Enzalutamide QD n=64 participants at risk Participants received placebo in combination with 160 mg enzalutamide orally QD.
Blood and lymphatic system disorders Anaemia	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Blood loss anaemia	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	3.1% 2/64 • Number of events 2 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Cardiac disorders Myocardial ischaemia	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	3.1% 2/64 • Number of events 2 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Diverticulum intestinal	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	3.1% 2/65 • Number of events 2 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
General disorders Chest pain	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Bacterial sepsis	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Cystitis	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	4.6% 3/65 • Number of events 3 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Pneumonia bacterial	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Postoperative wound infection	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Sepsis	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Tooth abscess	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Infections and infestations Viral infection	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Investigations Troponin i increased	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	3.1% 2/65 • Number of events 2 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Nervous system disorders Haemorrhage intracranial	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 2 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Renal and urinary disorders Haematuria	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/65 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	3.1% 2/64 • Number of events 2 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Renal and urinary disorders Urethral obstruction	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Renal and urinary disorders Urinary retention	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	7.7% 1/13 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/13 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	1.5% 1/65 • Number of events 1 • Baseline Up To 5 Years All participants who received at least one dose of study drug.	0.00% 0/64 • Baseline Up To 5 Years All participants who received at least one dose of study drug.