Trial Outcomes & Findings for Opioid-induced Bowel Dysfunction (OBD) Pivotal Assessment of Lubiprostone (OPAL) (NCT NCT01298219)

Last Updated: 2020-02-11

Results Overview

Spontaneous bowel movement (SBM) is defined as any BM that does not occur within 24 hours after use of rescue medication. To be classified as responders, participants are required to demonstrate at least moderate response (≥ 1 SBM improvement over baseline SBM frequency) for all treatment weeks for which observed data are available, and must additionally demonstrate a full response (≥ 3 SBMs per week) for at least 9 of the 12 treatment weeks.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

439 participants

Primary outcome timeframe

12 weeks

Results posted on

2020-02-11

Participant Flow

Recruitment period: 07 December 2010 to 16 November 2011 Recruitment sites: 91 U.S. investigative sites and 14 E.U. investigative sites

Safety evaluable population includes all subjects who were randomized and dosed. Intention to treat (ITT) population includes only those subjects who were dosed and provided at least one post-treatment efficacy assessment.

Participant milestones

Participant milestones
Measure	Lubiprostone 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Overall Study STARTED	219	220
Overall Study Intention to Treat (ITT)	219	220
Overall Study Safety Analysis Set	219	220
Overall Study COMPLETED	169	184
Overall Study NOT COMPLETED	50	36

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Opioid-induced Bowel Dysfunction (OBD) Pivotal Assessment of Lubiprostone (OPAL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lubiprostone n=219 Participants 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=220 Participants 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)	Total n=439 Participants Total of all reporting groups
Age, Continuous	51.9 years STANDARD_DEVIATION 9.01 • n=5 Participants	51.5 years STANDARD_DEVIATION 11.68 • n=7 Participants	51.7 years STANDARD_DEVIATION 10.42 • n=5 Participants
Sex: Female, Male Female	138 Participants n=5 Participants	138 Participants n=7 Participants	276 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	82 Participants n=7 Participants	163 Participants n=5 Participants
Region of Enrollment Czech Republic	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Belgium	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United States	202 participants n=5 Participants	203 participants n=7 Participants	405 participants n=5 Participants
Region of Enrollment Poland	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Germany	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Intention to treat

Outcome measures

Outcome measures
Measure	Lubiprostone n=219 Participants 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=220 Participants 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Number of Participants Classified as Treatment Responders Within 12 Weeks	59 Participants	41 Participants

SECONDARY outcome

Timeframe: at Week 8

Population: Intention to treat with data at Week 8

Outcome measures

Outcome measures
Measure	Lubiprostone n=168 Participants 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=182 Participants 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Number of SBMs Per Week at Week 8	2.9 SBMs/week Standard Deviation 3.18	2.5 SBMs/week Standard Deviation 3.03

SECONDARY outcome

Timeframe: within 48 hours post-dose

Population: Intention to treat

Outcome measures

Outcome measures
Measure	Lubiprostone n=219 Participants 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=220 Participants 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation within 24 Hours	110 Participants	84 Participants
Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation within 48 Hours	157 Participants	134 Participants

SECONDARY outcome

Timeframe: at Week 12

Population: Intention to treat with data at Week 12

Outcome measures

Outcome measures
Measure	Lubiprostone n=159 Participants 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=180 Participants 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Number of SBMs Per Week at Week 12	3.1 SBMs/week Standard Deviation 3.13	2.7 SBMs/week Standard Deviation 3.34

SECONDARY outcome

Timeframe: within 14 weeks

Population: Intention to treat with data at Week 14

Overall is defined as the length of time from first dose to last follow-up within 2 weeks after last dose.

Outcome measures

Outcome measures
Measure	Lubiprostone n=213 Participants 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=218 Participants 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Number of SBMs Per Week Overall	4.3 SBMs/week Standard Deviation 2.96	3.7 SBMs/week Standard Deviation 2.53

Adverse Events

Lubiprostone

Serious events: 7 serious events

Other events: 72 other events

Deaths: 1 deaths

Placebo

Serious events: 6 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Lubiprostone n=219 participants at risk 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=220 participants at risk 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Gastrointestinal disorders Diarrhea	11.0% 24/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	3.6% 8/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Nausea	9.6% 21/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	4.5% 10/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Vomiting	4.1% 9/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	5.0% 11/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Abdominal Pain	6.8% 15/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Flatulence	2.7% 6/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	2.3% 5/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Infections and infestations Urinary Tract Infection	3.2% 7/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	2.7% 6/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Infections and infestations Upper Respiratory Tract Infection	1.8% 4/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	2.3% 5/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Musculoskeletal and connective tissue disorders Back Pain	2.7% 6/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	2.3% 5/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Musculoskeletal and connective tissue disorders Arthralgia	2.3% 5/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	1.8% 4/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Investigations Gamma-Glutamyltransferase Increased	2.3% 5/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	1.8% 4/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.

Additional Information

Medical Information Call Center

Mallinckrodt Pharmaceuticals

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Lubiprostone n=219 participants at risk 24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	Placebo n=220 participants at risk 0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Gastrointestinal disorders Abdominal Pain	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Fecaloma	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Nausea	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Vomiting	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Injury, poisoning and procedural complications Ankle Fracture	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Injury, poisoning and procedural complications Contusion	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Injury, poisoning and procedural complications Drug Toxicity	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Musculoskeletal and connective tissue disorders Back Pain	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Nervous system disorders Syncope	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Nervous system disorders Migraine	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Cardiac disorders Coronary Artery Disease	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Renal and urinary disorders Nephrolithiasis	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Renal and urinary disorders Renal Failure Acute	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
General disorders Chest Pain	0.00% 0/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Investigations Hepatic Enzyme Increased	0.46% 1/219 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/220 • Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.