Trial Outcomes & Findings for Lubiprostone in Children With Functional Constipation (NCT NCT02042183)

NCT ID: NCT02042183

Last Updated: 2020-07-21

Results Overview

An overall responder is defined as a participant who qualified as a weekly responder for 9 of the 12 treatment weeks, with durability demonstrated by at least 3 of the responder weeks occurring during the last 4 weeks of the treatment period. A weekly responder is defined as a participant who has at least 3 spontaneous bowel movements during the week, and at least one more than at baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

606 participants

Primary outcome timeframe

at Week 12

Results posted on

2020-07-21

Participant Flow

The two weeks between screening and treatment were used as a washout period for disallowed medications.

Participant milestones

Participant milestones
Measure	Lubiprostone Participants receive lubiprostone twice daily (BID)	Placebo Participants receive placebo BID up to 12 weeks
Overall Study STARTED	404	202
Overall Study Safety Population	400	195
Overall Study Modified Intent-to-treat (mITT)	399	195
Overall Study COMPLETED	339	166
Overall Study NOT COMPLETED	65	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Lubiprostone Participants receive lubiprostone twice daily (BID)	Placebo Participants receive placebo BID up to 12 weeks
Overall Study Physician Decision	7	2
Overall Study Lack of Efficacy	4	3
Overall Study Non-compliance with Study Drug	2	3
Overall Study Adverse Event	17	6
Overall Study Other	3	3
Overall Study Withdrawal by Subject	21	16
Overall Study Site Terminated by Sponsor	2	1
Overall Study Lost to Follow-up	9	2

Baseline Characteristics

The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: at Week 12

Population: mITT population

Outcome measures

Outcome measures
Measure	Lubiprostone n=399 Participants Participants receive lubiprostone BID for up to 12 weeks	Placebo n=195 Participants Participants receive placebo BID for up to 12 weeks.
Number of Participants Classified as Overall Responders at Week 12	76 Participants	28 Participants

SECONDARY outcome

Timeframe: within 12 Weeks

Population: mITT

Data provided is based on observed cases. Baseline is the average of the 2 weeks before being randomized. Participants are summarized by actual dose received after week 1.

Outcome measures

Outcome measures
Measure	Lubiprostone n=399 Participants Participants receive lubiprostone BID for up to 12 weeks	Placebo n=195 Participants Participants receive placebo BID for up to 12 weeks.
Mean Number of SBMs Observed Each Week for 12 Weeks at Baseline	1.40 Spontaneous bowel movements Standard Deviation 0.836	1.42 Spontaneous bowel movements Standard Deviation 0.855
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 1	2.65 Spontaneous bowel movements Standard Deviation 2.137	2.50 Spontaneous bowel movements Standard Deviation 2.117
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 2	2.68 Spontaneous bowel movements Standard Deviation 2.422	2.69 Spontaneous bowel movements Standard Deviation 2.328
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 3	2.85 Spontaneous bowel movements Standard Deviation 2.446	2.59 Spontaneous bowel movements Standard Deviation 2.435
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 4	2.94 Spontaneous bowel movements Standard Deviation 2.531	2.69 Spontaneous bowel movements Standard Deviation 2.499
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 5	2.91 Spontaneous bowel movements Standard Deviation 2.498	2.68 Spontaneous bowel movements Standard Deviation 2.495
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 6	2.91 Spontaneous bowel movements Standard Deviation 2.454	2.65 Spontaneous bowel movements Standard Deviation 2.163
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 7	2.81 Spontaneous bowel movements Standard Deviation 2.483	2.75 Spontaneous bowel movements Standard Deviation 2.704
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 8	2.94 Spontaneous bowel movements Standard Deviation 2.501	2.64 Spontaneous bowel movements Standard Deviation 2.444
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 9	2.83 Spontaneous bowel movements Standard Deviation 2.286	2.37 Spontaneous bowel movements Standard Deviation 1.875
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 10	2.68 Spontaneous bowel movements Standard Deviation 2.326	2.40 Spontaneous bowel movements Standard Deviation 2.103
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 11	2.78 Spontaneous bowel movements Standard Deviation 2.251	2.60 Spontaneous bowel movements Standard Deviation 2.362
Mean Number of SBMs Observed Each Week for 12 Weeks at Week 12	2.90 Spontaneous bowel movements Standard Deviation 2.497	2.75 Spontaneous bowel movements Standard Deviation 2.530

Adverse Events

Lubiprostone

Serious events: 11 serious events

Other events: 234 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lubiprostone n=400 participants at risk Participants receive lubiprostone BID for up to 12 weeks	Placebo n=195 participants at risk Participants received placebo BID for up to 12 weeks
Immune system disorders Anaphylactoid reaction	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.00% 0/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
General disorders Chest pain	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.00% 0/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Faecaloma	1.0% 4/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	1.0% 2/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Psychiatric disorders Suicidal ideation	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.51% 1/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Psychiatric disorders Major depression	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.00% 0/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Psychiatric disorders Hand-foot-and-mouth disease	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.00% 0/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Infections and infestations Cellulitis	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.00% 0/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Skin and subcutaneous tissue disorders Rash	0.25% 1/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.00% 0/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Constipation	0.00% 0/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	1.0% 2/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.51% 1/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Nervous system disorders Epilepsy	0.00% 0/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.51% 1/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Surgical and medical procedures Meniscus operation	0.00% 0/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	0.51% 1/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.

Other adverse events

Other adverse events
Measure	Lubiprostone n=400 participants at risk Participants receive lubiprostone BID for up to 12 weeks	Placebo n=195 participants at risk Participants received placebo BID for up to 12 weeks
Nervous system disorders Headache	8.5% 34/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	5.1% 10/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Nausea	14.2% 57/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	7.2% 14/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Vomiting	11.2% 45/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	6.2% 12/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Abdominal pain	10.5% 42/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	11.8% 23/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Diarrhoea	7.0% 28/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	3.1% 6/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Gastrointestinal disorders Abdominal pain upper	5.0% 20/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	3.1% 6/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.
Infections and infestations Pharyngitis streptococcal	2.0% 8/400 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.	5.6% 11/195 • Treatment emergent adverse events (TEAEs) in the safety population are reported for 14 weeks 1. Treatment-emergent adverse events are defined as any event with an onset date that is on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. 2. Participants are summarized in the dosing group assigned at randomization. The total number of participants in the 5% non-serious adverse event population was not provided, so the number affected is a total number of adverse events experienced by the 5% population.

Additional Information

Clinical Team Leader

Mallinckrodt Pharmaceuticals

Phone: 800-844-2830

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Lubiprostone n=404 Participants Participants receive lubiprostone BID up to 12 weeks	Placebo n=202 Participants Participants receive placebo BID up to 12 weeks	Total n=606 Participants Total of all reporting groups
Age, Customized 6-9 years	142 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	66 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	208 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Age, Customized 10-13 years	153 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	78 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	231 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Age, Customized 14-17 years	104 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	51 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	155 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Sex: Female, Male Female	216 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	106 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	322 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Sex: Female, Male Male	183 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	89 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	272 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Ethnicity (NIH/OMB) Hispanic or Latino	76 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	44 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	120 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Ethnicity (NIH/OMB) Not Hispanic or Latino	323 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	151 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	474 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	0 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	0 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	3 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	3 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) Asian	3 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	3 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	6 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	1 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	2 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) Black or African American	67 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	39 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	106 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) White	308 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	138 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	446 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) More than one race	0 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	0 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	0 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Race (NIH/OMB) Unknown or Not Reported	20 Participants n=399 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	11 Participants n=195 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.	31 Participants n=594 Participants • The modified intention-to-treat (mITT) population was used for reporting this baseline measure. The mITT population excluded participants from two sites that were terminated by the sponsor.
Region of Enrollment Canada	5 participants n=404 Participants	7 participants n=202 Participants	12 participants n=606 Participants
Region of Enrollment Netherlands	14 participants n=404 Participants	32 participants n=202 Participants	46 participants n=606 Participants
Region of Enrollment Belgium	1 participants n=404 Participants	3 participants n=202 Participants	4 participants n=606 Participants
Region of Enrollment United States	174 participants n=404 Participants	348 participants n=202 Participants	522 participants n=606 Participants
Region of Enrollment Poland	3 participants n=404 Participants	8 participants n=202 Participants	11 participants n=606 Participants
Region of Enrollment United Kingdom	4 participants n=404 Participants	6 participants n=202 Participants	10 participants n=606 Participants
Region of Enrollment France	1 participants n=404 Participants	0 participants n=202 Participants	1 participants n=606 Participants