Trial Outcomes & Findings for A Study of MD-7246 to Treat Abdominal Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome (NCT NCT03931785)

NCT ID: NCT03931785

Last Updated: 2021-03-12

Results Overview

Abdominal pain is measured daily in an eDiary, using an 11-point NRS, where 0 is anchored with "no abdominal pain" and 10 is anchored with "worst possible abdominal pain." The postbaseline weekly abdominal pain score is the average of the non-missing daily abdominal pain at its worst scores during a week (Weeks 1-12) if there are at least 4 daily scores entered into the eDiary during the week. Weekly change from baseline was calculated for each week as the weekly score minus the baseline score. Mixed model repeated measures (MMRM) results are based on a repeated measures analysis with treatment, analysis week, and treatment-by-week interaction as fixed effects and baseline as covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect. Baseline is derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 515 participants
• Primary outcome timeframe: Baseline, up to Week 12 (end of the Treatment Period)
• Results posted on: 2021-03-12

Participant Flow

This study included a Pretreatment Period, 14 to 21 days immediately before randomization. During this period, participants underwent symptomatic assessments in an electronic diary (eDiary); those who satisfied all entry criteria based on these assessments entered the Treatment Period and were randomized to 1 of 4 treatments: MD-7246 300, 600, or 1200 μg or placebo (1:1:1:1). Of the 515 participants in the Pretreatment Period, 127 were not randomized.

Participant milestones

Measure	Placebo 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg 4 MD-7246 300-μg oral tablets QD for 12 weeks
Overall Study STARTED	97	97	97	97
Overall Study COMPLETED	92	90	84	86
Overall Study NOT COMPLETED	5	7	13	11

Reasons for withdrawal

Measure	Placebo 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg 4 MD-7246 300-μg oral tablets QD for 12 weeks
Overall Study Lost to Follow-up	4	1	4	3
Overall Study Adverse Event	1	0	3	4
Overall Study Protocol Violation	0	1	0	0
Overall Study Noncompliance With Study drug	0	1	0	0
Overall Study Other Not specified	0	2	2	2
Overall Study Withdrawal by Subject	0	2	4	1
Overall Study Pregnancy	0	0	0	1

Baseline Characteristics

A Study of MD-7246 to Treat Abdominal Pain in Patients With Diarrhea-predominant Irritable Bowel Syndrome

Baseline characteristics by cohort

Measure	Placebo n=97 Participants 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg n=97 Participants 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg n=97 Participants 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg n=97 Participants 4 MD-7246 300-μg oral tablets QD for 12 weeks	Total n=388 Participants Total of all reporting groups
Age, Continuous	43.4 years STANDARD_DEVIATION 13.12 • n=5 Participants	45.0 years STANDARD_DEVIATION 14.04 • n=7 Participants	42.2 years STANDARD_DEVIATION 14.38 • n=5 Participants	45.1 years STANDARD_DEVIATION 14.58 • n=4 Participants	43.9 years STANDARD_DEVIATION 14.04 • n=21 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	63 Participants n=7 Participants	67 Participants n=5 Participants	68 Participants n=4 Participants	264 Participants n=21 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	34 Participants n=7 Participants	30 Participants n=5 Participants	29 Participants n=4 Participants	124 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	23 Participants n=7 Participants	29 Participants n=5 Participants	13 Participants n=4 Participants	89 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants	74 Participants n=7 Participants	68 Participants n=5 Participants	84 Participants n=4 Participants	299 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian	72 Participants n=5 Participants	69 Participants n=7 Participants	75 Participants n=5 Participants	67 Participants n=4 Participants	283 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	51 Participants n=21 Participants
Race/Ethnicity, Customized Asian	13 Participants n=5 Participants	14 Participants n=7 Participants	9 Participants n=5 Participants	14 Participants n=4 Participants	50 Participants n=21 Participants
Race/Ethnicity, Customized Multiple Races	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Abdominal Pain at Its Worst at Each Week on a Numerical Rating Scale (NRS)	6.22 units on a scale STANDARD_DEVIATION 1.236 • n=5 Participants	6.05 units on a scale STANDARD_DEVIATION 1.112 • n=7 Participants	5.95 units on a scale STANDARD_DEVIATION 1.129 • n=5 Participants	6.24 units on a scale STANDARD_DEVIATION 1.169 • n=4 Participants	6.12 units on a scale STANDARD_DEVIATION 1.164 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, up to Week 12 (end of the Treatment Period)

Population: Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at Baseline and during the treatment period.

Abdominal pain is measured daily in an eDiary, using an 11-point NRS, where 0 is anchored with "no abdominal pain" and 10 is anchored with "worst possible abdominal pain." The postbaseline weekly abdominal pain score is the average of the non-missing daily abdominal pain at its worst scores during a week (Weeks 1-12) if there are at least 4 daily scores entered into the eDiary during the week. Weekly change from baseline was calculated for each week as the weekly score minus the baseline score.

Mixed model repeated measures (MMRM) results are based on a repeated measures analysis with treatment, analysis week, and treatment-by-week interaction as fixed effects and baseline as covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.

Baseline is derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization.

Outcome measures

Measure	Placebo n=97 Participants 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg n=97 Participants 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg n=97 Participants 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg n=97 Participants 4 MD-7246 300-μg oral tablets QD for 12 weeks
Change From Baseline in Abdominal Pain at Its Worst on a NRS Through the Treatment Period	-2.01 units on a scale Standard Error 0.179	-1.93 units on a scale Standard Error 0.179	-1.58 units on a scale Standard Error 0.182	-1.95 units on a scale Standard Error 0.180

PRIMARY outcome

Timeframe: Baseline through Week 12

Population: Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at Baseline and during the treatment period.

A 6/12 Week Abdominal Pain 30% Responder was a participant who had a decrease from baseline of ≥30% in the weekly abdominal pain score for that week for at least 6 out of the 12 weeks of the Treatment Period; for any week, a participant with < 4 daily abdominal pain scores available was considered a non-responder for that week.

Abdominal pain is measured daily in an eDiary, using an 11-point NRS, where 0 is anchored with "no abdominal pain" and 10 is anchored with "worst possible abdominal pain." The postbaseline weekly abdominal pain score is the average of the non-missing daily abdominal pain at its worst scores during a week (Weeks 1-12) if there are at least 4 daily scores entered into the eDiary during the week.

Outcome measures

Measure	Placebo n=97 Participants 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg n=97 Participants 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg n=97 Participants 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg n=97 Participants 4 MD-7246 300-μg oral tablets QD for 12 weeks
Percentage of Participants Who Were 6/12 Week Abdominal Pain 30% Change Responders	55.7 percentage of participants	56.7 percentage of participants	44.3 percentage of participants	48.5 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

MD-7246 300 μg

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

MD-7246 600 μg

Serious events: 0 serious events

Other events: 42 other events

Deaths: 0 deaths

MD-7246 1200 μg

Serious events: 1 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=97 participants at risk 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg n=97 participants at risk 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg n=97 participants at risk 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg n=97 participants at risk 4 MD-7246 300-μg oral tablets QD for 12 weeks
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.

Other adverse events

Measure	Placebo n=97 participants at risk 4 matching placebo oral tablets once daily (QD) for 12 weeks	MD-7246 300 μg n=97 participants at risk 1 MD-7246 300-μg oral tablet and 3 matching placebo oral tablets QD for 12 weeks	MD-7246 600 μg n=97 participants at risk 2 MD-7246 300-μg oral tablets and 2 matching placebo oral tablets QD for 12 weeks	MD-7246 1200 μg n=97 participants at risk 4 MD-7246 300-μg oral tablets QD for 12 weeks
Infections and infestations Nasopharyngitis	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	5.2% 5/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	5.2% 5/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Nervous system disorders Headache	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Nausea	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Upper respiratory tract infection	7.2% 7/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	5.2% 5/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Influenza	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	5.2% 5/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Constipation	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Diarrhoea	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Sinusitis	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	4.1% 4/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Nervous system disorders Dizziness	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Urinary tract infection	3.1% 3/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Vulvovaginal mycotic infection	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Abdominal pain	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Bronchitis	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
General disorders Fatigue	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Vascular disorders Hypertension	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Psychiatric disorders Insomnia	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	1.0% 1/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Abdominal distension	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Infections and infestations Bacterial vaginosis	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Metabolism and nutrition disorders Dehydration	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.
Gastrointestinal disorders Vomiting	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	0.00% 0/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.	2.1% 2/97 • From the first dose of double-blind study drug and within 1 day of the date of last dose of double-blind study drug in the treatment period (up to Week 12 / Day 85). Mean treatment duration was 82.8, 77.3, and 80.8 days in the MD-7246 300, 600, and 1200 μg groups, respectively, and 83.3 days in the placebo group.

Additional Information

Wilmin Bartolini, Ph.D.

Ironwood Pharmaceuticals, Inc.

Phone: 617.621.8314

Email: wbartolini@ironwoodpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI may publish or disclose the results of the study 24 months after final data lock provided that sponsor can review the publication prior to public release, sponsor can request removal of confidential information of sponsor (not including results of trial), and sponsor can request a publication delay in order to protect potentially patentable information. Furthermore, if a publication committee is developing an initial publication, PI is to delay disclosure until that publication is published.
• Publication restrictions are in place

Restriction type: OTHER