Trial Outcomes & Findings for Rifaximin 3 Times/Day (TID) for Non-Constipation Irritable Bowel Syndrome (IBS) (NCT NCT00724126)

Last Updated: 2019-11-29

Results Overview

The primary outcome measure is assessed during the 4-week period (ie, Weeks 3 through 6) immediately following 2 weeks of treatment with study drug. Adequate relief of global IBS symptoms was defined as a response of "yes" to the following question, which was asked weekly (every 7 days): "In regard to all your symptoms of IBS, as compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptoms? \[Yes/No\]"

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

637 participants

Primary outcome timeframe

4 weeks

Results posted on

2019-11-29

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.
Overall Study STARTED	321	316
Overall Study COMPLETED	302	301
Overall Study NOT COMPLETED	19	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	8	6
Overall Study Lost to Follow-up	6	6
Overall Study Noncompliance	2	1
Overall Study Subject randomized although ineligible	1	1
Overall Study Subject had to leave vicinity of site	0	1

Baseline Characteristics

Rifaximin 3 Times/Day (TID) for Non-Constipation Irritable Bowel Syndrome (IBS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=320 Participants Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin n=315 Participants Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Total n=635 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	282 Participants n=5 Participants	285 Participants n=7 Participants	567 Participants n=5 Participants
Age, Categorical >=65 years	37 Participants n=5 Participants	30 Participants n=7 Participants	67 Participants n=5 Participants
Age, Continuous	46.3 years STANDARD_DEVIATION 14.6 • n=5 Participants	45.9 years STANDARD_DEVIATION 13.9 • n=7 Participants	46.1 years STANDARD_DEVIATION 14.2 • n=5 Participants
Sex: Female, Male Female	225 Participants n=5 Participants	227 Participants n=7 Participants	452 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	88 Participants n=7 Participants	183 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	21 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) White	302 Participants n=5 Participants	282 Participants n=7 Participants	584 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: The analysis population was the intent-to-treat population, defined as subjects who received at least 1 dose of study drug. Two randomized subjects (1 in each group) did not receive study drug and were not included in the intent-to-treat population.

Outcome measures

Outcome measures
Measure	Placebo n=320 Participants Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin n=315 Participants Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.
Proportion of Subjects Who Had Adequate Relief of Global IBS Symptoms for at Least 2 of the 4 Weeks During the Primary Evaluation Period (ie, Weeks 3 Through 6).	32.2 percentage of responders	40.6 percentage of responders

SECONDARY outcome

Timeframe: 4 weeks

The secondary outcome measure is assessed during the 4-week period (ie, Weeks 3 through 6) immediately following 2 weeks of treatment with study drug. Adequate relief of bloating was defined as a response of "yes" to the following question, which was asked weekly (every 7 days): "In regard to your symptom of bloating, as compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptom of bloating? \[Yes/No\]."

Outcome measures

Outcome measures
Measure	Placebo n=320 Participants Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin n=315 Participants Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.
Proportion of Subjects Who Had Adequate Relief of IBS-related Bloating for at Least 2 of the 4 Weeks During the Primary Evaluation Period (ie, Weeks 3 Through 6)	31.9 percentage of responders	41.0 percentage of responders

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 94 other events

Deaths: 0 deaths

Rifaximin

Serious events: 7 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=320 participants at risk Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin n=315 participants at risk Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.
Gastrointestinal disorders Abdominal pain	3.4% 11/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.2% 10/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Constipation	2.5% 8/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Diarrhoea	2.2% 7/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	4.1% 13/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Nausea	3.4% 11/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	1.6% 5/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Infections and infestations Bronchitis	2.8% 9/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	2.2% 7/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Infections and infestations Nasopharyngitis	5.0% 16/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.8% 12/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Infections and infestations Sinusitis	1.2% 4/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.2% 10/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Infections and infestations Upper respiratory tract infection	9.4% 30/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	8.6% 27/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Musculoskeletal and connective tissue disorders Back pain	2.5% 8/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	2.2% 7/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Nervous system disorders Headache	8.1% 26/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	6.3% 20/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.

Additional Information

David Sorscher

Salix

Phone: 919-862-1827

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=320 participants at risk Subjects received placebo tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.	Rifaximin n=315 participants at risk Subjects received rifaximin 550 mg tablets 3 times daily for 2 weeks and were followed for 10 weeks after completion of the treatment period.
Infections and infestations Appendicitis	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Infections and infestations Meningitis	0.00% 0/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Cardiac disorders Atrial fibrillation	0.00% 0/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
General disorders Chest pain	0.62% 2/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
General disorders Non-cardiac chest pain	0.00% 0/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Metabolism and nutrition disorders Metabolic acidosis	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Musculoskeletal and connective tissue disorders Intervertebral disc displacement	0.00% 0/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Musculoskeletal and connective tissue disorders Neck pain	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Musculoskeletal and connective tissue disorders Pain in extremity	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Nervous system disorders Hypoaesthesia	0.00% 0/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Psychiatric disorders Bipolar I disorder	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Psychiatric disorders Mental status changes	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Respiratory, thoracic and mediastinal disorders Asthma	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Vascular disorders Hypertension	0.00% 0/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.32% 1/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Abdominal pain	0.31% 1/320 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	0.00% 0/315 • 12 weeks. Adverse events were collected during the 2-week treatment period and during the 10-week follow-up period. Non-systematic (patient reports) and systematic methods (investigator examinations/laboratory tests) were used to collect adverse events. A subject reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.