Trial Outcomes & Findings for Rifaximin 3 Times/Day (TID) for Non-Constipation Irritable Bowel Syndrome (IBS) (NCT NCT00731679)

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

623 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	314	309
Overall Study COMPLETED	292	283
Overall Study NOT COMPLETED	22	26

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	7	8
Overall Study Withdrawal by Subject	8	8
Overall Study Lost to Follow-up	7	8
Overall Study Noncompliance	0	1
Overall Study Pregnancy	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=314 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=309 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=623 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	275 Participants n=99 Participants	274 Participants n=107 Participants	549 Participants n=206 Participants
Age, Categorical >=65 years	38 Participants n=99 Participants	34 Participants n=107 Participants	72 Participants n=206 Participants
Age, Continuous	45.5 years STANDARD_DEVIATION 14.6 • n=99 Participants	46.2 years STANDARD_DEVIATION 15.0 • n=107 Participants	45.8 years STANDARD_DEVIATION 14.8 • n=206 Participants
Sex: Female, Male Female	222 Participants n=99 Participants	235 Participants n=107 Participants	457 Participants n=206 Participants
Sex: Female, Male Male	92 Participants n=99 Participants	74 Participants n=107 Participants	166 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	30 Participants n=99 Participants	24 Participants n=107 Participants	54 Participants n=206 Participants
Race (NIH/OMB) White	280 Participants n=99 Participants	281 Participants n=107 Participants	561 Participants n=206 Participants
Race (NIH/OMB) More than one race	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 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.

Outcome measures

Outcome measures
Measure	Placebo n=314 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=309 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).	31.2 percentage of responders	40.8 percentage of responders

SECONDARY 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.

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=314 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=309 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).	28.7 percentage of responders	39.5 percentage of responders

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 101 other events

Deaths: 0 deaths

Rifaximin

Serious events: 3 serious events

Other events: 103 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=314 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=309 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 Rectal haemorrhage	0.32% 1/314 • 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% 0/309 • 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 Small intestinal obstruction	0.32% 1/314 • 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% 0/309 • 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.
Hepatobiliary disorders Cholecystitis	0.32% 1/314 • 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% 0/309 • 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.
Hepatobiliary disorders Cholecystitis acute	0.32% 1/314 • 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% 0/309 • 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 Gastroenteritis	0.32% 1/314 • 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% 0/309 • 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.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/314 • 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% 1/309 • 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 Costochondritis	0.00% 0/314 • 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% 1/309 • 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 Fracture nonunion	0.32% 1/314 • 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% 0/309 • 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 Amnesia	0.32% 1/314 • 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% 0/309 • 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 Alcohol withdrawal syndrome	0.00% 0/314 • 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% 1/309 • 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 Schizophrenia, paranoid type	0.32% 1/314 • 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% 0/309 • 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 Labile hypertension	0.32% 1/314 • 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% 0/309 • 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.

Other adverse events

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=314 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=309 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 distension	2.2% 7/314 • 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.	2.3% 7/309 • 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	7.3% 23/314 • 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.	6.1% 19/309 • 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	4.8% 15/314 • 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.	4.5% 14/309 • 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 Flatulence	3.5% 11/314 • 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.	1.9% 6/309 • 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	4.1% 13/314 • 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.	7.1% 22/309 • 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 Vomiting	2.5% 8/314 • 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.	3.6% 11/309 • 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	2.5% 8/314 • 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.	1.9% 6/309 • 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	5.7% 18/314 • 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.	2.3% 7/309 • 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	3.8% 12/314 • 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.	2.3% 7/309 • 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	2.9% 9/314 • 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.	2.6% 8/309 • 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 Urinary tract infection	1.9% 6/314 • 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.	2.3% 7/309 • 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	2.2% 7/314 • 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.	0.97% 3/309 • 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	5.1% 16/314 • 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.	5.8% 18/309 • 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 Cough	1.3% 4/314 • 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.	2.9% 9/309 • 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 Nasal congestion	0.32% 1/314 • 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.	2.3% 7/309 • 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 Pharyngolaryngeal pain	3.8% 12/314 • 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.	2.6% 8/309 • 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.