Trial Outcomes & Findings for Irritable Bowel Syndrome With Diarrhea (IBS-D) Rifaximin Re-Treatment Study (NCT NCT01543178)

Last Updated: 2017-12-12

Results Overview

Subjects who respond to repeat treatment in both IBS-related abdominal pain and stool consistency. The proportion of patients who responded to repeat treatment during the first double-blind repeat treatment phase is presented. Response is defined as improvement from baseline in abdominal pain AND reduction from baseline in diarrhea.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2583 participants

Primary outcome timeframe

4-week treatment-free follow-up in double-blind repeat treatment phase.

Results posted on

2017-12-12

Participant Flow

The screening phase included a 10 (±3) day run-in treatment period, during which subjects received single-blind placebo and completed a daily IBS symptom diary. Subjects who had active symptoms of IBS with diarrhea, and satisfied other entry criteria, entered the open-label period of study.

Participant milestones

Participant milestones
Measure	Open-label Rifaximin Subjects received open-label rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up. Responders continued into Maintenance Phase 1 (treatment free). Nonresponders withdrew from the study. Of the 2583 subjects in this group, 636 eventually met criteria for recurrence in Maintenance Phase 1, entered the double-blind period, and were randomized 1:1 to receive rifaximin 550 mg or placebo.	Double-blind Rifaximin (Retreatment) The 328 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the rifaximin group for the double-blind retreatment period. For participant flow during the open-label period, these subjects are included in the 2583 subjects in the open-label rifaximin group.	Double-blind Placebo (Retreatment) The 308 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the placebo group for the double-blind retreatment period. For participant flow during the open-label period, these subjects are included in the 2583 subjects in the open-label rifaximin group.
Open-label Period STARTED	2583	0	0
Open-label Period COMPLETED	636	0	0
Open-label Period NOT COMPLETED	1947	0	0
Double-blind Period STARTED	0	328	308
Double-blind Period COMPLETED	0	284	271
Double-blind Period NOT COMPLETED	0	44	37

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Irritable Bowel Syndrome With Diarrhea (IBS-D) Rifaximin Re-Treatment Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label Rifaximin Only n=1943 Participants The 1943 subjects in this group did not continue into the double-blind period of the study. Open-label treatment was rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up.	Double-blind Rifaximin (Retreatment) n=328 Participants The 328 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the rifaximin group for the double-blind retreatment period.	Double-blind Placebo (Retreatment) n=308 Participants The 308 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the placebo group for the double-blind retreatment period.	Total n=2579 Participants Total of all reporting groups
Age, Categorical <=18 years	8 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	9 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	1763 Participants n=99 Participants	289 Participants n=107 Participants	278 Participants n=206 Participants	2330 Participants n=7 Participants
Age, Categorical >=65 years	172 Participants n=99 Participants	39 Participants n=107 Participants	29 Participants n=206 Participants	240 Participants n=7 Participants
Age, Continuous	46.3 years STANDARD_DEVIATION 13.5 • n=99 Participants	47.9 years STANDARD_DEVIATION 14.2 • n=107 Participants	45.6 years STANDARD_DEVIATION 13.8 • n=206 Participants	46.4 years STANDARD_DEVIATION 13.7 • n=7 Participants
Sex: Female, Male Female	1319 Participants n=99 Participants	222 Participants n=107 Participants	219 Participants n=206 Participants	1760 Participants n=7 Participants
Sex: Female, Male Male	624 Participants n=99 Participants	106 Participants n=107 Participants	89 Participants n=206 Participants	819 Participants n=7 Participants

PRIMARY outcome

Timeframe: 4-week treatment-free follow-up in double-blind repeat treatment phase.

Population: Intent-to-treat population, defined as patients who received ≥ 1 dose of study drug in the double-blind period.

Outcome measures

Outcome measures
Measure	Double-blind Rifaximin (Retreatment) n=328 Participants The 328 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the rifaximin group for the double-blind retreatment period. During the double-blind period, subjects in this arm received rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with rifaximin.	Double-blind Placebo (Retreatment) n=308 Participants The 308 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the placebo group for the double-blind retreatment period. During the double-blind period, subjects in this arm received placebo TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with placebo.
Repeat Treatment Responders	32.6 percentage of patients	25.0 percentage of patients

Adverse Events

Total Open-label Experience

Serious events: 28 serious events

Other events: 198 other events

Deaths: 0 deaths

Double-blind Retreatment Experience - Rifaximin Group

Serious events: 4 serious events

Other events: 74 other events

Deaths: 0 deaths

Double-blind Retreatment Experience - Placebo Group

Serious events: 4 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Total Open-label Experience n=2579 participants at risk This group includes all 2579 subjects who received rifaximin the open-label period. Open-label experience is shown here.	Double-blind Retreatment Experience - Rifaximin Group n=328 participants at risk The 328 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the rifaximin group for the double-blind retreatment period. During the double-blind period, subjects in this arm received rifaximin 550 mg TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with rifaximin. Double-blind experience is shown here.	Double-blind Retreatment Experience - Placebo Group n=308 participants at risk The 308 subjects in this group received rifaximin in the open-label period, eventually met criteria for recurrence and were randomized to the placebo group for the double-blind retreatment period. During the double-blind period, subjects in this arm received placebo TID for 2 weeks with a 4-week treatment-free follow-up (first retreatment) followed by Maintenance Phase 2 (6 weeks \[treatment free\]) followed by a second retreatment with placebo. Double-blind experience is shown here.
Gastrointestinal disorders Diarrhoea	0.78% 20/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.1% 7/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	0.97% 3/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Gastrointestinal disorders Nausea	2.0% 52/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	3.7% 12/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.3% 7/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Gastrointestinal disorders Vomiting	0.93% 24/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	0.61% 2/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	1.6% 5/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Infections and infestations Bronchitis	0.58% 15/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.7% 9/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	1.6% 5/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Infections and infestations Nasopharyngitis	1.4% 36/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	3.0% 10/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.9% 9/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Infections and infestations Influenza	1.3% 33/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.1% 7/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	0.65% 2/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Infections and infestations Sinusitis	1.3% 34/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.1% 7/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.3% 7/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Infections and infestations Upper respiratory tract infection	1.6% 41/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	3.7% 12/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.6% 8/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Infections and infestations Urinary tract infection	1.4% 35/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	3.4% 11/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	4.9% 15/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Investigations Alanine aminotransferase increased	0.93% 24/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.7% 9/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	1.3% 4/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Investigations Aspartate aminotransferase increased	0.93% 24/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.1% 7/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	1.3% 4/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Investigations Blood creatine phosphokinase increased	1.2% 31/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.7% 9/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	0.97% 3/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.66% 17/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	0.91% 3/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.6% 8/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.
Nervous system disorders Headache	1.6% 42/2579 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	1.2% 4/328 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect adverse events.	2.9% 9/308 • Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period. The tables below present serious adverse events and other adverse events that were reported during treatment with study drug and during off-treatment follow-up and maintenance phases. Non-systematic (patient reports) and systematic methods (investigator examinations and laboratory tests) were used to collect 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