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Irritable Bowel Syndrome With Diarrhea (IBS-D) Rifaximin Re-Treatment Study (TARGET3)

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ClinicalTrials.gov Identifier: NCT01543178
Recruitment Status : Completed
First Posted : March 2, 2012
Results First Posted : July 8, 2015
Last Update Posted : December 12, 2017
Sponsor:
Information provided by (Responsible Party):
Valeant Pharmaceuticals International, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Irritable Bowel Syndrome With Diarrhea
Interventions Drug: open-label rifaximin
Drug: double-blind placebo
Drug: double-blind rifaximin
Enrollment 2583
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Open-label Rifaximin Double-blind Rifaximin (Retreatment) Double-blind Placebo (Retreatment)
Hide Arm/Group Description

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.

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. 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.
Period Title: Open-label Period
Started 2583 [1] 0 [2] 0 [3]
Completed 636 0 0
Not Completed 1947 0 0
[1]
2583 subjects entered the open-label period, but 4 received no rifaximin; 2579 received rifaximin.
[2]
The double-blind rifaximin arm/group is not applicable to the open-label period.
[3]
The double-blind placebo arm/group is not applicable to the open-label period.
Period Title: Double-blind Period
Started 0 [1] 328 [2] 308 [3]
Completed 0 284 [4] 271 [5]
Not Completed 0 44 37
[1]
The open-label rifaximin arm/group is not applicable to the double-blind period.
[2]
636 subjects had recurrence in open-label period; 328 randomized to rifaximin.
[3]
636 subjects had recurrence in open-label period; 308 randomized to placebo.
[4]
295 completed 1st double-blind retreatment and 284 completed 2nd double-blind retreatment.
[5]
283 completed 1st double-blind retreatment and 271 completed 2nd double-blind retreatment.
Arm/Group Title Open-label Rifaximin Only Double-blind Rifaximin (Retreatment) Double-blind Placebo (Retreatment) Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 1943 328 308 2579
Hide Baseline Analysis Population Description
Baseline results were summarized for the safety population, defined as patients who received at least 1 dose of study drug. Results are presented for patients in the open-label period only (1943) and for patients who eventually were randomized to rifaximin (329) or placebo (308) (ie, participated in both open-label and double-blind periods).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1943 participants 328 participants 308 participants 2579 participants
<=18 years
8
   0.4%
0
   0.0%
1
   0.3%
9
   0.3%
Between 18 and 65 years
1763
  90.7%
289
  88.1%
278
  90.3%
2330
  90.3%
>=65 years
172
   8.9%
39
  11.9%
29
   9.4%
240
   9.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1943 participants 328 participants 308 participants 2579 participants
46.3  (13.5) 47.9  (14.2) 45.6  (13.8) 46.4  (13.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1943 participants 328 participants 308 participants 2579 participants
Female
1319
  67.9%
222
  67.7%
219
  71.1%
1760
  68.2%
Male
624
  32.1%
106
  32.3%
89
  28.9%
819
  31.8%
1.Primary Outcome
Title Repeat Treatment Responders
Hide Description 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.
Time Frame 4-week treatment-free follow-up in double-blind repeat treatment phase.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, defined as patients who received ≥ 1 dose of study drug in the double-blind period.
Arm/Group Title Double-blind Rifaximin (Retreatment) Double-blind Placebo (Retreatment)
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 328 308
Measure Type: Number
Unit of Measure: percentage of patients
32.6 25.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind Rifaximin (Retreatment), Double-blind Placebo (Retreatment)
Comments A worst case analysis was performed, in which patients with < 4 days of IBS symptom data in a given week were considered as non-responders for that week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0232
Comments The a priori threshold for statistical significance was p < 0.05.
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel method was adjusted for analysis center and time to recurrence during Maintenance Phase 1.
Time Frame Up to 24 weeks for the open-label period. Up to 18 weeks for the double-blind period.
Adverse Event Reporting Description 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.
 
Arm/Group Title Total Open-label Experience Double-blind Retreatment Experience - Rifaximin Group Double-blind Retreatment Experience - Placebo Group
Hide Arm/Group Description

This group includes all 2579 subjects who received rifaximin the open-label period.

Open-label experience is shown here.

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.

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.

All-Cause Mortality
Total Open-label Experience Double-blind Retreatment Experience - Rifaximin Group Double-blind Retreatment Experience - Placebo Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Total Open-label Experience Double-blind Retreatment Experience - Rifaximin Group Double-blind Retreatment Experience - Placebo Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/2579 (1.09%)   4/328 (1.22%)   4/308 (1.30%) 
Blood and lymphatic system disorders       
Anaemia  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Cardiac disorders       
Coronary artery occlusion  1  0/2579 (0.00%)  0/328 (0.00%)  1/308 (0.32%) 
Gastrointestinal disorders       
Diverticulum  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Irritable bowel syndrome  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Rectal haemorrhage  1  2/2579 (0.08%)  0/328 (0.00%)  0/308 (0.00%) 
General disorders       
Non-cardiac chest pain  1  4/2579 (0.16%)  0/328 (0.00%)  1/308 (0.32%) 
Immune system disorders       
Hypersensitivity  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Infections and infestations       
Appendicitis  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Bronchitis viral  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Cellulitis  1  1/2579 (0.04%)  0/328 (0.00%)  1/308 (0.32%) 
Clostridium difficile colitis  1  0/2579 (0.00%)  1/328 (0.30%)  0/308 (0.00%) 
Groin abscess  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Pneumonia  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Postoperative wound infection  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  0/2579 (0.00%)  1/328 (0.30%)  0/308 (0.00%) 
Gun shot wound  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Humerus fracture  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Radius fracture  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Musculoskeletal and connective tissue disorders       
Bone cyst  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Intervertebral disc degeneration  1  2/2579 (0.08%)  0/328 (0.00%)  0/308 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Anal cancer  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Breast cancer  1  0/2579 (0.00%)  1/328 (0.30%)  0/308 (0.00%) 
Metastases to liver  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Uterine leiomyoma  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Nervous system disorders       
Convulsion  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Transient ischaemic attack  1  1/2579 (0.04%)  0/328 (0.00%)  2/308 (0.65%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Reproductive system and breast disorders       
Dysfunctional uterine bleeding  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Endometriosis  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Menorrhagia  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  0/2579 (0.00%)  1/328 (0.30%)  0/308 (0.00%) 
Pulmonary embolism  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Pulmonary hilum mass  1  1/2579 (0.04%)  0/328 (0.00%)  0/308 (0.00%) 
Vascular disorders       
Hypertension  1  1/2579 (0.04%)  0/328 (0.00%)  1/308 (0.32%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Total Open-label Experience Double-blind Retreatment Experience - Rifaximin Group Double-blind Retreatment Experience - Placebo Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   198/2579 (7.68%)   74/328 (22.56%)   69/308 (22.40%) 
Gastrointestinal disorders       
Diarrhoea  1  20/2579 (0.78%)  7/328 (2.13%)  3/308 (0.97%) 
Nausea  1  52/2579 (2.02%)  12/328 (3.66%)  7/308 (2.27%) 
Vomiting  1  24/2579 (0.93%)  2/328 (0.61%)  5/308 (1.62%) 
Infections and infestations       
Bronchitis  1  15/2579 (0.58%)  9/328 (2.74%)  5/308 (1.62%) 
Nasopharyngitis  1  36/2579 (1.40%)  10/328 (3.05%)  9/308 (2.92%) 
Influenza  1  33/2579 (1.28%)  7/328 (2.13%)  2/308 (0.65%) 
Sinusitis  1  34/2579 (1.32%)  7/328 (2.13%)  7/308 (2.27%) 
Upper respiratory tract infection  1  41/2579 (1.59%)  12/328 (3.66%)  8/308 (2.60%) 
Urinary tract infection  1  35/2579 (1.36%)  11/328 (3.35%)  15/308 (4.87%) 
Investigations       
Alanine aminotransferase increased  1  24/2579 (0.93%)  9/328 (2.74%)  4/308 (1.30%) 
Aspartate aminotransferase increased  1  24/2579 (0.93%)  7/328 (2.13%)  4/308 (1.30%) 
Blood creatine phosphokinase increased  1  31/2579 (1.20%)  9/328 (2.74%)  3/308 (0.97%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  17/2579 (0.66%)  3/328 (0.91%)  8/308 (2.60%) 
Nervous system disorders       
Headache  1  42/2579 (1.63%)  4/328 (1.22%)  9/308 (2.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: David Sorscher
Organization: Salix
Phone: 919-862-1827
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Valeant Pharmaceuticals International, Inc.
ClinicalTrials.gov Identifier: NCT01543178     History of Changes
Other Study ID Numbers: RFIB3053
First Submitted: February 27, 2012
First Posted: March 2, 2012
Results First Submitted: June 15, 2015
Results First Posted: July 8, 2015
Last Update Posted: December 12, 2017