Trial Outcomes & Findings for Does Welchol (Colesevelam Hydrochloride) Improve Colonic Transit in Diarrhea-predominant Irritable Bowel Syndrome (D-IBS)? (NCT NCT00911612)

Results Overview

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

After 12-14 days treatment

Results posted on

2012-04-04

Participant Flow

All participants were recruited from the Mayo Clinic in Rochester, Minnesota from January through May 2009. 31 subjects signed consent, 1 withdrew consent before the start of the study, 2 had concomitant illness and 4 did not qualify based on colon transit eligibility criteria. 24 subjects were randomized and were included in the analysis.

Participant milestones

Participant milestones
Measure	Colesevelam Participants received colesevelam 1.875 g twice daily	Placebo Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Overall Study STARTED	12	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Does Welchol (Colesevelam Hydrochloride) Improve Colonic Transit in Diarrhea-predominant Irritable Bowel Syndrome (D-IBS)?

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Colesevelam n=12 Participants Participants received colesevelam 1.875 g twice daily	Placebo n=12 Participants Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy	Total n=24 Participants Total of all reporting groups
Age Continuous	42.1 years STANDARD_DEVIATION 4.0 • n=5 Participants	43.3 years STANDARD_DEVIATION 3.7 • n=7 Participants	42.8 years STANDARD_DEVIATION 13.0 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Body Mass Index	31.8 kg/m^2 STANDARD_DEVIATION 1.5 • n=5 Participants	28.9 kg/m^2 STANDARD_DEVIATION 1.8 • n=7 Participants	30.4 kg/m^2 STANDARD_DEVIATION 5.7 • n=5 Participants
Baseline Colonic Geometric Center at 24 hours	3.4 units on a scale STANDARD_DEVIATION 0.3 • n=5 Participants	3.4 units on a scale STANDARD_DEVIATION 0.3 • n=7 Participants	3.4 units on a scale STANDARD_DEVIATION 0.2 • n=5 Participants
Fasting Serum 7 alpha-HCO	31.8 ng/mL STANDARD_DEVIATION 5.9 • n=5 Participants	38.2 ng/mL STANDARD_DEVIATION 14.7 • n=7 Participants	35.0 ng/mL STANDARD_DEVIATION 36.5 • n=5 Participants

PRIMARY outcome

Timeframe: After 12-14 days treatment

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Outcome measures

Outcome measures
Measure	Colesevelam n=12 Participants Participants received colesevelam 1.875 g twice daily	Placebo n=12 Participants Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Colonic Transit, Geometric Center at 24 Hours	2.68 units on a scale Standard Error 0.32	3.30 units on a scale Standard Error 0.33

PRIMARY outcome

Timeframe: After 12-14 days' treatment

The half time for the ascending colon emptying (T1/2) was measured by the scintigraphic method. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule that is swallowed by the subject. Anterior and posterior gamma images are taken hourly. From the hourly scans, a time-activity curve is plotted using linear interpolation between time points when content was measured. The time taken to empty 50% of the isotope from the ascending colon is read from this time-activity curve.

Outcome measures

Outcome measures
Measure	Colesevelam n=12 Participants Participants received colesevelam 1.875 g twice daily	Placebo n=12 Participants Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Ascending Colon Emptying T1/2	18.85 hours Standard Error 2.88	14.9 hours Standard Error 3.58

SECONDARY outcome

Timeframe: after 12-14 days' treatment

Colonic permeability is measured through differential excretion of urine saccharides. The subject ingests a methacrylate-coated capsule that contains saccharides (mannitol 1g and lactulose 5 g powder). The capsule provides a means to protect the sugars from absorption, until the sugars are delivered to the colon by means of a standard delayed release capsule. The value reported is the mean for each arm of the total amount of mannitol excreted over the 8-24 hour time period.

Outcome measures

Outcome measures
Measure	Colesevelam n=12 Participants Participants received colesevelam 1.875 g twice daily	Placebo n=12 Participants Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Colonic Permeability as Measured by Cumulative Urinary Excretion of Mannitol 8-24 Hours	64.3 mg Standard Error 13.3	45.8 mg Standard Error 8.8

SECONDARY outcome

Timeframe: After 12-14 days' treatment

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Outcome measures

Outcome measures
Measure	Colesevelam n=12 Participants Participants received colesevelam 1.875 g twice daily	Placebo n=12 Participants Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Colonic Transit, Geometric Center at 48 Hours	4.65 units on a scale Standard Error 0.13	4.47 units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: After 12-14 days' treatment

The subjects rated their stool consistency using the Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.

Outcome measures

Outcome measures
Measure	Colesevelam n=12 Participants Participants received colesevelam 1.875 g twice daily	Placebo n=12 Participants Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Stool Consistency	3.78 units on a scale Standard Error 0.27	4.57 units on a scale Standard Error 0.35

Adverse Events

Colesevelam

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Colesevelam n=12 participants at risk Participants received colesevelam 1.875 g twice daily	Placebo n=12 participants at risk Participants received an inert capsule matching the study drug twice daily, as prepared by the Mayo Clinic research pharmacy
Reproductive system and breast disorders Uterine cramps	8.3% 1/12 • Number of events 1 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	16.7% 2/12 • Number of events 2 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.
Nervous system disorders Headache	41.7% 5/12 • Number of events 5 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	33.3% 4/12 • Number of events 4 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	8.3% 1/12 • Number of events 1 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	33.3% 4/12 • Number of events 4 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.
Gastrointestinal disorders Lower abdominal cramps	16.7% 2/12 • Number of events 2 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	0.00% 0/12 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.
Gastrointestinal disorders Flatulence	25.0% 3/12 • Number of events 3 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	8.3% 1/12 • Number of events 1 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.
Gastrointestinal disorders Green-colored stools	16.7% 2/12 • Number of events 2 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	16.7% 2/12 • Number of events 2 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.
Gastrointestinal disorders Nausea	16.7% 2/12 • Number of events 2 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.	25.0% 3/12 • Number of events 3 • Adverse events were collected from randomization through the 12-14 day treatment period (colesevelam HCL or placebo) and the 2 day testing period.

Additional Information

Dr. Michael Camilleri

Mayo Clinic

Phone: 507-266-2306

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place