Trial Outcomes & Findings for Ability of Mayo Clinic High-performance Liquid Chromatography (HPLC) Method to Measure Fecal Bile Acids (NCT NCT02111603)

NCT ID: NCT02111603

Last Updated: 2016-05-12

Results Overview

Stool 48 hour collections (for BAs) were collected during baseline before treatment, and then during days 9-10 of the 10 days of colesevelam dosing for fecal BAs. Total fecal BA were measured using HPLC/tandem mass spectrometry.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 13 participants
• Primary outcome timeframe: baseline, 10 days
• Results posted on: 2016-05-12

Participant Flow

Participants were recruited from the Mayo Clinic in Rochester, Minnesota.

13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities.

Participant milestones

Measure	Colesevelam 1875 mg of Colesevelam orally twice daily for 10 days
Overall Study STARTED	13
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Colesevelam 1875 mg of Colesevelam orally twice daily for 10 days
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Ability of Mayo Clinic High-performance Liquid Chromatography (HPLC) Method to Measure Fecal Bile Acids

Baseline characteristics by cohort

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Age, Continuous	43.1 years STANDARD_DEVIATION 3.7 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants
Mean Body Mass Index (BMI)	31.1 kg/m^2 STANDARD_DEVIATION 2.4 • n=5 Participants

PRIMARY outcome

Timeframe: baseline, 10 days

Population: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.

Stool 48 hour collections (for BAs) were collected during baseline before treatment, and then during days 9-10 of the 10 days of colesevelam dosing for fecal BAs. Total fecal BA were measured using HPLC/tandem mass spectrometry.

Outcome measures

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam Baseline	1662 uM Standard Error 234.7
Change in Total 48 Hour Fecal Bile Acids (BA) From Baseline in Response to Treatment With Colesevelam After 10 days treatment with colesevelam	3496 uM Standard Error 709.2

SECONDARY outcome

Timeframe: baseline, 10 days

Population: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.

Change in fasting serum C4 from baseline in response to treatment with colesevelam.

Outcome measures

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Change in Fasting Serum C4 Baseline	24.7 ng/mL Standard Error 4.2
Change in Fasting Serum C4 After 10 days treatment with colesevelam	72.3 ng/mL Standard Error 12.2

SECONDARY outcome

Timeframe: baseline, 10 days

Population: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.

Change in fecal fat excretion from baseline in response to treatment with colesevelam

Outcome measures

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Change in Fecal Fat Excretion Baseline	6.4 g/day Standard Error 1.2
Change in Fecal Fat Excretion After 10 days treatment with colesevelam	6.8 g/day Standard Error 0.9

SECONDARY outcome

Timeframe: baseline, 10 days

Population: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.

The subjects rated their stool consistency using the Bristol Stool Form Scale. The Bristol Stool Form 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

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Change in Stool Consistency Baseline	4.8 units on a scale Standard Error 0.3
Change in Stool Consistency After 10 days treatment with colesevelam	4.4 units on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: baseline, 10 days

Population: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.

Change in stool frequency from baseline in response to treatment with colesevelam.

Outcome measures

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Change in Stool Frequency (Number of Stools Per Week) After 10 days treatment with colesevelam	15.1 Number of stools per week Standard Error 1.9
Change in Stool Frequency (Number of Stools Per Week) Baseline	17.6 Number of stools per week Standard Error 0.4

SECONDARY outcome

Timeframe: baseline, 10 days

Population: 13 subjects were accrued. One subject withdrew from the study after the pre-drug activities, but before the treatment activities. Only the 12 participants with complete data at both baseline and after 10 days of treatment are included in the Outcome Measure.

Stool 48 hour collections (for BAs) were collected during baseline before treatment, and then during days 9-10 of the 10 days of colesevelam dosing for fecal BAs. Relative composition of the main individual bile acids (cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA)) in 48 hour stool collection after colesevelam treatment were compared to baseline values.

The concordance correlation coefficient (rc) measures agreement between two variables. The concordance correlation satisfies -1 ≤ rc ≤ +1. A value of rc = +1 corresponds to perfect agreement. A value of rc = -1 corresponds to perfect negative agreement, and a value of rc = 0 corresponds to no agreement.

Outcome measures

Measure	Colesevelam n=12 Participants 1875 mg of Colesevelam orally twice daily for 10 days
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) LCA at Baseline	0.44 concordance correlation coefficient Standard Error 0.21
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) Total BAs at Baseline	0.53 concordance correlation coefficient Standard Error 0.13
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) Total BAs 48 hour collection after colesevelam	0.54 concordance correlation coefficient Standard Error 0.15
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) CA at Baseline	0.84 concordance correlation coefficient Standard Error 0.08
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) CA 48 hour collection after colesevelam	0.83 concordance correlation coefficient Standard Error 0.06
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) LCA 48 hour collection after colesevelam	0.88 concordance correlation coefficient Standard Error 0.07
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) DCA at Baseline	0.68 concordance correlation coefficient Standard Error 0.14
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) DCA 48 hour collection after colesevelam	0.85 concordance correlation coefficient Standard Error 0.07
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) UDCA at Baseline	0.96 concordance correlation coefficient Standard Error 0.20
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) UDCA 48 hour collection after colesevelam	0.54 concordance correlation coefficient Standard Error 0.20
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) CDCA at Baseline	0.88 concordance correlation coefficient Standard Error 0.05
Concordance Correlation Coefficients of the Relative Composition of Stool Total and the Main Individual Bile Acids (BA) CDCA 48 hour collection after colesevelam	0.90 concordance correlation coefficient Standard Error 0.06

Adverse Events

Colesevelam

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Colesevelam n=12 participants at risk 1875 mg of Colesevelam orally twice daily for 10 days
Gastrointestinal disorders Constipation	16.7% 2/12 • Number of events 2 • Participants were followed for adverse events for the 10 days they were on study.

Additional Information

Dr. Michael Camilleri

Mayo Clinic

Phone: 507-284-6218

Email: camilleri.michael@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place