Comparison of Colesevelam Hydrogen Chloride (HCl) Powder For Oral Suspension Versus Generic Cholestyramine Through Use of the Bile Acid Sequestrant Acceptability (BASA) Scale

• Sponsor: Louisville Metabolic and Atherosclerosis Research Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01122108
• Collaborator: Provident Clinical Research (Other), Daiichi Sankyo, Inc. (Industry)
• Enrollment: 42
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 21

Study Details

Study Description

Brief Summary

The objective of this study is to compare the acceptability of Colesevelam HCl powder for oral suspension versus generic cholestyramine via the BASA scale, based upon an anticipated equivalent cholesterol lowering doses of each comparator drug.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Cholestyramine; Drug: Colesevelam HCl	Phase 4

Detailed Description

In 2009, colesevelam HCl was approved as a powder formulation. Little objective evidence exists comparing the acceptability of colesevelam HCl powder for oral suspension formulation versus other bile acid sequestrant powder formulations. A Bile Acid Sequestrant Acceptability (BASA) Scale was developed and validated as an instrument to compare the acceptability of different bile acid sequestrant preparations

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized, Single-Blind, Single Research Site, Comparison of Colesevelam Hydrogen Chloride (HCl) Powder For Oral Suspension Versus Generic Cholestyramine Through Use of the Bile Acid Sequestrant Acceptability (BASA) Scale in Generally Healthy Subjects
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cholestyramine 12 grams Cholestyramine 12 grams	Drug: Cholestyramine; Cholestyramine 12 grams, one time dose; Other Names: Questran
Active Comparator: Colesevelam HCl Colesevelam HCl, 4 grams	Drug: Colesevelam HCl; Colesevelam HCl, 4 grams, one time dose; Other Names: Welchol

Outcome Measures

Primary Outcome Measures

1. Patient Acceptability of Colesevelam HCl Powder for Oral Suspension vs. Generic Cholestyramine Via the Bile Acid Sequestrant Acceptability (BASA) Scale, Based Upon an Anticipated Equivalent Cholesterol Lowering Doses of Each Comparator Drug. [1 Day]

   The bile acid sequestrant acceptability (BASA) scale has 4 scoring categories: taste, texture, appearance, and mixability. Participants rank each category separately. The best possible score for each category is 5, and the worst possible score for each category is 1.

Other Outcome Measures

1. Weighted vs. Unweighted Composite BASA Scale Scores [1 Day]

   Aggregate scores were calculated for both the unweighted and weighted BASA scale scores for both Colesevlam HCL (3.75G) and Cholestyramine (12g). The best possible total BASA score is 20 and the worst possible total BASA score is 4. For the weighted version of the scale, the best possible total score is 60 and the worst possible total score is 4.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Men or women 18-70 years of age

• In general good health (defined as study participants who are medically stable, meet protocol criteria, but who may also have non-exclusionary ongoing medical conditions).

• Subjects are capable of giving informed consent, or if appropriate, have an acceptable surrogate capable of giving consent on the subject's behalf.

• Subjects are willing and readily able to be contacted for post-study safety phone call assessments one to seven days after the single study visit.

Exclusion Criteria:

• Prior intolerance to bile acid sequestrants

• Known Phenylketonuria. Colesevelam (Welchol) for Oral Suspension contains 48 mg phenylalanine per 3.75 gram dose.

• Women who are either pregnant, or who are not practicing any form of birth control.

• Prior gastrointestinal surgery

• History of ongoing gastrointestinal symptoms (indigestion, constipation, or diarrhea)

• History of bowel obstruction, malabsorption, or irritable bowel syndrome

• History of esophageal disease

• Current or past history of gallbladder disease

• History of pancreatitis

• Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to visit 1.

• Diagnosis of diabetes mellitus

• Known history of triglyceride levels > 300 mg/dl.

• History of alcohol or drug abuse within 1 year of study entry

• Alcohol intake that exceeds more than 2 units of alcohol drinks per day

• Exposure to bile acid sequestrants (colesevelam HCl, cholestyramine, colestipol within 30 days of visit 1).

• Any other situation in which the Investigator makes the judgment that participation in the study would not be in the best interest of the study participant, or in the best interest of providing reliable study data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	L-MARC Research Center	Louisville	Kentucky	United States	40213

Sponsors and Collaborators

• Louisville Metabolic and Atherosclerosis Research Center
• Provident Clinical Research
• Daiichi Sankyo, Inc.

Investigators

• Principal Investigator: Harold E Bays, MD, L-MARC Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01122108
• Other Study ID Numbers: 002
• First Posted: May 13, 2010
• Last Update Posted: Oct 7, 2010
• Last Verified: Sep 1, 2010

• Keywords provided by , ,: Bile Acid Sequestrant; Resin; Lipids; Glucose; Cholesterol; Diabetes Mellitus; Bile Acid Sequestrant Acceptability Scale
• Additional relevant MeSH terms: Colesevelam Hydrochloride; Cholestyramine Resin

Study Results

Participant Flow

Recruitment Details	Recruitment started in April 2010 and ended in May 2010. Enrollment officially closed on May 24th, 2010. All patient screening and study visits were conducted at L-MARC Research Center's clinic.
Pre-assignment Detail	Enrolled subjects were required to meet all of the inclusion and none of the exlusion criteria prior to being randomized to a group assignment. Subjects were also required to undergo vital sign obtainment, a brief physical exam, and a medical history review to ensure they were generally healthy.

Arm/Group Title	Colesevelam HCl 3.75g First, Then Cholestyramine 12g	Cholestyramine 12g First, Then Colesevelam HCl 3.75
Arm/Group Description	Colesevelam HCl 3.75g once orally in the first intervention and Cholestyramine 12g once orally in the second intervention. Both interventions were given on the same day, 30 minutes apart.	Cholestyramine 12g once orally in the first intervention and Colesevelam 3.75g once orally in the second intervention. Both interventions were given on the same day, 30 minutes apart.
Period Title: Overall Study
STARTED	21	21
COMPLETED	21	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Colesevelam HCl (3.75g) vs Cholestyramine (12g)
Arm/Group Description	Although 2 different arms are used in this study, there is only one study group. All subjects received both treatment arms on the same day, just in varying orders. Thus, the participant flow and baseline characteristics are the same for both arms.
Overall Participants	42
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	39 92.9%
>=65 years	3 7.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.98 (1.61)
Sex: Female, Male (Count of Participants)
Female	30 71.4%
Male	12 28.6%
Region of Enrollment (participants) [Number]
United States	42 100%

Outcome Measures

1. Primary Outcome

Title	Patient Acceptability of Colesevelam HCl Powder for Oral Suspension vs. Generic Cholestyramine Via the Bile Acid Sequestrant Acceptability (BASA) Scale, Based Upon an Anticipated Equivalent Cholesterol Lowering Doses of Each Comparator Drug.
Description	The bile acid sequestrant acceptability (BASA) scale has 4 scoring categories: taste, texture, appearance, and mixability. Participants rank each category separately. The best possible score for each category is 5, and the worst possible score for each category is 1.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colesevelam HCl (3.75g)	Cholestyramine (12g)
Arm/Group Description	Although 2 different arms are used in this study, there is only one study group. All subjects received both treatment arms on the same day, just in varying orders. Thus, the participant flow and baseline characteristics are the same for both arms.	Although 2 different arms are used in this study, there is only one study group. All subjects received both treatment arms on the same day, just in varying orders. Thus, the participant flow and baseline characteristics are the same for both arms.
Measure Participants	42	42
Taste Score	3.26 (.17)	2.67 (0.18)
Texture Score	2.62 (0.19)	2.36 (0.19)
Appearance Score	2.69 (0.12)	3.48 (0.15)
Mixability Score	2.74 (0.14)	2.6 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Colesevelam HCl (3.75g), Cholestyramine (12g)
	Comments	The BASA scale was previously developed to effectively compare differing Bile acid sequestrant forumulations. The BASA scale should differentiate subject acceptability of Colesevelam HCl 3.75 vs Cholestyramine 12g based upon the sum of ratings for taste, texture, appearance and mixability. If normality hypothesis was rejected, then further inspection of the distribution utilizing normal quantile-quantile and kernel density plots was employed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	If a sequence was not found to be statistically significant, then that term was removed from final model. Normality of residuals was investigated for each outcome variable using the Shapiro-Wilk test.
	Method	repeated measures analysis of variance
	Comments	Sensitivity analyses were run to evaluate possible product by sequence interactions

2. Other Pre-specified Outcome

Title	Weighted vs. Unweighted Composite BASA Scale Scores
Description	Aggregate scores were calculated for both the unweighted and weighted BASA scale scores for both Colesevlam HCL (3.75G) and Cholestyramine (12g). The best possible total BASA score is 20 and the worst possible total BASA score is 4. For the weighted version of the scale, the best possible total score is 60 and the worst possible total score is 4.
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colesevelam HCl (3.75g)	Cholestyramine (12g)
Arm/Group Description	Although 2 different arms are used in this study, there is only one study group. All subjects received both treatment arms on the same day, just in varying orders. Thus, the participant flow and baseline characteristics are the same for both arms.
Measure Participants	42	42
Total BASA Score	11.31 (0.40)	11.10 (0.43)
Total Weighted BASA Score	27.29 (1.21)	26.05 (1.34)

Adverse Events

Time Frame	Adverse events were collected from the time the subject signed the informed consent to up to 7 days after the study visit.
Adverse Event Reporting Description	Adverse events were assessed in clinic during the study visit and through a follow-up phone call 1-7 days after the study visit.
Arm/Group Title	Cholestyramine (12g)		Colesevelam HCl (3.75 Grams)		More Than 30 Minutes After Last Beverage
Arm/Group Description	Although 2 different arms are used in this study, there is only one study group. All subjects received both treatment arms on the same day, just in varying orders. Thus, the participant flow and baseline characteristics are the same for both arms.		This group summarizes the adverse events that occurred more than 30 mintures after the last beverage administered, and thus cannot be attributed to one specific bile acid sequestrant.
All Cause Mortality
	Cholestyramine (12g)		Colesevelam HCl (3.75 Grams)		More Than 30 Minutes After Last Beverage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cholestyramine (12g)		Colesevelam HCl (3.75 Grams)		More Than 30 Minutes After Last Beverage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Cholestyramine (12g)		Colesevelam HCl (3.75 Grams)		More Than 30 Minutes After Last Beverage
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/42 (4.8%)		3/42 (7.1%)		14/42 (33.3%)
Gastrointestinal disorders
Belching	0/42 (0%)	0	2/42 (4.8%)	2	1/42 (2.4%)	1
Burping	1/42 (2.4%)	1	0/42 (0%)	0	0/42 (0%)	0
Mild Indigestion	1/42 (2.4%)	1	0/42 (0%)	0	2/42 (4.8%)	2
Mild Nausea	0/42 (0%)	0	1/42 (2.4%)	1	0/42 (0%)	0
Abdominal Cramps	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Diarrhea	0/42 (0%)	0	0/42 (0%)	0	2/42 (4.8%)	2
Gas	0/42 (0%)	0	0/42 (0%)	0	2/42 (4.8%)	2
Moderate Indigestion	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Severe Indigestion	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Moderate Nausea	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Vomitting	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Bloating	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
General disorders
Dry Throat	1/42 (2.4%)	1	0/42 (0%)	0	0/32 (0%)	0
Headache	1/42 (2.4%)	1	0/42 (0%)	0	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Intermittent R Back Thigh Pain	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Renal and urinary disorders
Increased Urination	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1

Limitations/Caveats

Used generally healthy subjects, for who lipid-altering medication may not be indicated; Compared the BAS on the same day; Evaluated estimated equal cholesterol lowering doses of each BAS, rather than same g amt of active drug

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.