Clinical trial NCT00789750: Colesevelam as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus
Official title: A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study of the Efficacy and Safety of WELCHOL as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2008-11-13
Enrollment: 562
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current study investigates colesevelam as add-on therapy to pioglitazone to improve glycemic control in subjects with type 2 diabetes mellitus not adequately controlled with pioglitazone monotherapy or pioglitazone in combination with either metformin or a sulfonylurea. The study will evaluate if colesevelam add-on to pioglitazone therapy for type 2 diabetes mellitus will be safe, well tolerated, and efficacious.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Type 2 diabetes mellitus
* Inadequate glycemic control on a stable dose (at least 2 months prior to screening) of pioglitazone at 30 or 45 mg/day, with or without one or two other oral antidiabetic medications \[metformin or a sulfonylurea, or dipeptidyl peptidase (DPP-IV) inhibitor\]
* Hemoglobin A1c (HbA1c) \>= 7.5% and =\< 9.5% at screening
* Fasting plasma glucose =\<240 mg/dL at randomization (Week 0/Day 1).
* Male or female \>= 18 years of age.
* Women of childbearing potential must be using an adequate method of contraception as detailed per-protocol
* Fasting C-peptide level \>0.5 ng/mL at screening
* Clinically stable in regards to medical conditions other than type 2 diabetes
* Concomitant medications are at stable doses for at least 30 days prior to enrollment, and are not anticipated to need adjustment during the study period

Exclusion Criteria:

* History of Type 1 diabetes and/or history of ketoacidosis
* History of bowel obstruction
* History of hypertriglyceridemia-induced pancreatitis
* Fasting serum triglyceride concentration \>500 mg/dL
* History of dysphagia, swallowing disorders, gastroparesis, other gastrointestinal motility disorders, major gastrointestinal surgery
* History of insulin use \>= 2 weeks duration during the previous 3 months or a total of \>2 months insulin therapy at any time prior to screening
* Treatment with bile acid sequestrants, including colesevelam within 3 months prior to screening
* Female subject who is pregnant or breastfeeding
* History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, or any revascularization within 6 months prior to screening

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in HbA1c at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in HbA1c at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in HbA1c at Week 16
timeFrame: Baseline, Week 16
measure: Number of Participants Achieving an HbA1c Goal of <7.0%
timeFrame: Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline, Week 24
measure: Number of Participants With a Decrease of >= 0.7 Percent in HbA1c
timeFrame: Week 24
measure: Number of Participants With a Decrease of >= 0.5 Percent in HbA1c
timeFrame: Week 24
measure: Number of Participants With a Reduction in FPG of >= 30 mg/dL
timeFrame: Week 24
measure: Percent Change From Baseline in Total Cholesterol (TC)
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Non-HDL-C
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Triglycerides (TG)
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Apolipoprotein A-1 (Apo A-I)
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Apolipoprotein B (Apo B)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Insulin Levels
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting C-peptide
timeFrame: Baseline, Week 24
measure: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Montgomery
country: United States
state: Alabama
city: Montgomery
country: United States
state: Alabama
city: Green Valley
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Searcy
country: United States
state: Arkansas
city: Buena Park
country: United States
state: California
city: Burbank
country: United States
state: California
city: Chino
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: La Mirada
country: United States
state: California
city: Lincoln
country: United States
state: California
city: Lomita
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: Modesto
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Tustin
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Coral Gables
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Delray Beach
country: United States
state: Florida
city: Gulf Breeze
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Ormond Beach
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Sanford
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: Winter Haven
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Columbus
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: East Point
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Stockbridge
country: United States
state: Georgia
city: Tucker
country: United States
state: Georgia
city: Waycross
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state: Georgia
city: Nampa
country: United States
state: Idaho
city: Arlington Heights
country: United States
state: Illinois
city: Chicago
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state: Illinois
city: Bloomington
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state: Indiana
city: Evansville
country: United States
state: Indiana
city: LaPorte
country: United States
state: Indiana
city: South Bend
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state: Indiana
city: Crestview Hills
country: United States
state: Kentucky
city: Paducah
country: United States
state: Kentucky
city: Lafayette
country: United States
state: Louisiana
city: Prince Frederick
country: United States
state: Maryland
city: Silver Spring
country: United States
state: Maryland
city: New Bedford
country: United States
state: Massachusetts
city: Southfield
country: United States
state: Michigan
city: Brooklyn Center
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Port Gibson
country: United States
state: Mississippi
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Belvidere
country: United States
state: New Jersey
city: Berlin
country: United States
state: New Jersey
city: Clifton
country: United States
state: New Jersey
city: Lumberton
country: United States
state: New Jersey
city: Mine Hill
country: United States
state: New Jersey
city: New Windsor
country: United States
state: New York
city: North Massapequa
country: United States
state: New York
city: Tonawanda
country: United States
state: New York
city: West Seneca
country: United States
state: New York
city: Lexington
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Cuyahoga Falls
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Shaker Heights
country: United States
state: Ohio
city: Stow
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Harrisburg
country: United States
state: Pennsylvania
city: Jersey Shore
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Upper Saint Clair
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Germantown
country: United States
state: Tennessee
city: Jackson
country: United States
state: Tennessee
city: Murfreesboro
country: United States
state: Tennessee
city: New Tazewell
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Grand Prairie
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Alexandria
country: United States
state: Virginia
city: Danville
country: United States
state: Virginia
city: Manassas
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Salem
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
city: Lakewood
country: United States
state: Washington
city: Kenosha
country: United States
state: Wisconsin
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: Rosenstock J, Truitt KE, Baz-Hecht M, Ford DM, Tao B, Chou HS. Efficacy and safety of colesevelam in combination with pioglitazone in patients with type 2 diabetes mellitus. Horm Metab Res. 2014 Dec;46(13):943-9. doi: 10.1055/s-0034-1383648. Epub 2014 Jul 23.