Colesevelam as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Colesevelam; Placebo; Pioglitazone
Intervention description: Colesevelam 625 mg tablets; Placebo tablets appearing to be colesevelam; 30 mg or 45 mg pioglitazone therapy
Intervention MeSH terms: Pioglitazone; Colesevelam Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 562.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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