Randomized, Double-blind, Active-controlled, Study of Rivoglitazone in Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Rivoglitazone HCl; rivoglitazone HCl; rivoglitazone HCl; placebo; pioglitazone HCl; pioglitazone HCl; pioglitazone HCl 45 mg; placebo; metformin
Intervention description: 0.5 mg tablets administered orally, once daily; 1.0 mg tablets administered orally, once daily; 1.5 mg tablets administered orally, once daily; placebo tablets matching rivoglitazone tablets administered orally, once daily; 15 mg capsules administered orally, once daily; 30 mg capsules administered orally, once daily; 45 mg capsules administered orally, once daily; placebo capsules for pioglitazone administered orally, once daily; Oral tablets. Rescue medication.
Intervention MeSH terms: Metformin; Pioglitazone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a 26-week, multicenter, randomized, double-blind, placebo and active
      comparator-controlled, parallel-group study in participants with type 2 diabetes currently
      sub-optimally controlled by diet and exercise or with non-thiazolidinedione antihyperglycemic
      monotherapy. Pioglitazone is used as active comparator. The total duration of a participant's
      participation will be approximately 30 weeks, including a 2-week placebo lead-in period, a
      26-week double-blind treatment period, and a 2-week post-treatment follow-up period.
      Participants who complete the randomized portion of the study per protocol may have the
      opportunity to continue in a long-term extension study of active treatments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provided written informed consent at screening.

          -  Diagnosed with type 2 diabetes mellitus.

          -  Glycosylated hemoglobin (A1c) >7.0% and ≤8.5% at screening.

          -  Male or female ≥18 years of age.

          -  Women of childbearing potential must have been using an adequate method of
             contraception to avoid pregnancy throughout the study, and for up to 4 weeks after
             study completion.

          -  Fasting C-peptide level >0.5 ng/mL at screening.

          -  Currently being treated with a stable dose of an approved non-thiazolidinedione
             antihyperglycemic medication (including sulfonylureas, meglitinides, insulin
             secretagogues, metformin, or α-glucosidase inhibitors) given as monotherapy, for at
             least 3 months prior to screening, and could discontinue that antihyperglycemic
             medication at Visit 2 (Week -2) and for the duration of the study. OR

          -  Untreated and had not taken any antihyperglycemic agent during the 2 months prior to
             screening; if not treated with an oral antihyperglycemic agent, the participant was
             considered by the investigator to have failed diet and exercise modification as the
             sole treatment for type 2 diabetes mellitus.

          -  Clinically stable in regard to medical conditions other than type 2 diabetes mellitus.

          -  Concomitant medications (other than oral antihyperglycemic agents) were at stable
             doses for at least 30 days prior to enrollment and were not anticipated to need
             adjustment during the study period.

        Exclusion Criteria:

          -  History of type 1 diabetes and/or history of ketoacidosis.

          -  History of long-term (>2 months) therapy with insulin.

          -  History of prior treatment failure with, or intolerance of, a thiazolidinedione (ie,
             rosiglitazone, troglitazone, or pioglitazone).

          -  Treatment with a fibrate lipid-lowering agent (eg, fenofibrate, gemfibrozil).

          -  Confirmed repeat fasting glucose (≥2 readings of fasting blood glucose) >240 mg/dL
             (13.3 mmol/L) during the 2-week washout/stabilization and placebo run-in period
             (Period A).

          -  Body mass index (BMI) >45 kg/m2 at screening.

          -  History of weight loss >10% over the 3 months prior to screening.

          -  Female participant who was pregnant or breastfeeding.

          -  Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure

             ≥110 mmHg.

          -  Any known history of congestive heart failure prior to screening.

          -  History of unstable angina, myocardial infarction, cerebrovascular accident, transient
             ischemic attack, or any revascularization within 6 months prior to screening. History
             of malignancy (except participants who had been disease-free for >10 years), or whose
             malignancy was a basal or squamous cell skin carcinoma. Any history of bladder cancer
             was an exclusion from participation. Women with a history of cervical dysplasia (CIN2
             or higher) were to be excluded unless 2 consecutive normal cervical smears had
             subsequently been recorded prior to enrollment.

          -  Impaired liver function including evidence of acute or chronic hepatitis or liver
             disease by medical history, clinical signs or symptoms, or laboratory results.

          -  Evidence for ongoing infectious liver disease with positive hepatitis A antigen or
             immunoglobulin M antibody, hepatitis B surface antigen, or antibodies to hepatitis C
             virus. Participants with normal liver function tests and isolated positive antibodies
             to hepatitis B virus could have been included.

          -  Known (or evidence of) infection with human immunodeficiency virus.

          -  Known hemoglobinopathy or chronic anemia that required specific treatment within 5
             years of the screening visit.

          -  History of alcohol or drug abuse within 1 year prior to screening.

          -  History of unstable major psychiatric disorders. Known or suspected allergy or
             hypersensitivity to thiazolidinedione agents.

          -  Clinically significant abnormalities in any pre-randomization laboratory analyses
             that, in the investigator's opinion, comprised an undue risk with the participant's
             participation, or could potentially confound results of the study.

        Unexplained hematuria (>3 red blood cells per high-powered field by urine microscopy).

          -  Blood donation of ≥1 pint (0.5 liter) within the past 30 days prior to screening or
             plasma donation within 7 days prior to the screening visit (Visit 1).

          -  Prior known or possible exposure to rivoglitazone.

          -  Contraindication to treatment with pioglitazone once daily.

          -  Known or suspected allergy, hypersensitivity, or intolerance to the excipients of the
             investigational study medication.

          -  Participation in an interventional medical, surgical, or pharmaceutical study within
             30 days prior to the screening visit (Visit 1).

          -  Any condition or concomitant therapy that, in the opinion of the investigator, might
             have posed a risk to the participant or made participation not in the participant's
             best interest.

          -  A direct or familial relationship with the Sponsor, investigator, or site personnel
             affiliated with the study.