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Safety and Efficacy Study of Metaglidasen in Type 2 Diabetes in Patients Suboptimally Controlled on Insulin

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ClinicalTrials.gov Identifier: NCT00353587
Recruitment Status : Completed
First Posted : July 18, 2006
Last Update Posted : May 1, 2015
Sponsor:
Information provided by (Responsible Party):
CymaBay Therapeutics, Inc.

Brief Summary:
This is a multicenter, randomized, double-blind, placebo- and active comparator-controlled phase 2/3 study of three dose levels of MBX-102 (200, 400, 600 mg) given orally to patients with type 2 diabetes receiving concomitant therapy with insulin. Eligible patients will be adults with type 2 diabetes who are taking intermediate- and/or long-acting insulin or pre-mixed (e.g., "70/30") insulin, or a combination of insulin and one or two non-TZD hypoglycemic agents including sulfonylurea, metformin, acrabose or Byetta, but who are poorly controlled on their existing therapy. Preference for enrollment will be given to patients on insulin monotherapy. Patients treated with a combination of insulin and other hypoglycemic agent(s) must be willing and able to discontinue and washout of the hypoglycemic agent(s) for the entire duration of the study (in toto, approximately 28 weeks). Patients who are taking fixed doses of a short-acting insulin (e.g., not a "sliding scale") in combination with intermediate-acting insulin may qualify for the study if both the patient and investigator are willing to either change to pre-mixed insulin (e.g., 70/30) or discontinue use of the short acting insulin for at least 26 weeks. Patients treated with a sliding scale of short-acting insulin will not be eligible for enrollment.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: MBX-102 Drug: Placebo Drug: Actos Phase 2 Phase 3

Detailed Description:

This is a multicenter, randomized, double-blind, placebo- and active comparator-controlled phase 2/3 study of three dose levels of MBX-102 (200, 400, 600 mg) given orally to patients with type 2 diabetes receiving concomitant therapy with insulin. Eligible patients will be adults with type 2 diabetes who are taking intermediate- and/or long-acting insulin or pre-mixed (e.g., "70/30") insulin, or a combination of insulin and one or two non-TZD hypoglycemic agents including sulfonylurea, metformin, acrabose or Byetta, but who are poorly controlled on their existing therapy. Preference for enrollment will be given to patients on insulin monotherapy. Patients treated with a combination of insulin and other hypoglycemic agent(s) must be willing and able to discontinue and washout of the hypoglycemic agent(s) for the entire duration of the study (in toto, approximately 28 weeks). Patients who are taking fixed doses of a short-acting insulin (e.g., not a "sliding scale") in combination with intermediate-acting insulin may qualify for the study if both the patient and investigator are willing to either change to pre-mixed insulin (e.g., 70/30) or discontinue use of the short acting insulin for at least 26 weeks. Patients treated with a sliding scale of short-acting insulin will not be eligible for enrollment.

Following any insulin dose adjustment during the first few weeks of the study, insulin dose and regimen should remain constant for the duration of the study.

No stand alone (e.g., other than pre-mixed) short- or ultrashort-acting insulin and/or sliding scale will be allowed for the entire duration of the study.

A minimum of 400 patients will be randomized in this study (approximately 80 to each of the five treatment arms). Additional patients may be enrolled as appropriate to replace screen failures and drop-outs during the initial period of the study.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 396 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2/3, Randomized, Double-blind, Placebo- and Active Comparator-controlled, Parallel, Multicenter Study to Determine Safety and Efficacy of Metaglidasen in Treatment of Type 2 Diabetes Suboptimally Controlled on Insulin
Study Start Date : May 2006
Actual Primary Completion Date : November 2007
Actual Study Completion Date : November 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Arm Intervention/treatment
Experimental: MBX-102 200 mg
MBX-102 200 mg once daily for 16 weeks
Drug: MBX-102
MBX-102 200 mg once daily for 16 weeks

Experimental: MBX-102 400 mg
MBX-102 400 mg once daily for 16 weeks
Drug: MBX-102
MBX-102 400 mg once daily for 16 weeks

Experimental: MBX-102 600 mg
MBX-102 600 mg once daily for 16 weeks
Drug: MBX-102
MBX-102 600 mg once daily for 16 weeks

Placebo Comparator: Sugar Pill
Placebo comparator once daily for 16 weeks
Drug: Placebo
MBX-102 Placebo once daily for 16 weeks

Active Comparator: Actos
Actos 30 mg once daily for 16 weeks
Drug: Actos
Actos 30 mg once daily for 16 weeks




Primary Outcome Measures :
  1. Evaluate effects of MBX-102 administered orally at doses of 200, 400 and 600 mg daily for 16 weeks, on glucose control, as measured by HbA1c
  2. Evaluate safety of MBX-102 with particular emphasis on endpoints of weight gain and edema


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes (as described by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus24) treated with insulin alone (a stable dose of long and/or intermediate-acting insulin or pre-mixed insulin e.g., "70/30") ≥ 30 units/day for at least 3 months, but poorly controlled on their existing therapy
  • Or, patients treated with insulin (as above) in combination with non-TZD hypoglycemic agents (e.g., a sulfonylurea, metformin, acrabose, or Byetta for at least 3 months, but poorly controlled on their existing therapy
  • Or, patients treated with fixed doses of short-acting insulin in combination with intermediate-acting insulin for at least 3 months, but poorly controlled on their existing therapy
  • Patients in last 2 categories must be willing to discontinue the use of OHA and/or short-acting insulin (or change to pre-mixed insulin) for at least 26 weeks.
  • Male or female, 18-75 years of age
  • Provide informed consent and agree to comply with study requirements
  • Current monotherapy insulin dose regimen ≥ 30 units/day (stable for 8-week Run-in/stabilization Period); or patients who need insulin dose adjustment must have a stabilized dose ≥ 30 units/day. Patients must not have taken TZDs within 5 months of screening
  • All female patients must be surgically sterile, post-menopausal (at least 40 years of age with no history of menses for at least 2 years) or agree to use adequate contraception(s) that must include a barrier method (other methods may include oral contraceptives, double barrier methods, intra-uterine devices, or abstinence). Depo contraceptives are excluded
  • Female patients must not be pregnant or lactating
  • BMI 26-44 kg/m2
  • Hemoglobin A1c must be ≥7.5%, ≤11.5% at both Screening and Visit 4
  • Patients must have a FPG ≤ 220 mg/dl
  • Patients must have liver function tests ≤ 2X the upper limits of normal for AST, ALT, and bilirubin, and ≤ 2.5X the upper limits of normal for ALP and GGT
  • Patients must have serum creatinine ≤ 1.8 mg/dl for males and ≤ 1.5 mg/dl for females and BUN ≤ 40 mg/dl
  • Fecal occult blood test must be negative
  • All other clinical laboratory parameters must be within normal limits or considered not clinically significant for participation in this study, including: hematology, coagulation, other serum chemistry, and other urinalysis parameters
  • TSH must be ≤ 3x ULN and patient clinically euthyroid in opinion of investigator. If TSH is > ULN but ≤ 3x ULN, and patient is clinically euthyroid, FT4 should be drawn and must be WNL
  • Electrocardiogram (ECG) must be normal, or considered not clinically significant, for participation in this study
  • Patients must have a blood pressure ≤ 160/90 mm/hg including hypertensive patients controlled with medication

Exclusion Criteria:

Patients will be excluded from study participation if any of the following applies:

  • History of diabetes secondary to pancreatitis or pancreatectomy
  • Requirement for short-acting insulin during the study
  • Weight loss > 10 pounds in the three months prior to study
  • History of TZD use (Actos or Avandia) within 5 months of Screening Visit
  • History of TZD discontinuation due to side effect or lack of efficacy
  • Prior history of endoscopically or radiographically documented peptic ulcer disease within last 5 years (unless patient had documented H. pylori infection with subsequent treatment and no recurrence)
  • Prior history of GI bleeding within last 5 years (except for hemorrhoids or perianal disease)
  • Known infection with the human immunodeficiency virus (HIV) or history of viral hepatitis type B or C
  • History of congestive heart failure within last 5 years (NYHA Class III-IV)
  • History of significant pulmonary disease, myocardial infarction, cerebrovascular accident, or nephrotic syndrome within last 1 year
  • Elevated creatine phosphokinase (> 2X the upper limits of normal)
  • Malignancy within the last 5 years (except resected basal cell carcinoma)
  • Ongoing active infection, as evidenced by symptoms such as temperature > 38.5° C and/or clinically significant elevation in WBC count (i.e., not asymptomatic colonization)
  • Change in treatment with lipid-lowering agent after screening visit
  • Current or expected requirement for anticoagulant therapy [except for low- dose (≤ 325 mg/d) aspirin]
  • Current or expected treatment with phenytoin
  • Current or anticipated treatment with non-steroidal anti-inflammatory drugs (i.e., naproxen, ibuprofen, Vioxx, Celebrex, indomethacin, etc.). However, patients may take aspirin < 325 mg/day for cardiovascular prophylaxis
  • Known hypersensitivity to NSAIDs
  • Treatment with any other investigational therapy within the 30 days prior to Screening Visit
  • History of illicit drug or alcohol abuse within last 1 year
  • Current or expected treatment with systemic corticosteroids (except topical, ophthalmic, intra-articular, or inhaled at a dose < 1600 μg/day)
  • Any other condition that compromises the ability of the patient to provide informed consent or to comply with the objectives and procedures of this protocol, as judged by the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00353587


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Sponsors and Collaborators
CymaBay Therapeutics, Inc.

Responsible Party: CymaBay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00353587     History of Changes
Other Study ID Numbers: M102-20509
First Posted: July 18, 2006    Key Record Dates
Last Update Posted: May 1, 2015
Last Verified: April 2015

Keywords provided by CymaBay Therapeutics, Inc.:
insulin sensitizer
type 2 diabetes
diabetes
glucose control

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs