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

NCT ID: NCT00353587

Last Updated: 2015-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 396 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2007-11-30

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.

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MBX-102 200 mg

MBX-102 200 mg once daily for 16 weeks

Group Type: EXPERIMENTAL

MBX-102

Intervention Type: DRUG

MBX-102 200 mg once daily for 16 weeks

MBX-102 400 mg

MBX-102 400 mg once daily for 16 weeks

Group Type: EXPERIMENTAL

MBX-102

Intervention Type: DRUG

MBX-102 400 mg once daily for 16 weeks

MBX-102 600 mg

MBX-102 600 mg once daily for 16 weeks

Group Type: EXPERIMENTAL

MBX-102

Intervention Type: DRUG

MBX-102 600 mg once daily for 16 weeks

Sugar Pill

Placebo comparator once daily for 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

MBX-102 Placebo once daily for 16 weeks

Actos

Actos 30 mg once daily for 16 weeks

Group Type: ACTIVE_COMPARATOR

Actos

Intervention Type: DRUG

Actos 30 mg once daily for 16 weeks

Interventions

MBX-102

MBX-102 200 mg once daily for 16 weeks

Intervention Type: DRUG

MBX-102

MBX-102 400 mg once daily for 16 weeks

Intervention Type: DRUG

MBX-102

MBX-102 600 mg once daily for 16 weeks

Intervention Type: DRUG

Placebo

MBX-102 Placebo once daily for 16 weeks

Intervention Type: DRUG

Actos

Actos 30 mg once daily for 16 weeks

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NEA Clinic

Jonesboro, Arkansas, United States

Associated Pharmaceutical Research Center, Inc.

Buena Park, California, United States

The Intermed Group

Los Angeles, California, United States

LAC/USC Medical Center

Los Angeles, California, United States

International Research Associates, LLC

Miami, Florida, United States

Suncoast Clinical Research, Inc.

Palm Harbor, Florida, United States

Andres Patron DO PA

Pembroke Pines, Florida, United States

Cedar-Crosse Research Center

Chicago, Illinois, United States

Clinical Investigation Specialists, Inc.

Gurnee, Illinois, United States

Olive Branch Research

Olive Branch, Mississippi, United States

Optimed Research, LLC

Columbus, Ohio, United States

Radiant Research - Greer

Greer, South Carolina, United States

Dallas Diabetes & Endocrine Center

Dallas, Texas, United States

Mercury Pharma Services

Houston, Texas, United States

Diabetes Center of the Southwest

Midland, Texas, United States

Diabetes & Glandular Disease Research Associates, P.A.

San Antonio, Texas, United States

McGuire VA Medical Center

Richmond, Virginia, United States

National Clinical Research

Richmond, Virginia, United States

Consultorio Integral de Atencion al Diabetico (CIAD)

Buenos Aires, , Argentina

CIMEL

Buenos Aires, , Argentina

Centro de Atencion Integral en Diabetes, Endocrinologica y Metabolismo

Buenos Aires, , Argentina

Fundacion CIDEA

Buenos Aires, , Argentina

Sanatorio Municipal Dr. Julio Mendez

Buenos Aires, , Argentina

Instituto Medico Especializado

Buenos Aires, , Argentina

Hospital Thompson

Buenos Aires, , Argentina

Clinica Dleta Zarate

Buenos Aires, , Argentina

Hospital Privado de Comunidad

Buenos Aires, , Argentina

Consultorios Asociados de Endocrinologia

Capital Federal, , Argentina

Instituto Latinoamericano de Investigaciones Clinicas

Córdoba, , Argentina

Sanatorio Parque

Córdoba, , Argentina

Fundacion Marcelino Rusculleda Batlle

Córdoba, , Argentina

Instituto de Clinica Medica y Diabetes

Mendoza, , Argentina

Policlio Modelo de Cipoletti

Rio Negro, , Argentina

Hospital San Bernardo

Salta, , Argentina

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica

San Juan Capital, , Argentina

Nizam's Institute of Medical Sciences

Panjagutta, Hyderabad, Andhra Pradesh, India

Bharti Research Institute of Diabetes & Endocrinology

Karnāl, Haryana, India

Amrita Institute of Medical Sciences

Kochi, Kerala, India

Kasturba Medical College Hospital

Attavar, Mangalore, India

Sterling Hospital

Ahmedabad, , India

St. John's Medical College Hospital

Bangalore, , India

M.S. Ramaih Medical College & Hospital

Bangalore, , India

Diacon Hospital

Bangalore, , India

Sri Ramachandra Medical Centre

Chennai, , India

Dr. V. Seshiah Diabetes Care & Research Institute

Chennai, , India

Apollo Gleneages/Dept. of Endocrinology

Kolkata, , India

Diabetes Care and Research Center

Maharashtra, , India

Kasturba Hospital

Manipal, , India

Chowpatty Medical Center

Mumbai, , India

Mediheights Healthcare Pvt. Ltd.

Mumbai, , India

KEM Hospital

Pune, , India

Kerala Institute of Medical Sciences

Trivandrum, , India

Christian Medical College Hospital

Vellore, , India

Endocrinology Institute, Haemek Medical Center

Afula, , Israel

Barzilai Medical Center

Ashkelon, , Israel

Soroka Medical Center

Beersheba, , Israel

Rambam Medical Center

Haifa, , Israel

Linn Medical Center

Haifa, , Israel

Wolfson Medical Center

Holon, , Israel

Hadassah University Hospital

Jerusalem, , Israel

Clalit Health Services

Jerusalem, , Israel

Institution of Diabetes and Metabolism

Nahariya, , Israel

Endocrinology & Diabetes Institute

Petah Tikva, , Israel

Department of Endocrinology, Ziv Medical Center

Safed, , Israel

Zamenhoff Medical Center

Tel Aviv, , Israel

Institute of Metabolic Diseases

Tel Aviv, , Israel

Assaf Haroffe Medical Center

Zrifin, , Israel

Countries

United States; Argentina; India; Israel

Other Identifiers

M102-20509

Identifier Type: -

Identifier Source: org_study_id