A Phase 1/2a Study of the 2S,4R Enantiomer of Ketoconazole in Subjects With Type 2 Diabetes Mellitus

NCT00302224 | Completed Phase 1

• 1 other identifier: DIO-501
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

The study is designed to test the safety, tolerability of a newly developed form of ketoconazole (DIO-902) for the treatment of elevated blood sugars in type 2 diabetes. This study also will also examine the effect of the drug on total and LDL cholesterol and blood pressure. Elevated cortisol may contribute to the development of Type II diabetes. The investigational drug DIO-902 may reduce the level of cortisol in blood and therefore provide better control of blood sugar levels in patients with Type II diabetes.

Conditions

Type 2 Diabetes

Keywords

safety; type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of 14 daily doses; To determine the pharmacokinetic (PK) profile in plasma of DIO-902 after a single dose, and after fourteen daily doses; To evaluate the pharmacodynamic effects of fourteen daily doses

Secondary Outcomes (1)

• To explore the impact of treatment with the enantiomer of ketoconazole on markers of inflammation and coagulation as well as on lipomic profiles, pre- and post-treatment

Interventions

2S, 4R Ketoconazole (DIO-902) DRUG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 to 70
• Females are non-lactating and using adequate contraception, in the opinion of the Principal Investigator and negative serum pregnancy test if of child bearing potential (intact uterus and pre-menopausal)
• Pharmacologic treatment for type 2 DM may include the following and must be stable for \> 3 months Glucophage (Metformin) (\< maximum dose of 2550 mg) or Glucophage XR (\< maximum dose of 2000 mg)
• HbA1C level of 6.5 to 10.9%
• Fasting C-peptide level of greater than or equal to 0.8 nmol/L (2.4 ng/mL)
• ACTH stimulation test results with any cortisol level (baseline, 30 or 60 minutes) of \>18 µg/dL
• Normal thyroid stimulating hormone
• lead electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality
• BMI of 26 to 40 kg/m2
• Ability to comprehend and a willingness to provide informed consent

You may not qualify if:

• History of any atherosclerotic disorder (myocardial infarction, angina, cerebrovascular accident, peripheral vascular disease or congestive heart failure secondary to ischemic myocardial injury) that would, in the estimation of the Investigator, make it unsafe to stop all lipid lowering drugs during the course of the study
• Known hypersensitivity or idiosyncratic reaction related to ketoconazole or other imidazole compounds
• History of malignancy (except basal cell carcinoma) within the 3 years before the initial dose of the study medication
• Excessive alcohol intake or drug abuse using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV), criteria
• Any other clinically significant medical condition, as determined by the Investigator. These clinically significant medical conditions include proliferative diabetic retinopathy and neuropathic symptoms that limit activities of daily living
• Participation in another clinical trial and/or treatment received with any investigational agent within one month before the initial dose of study medication
• Concomitant therapy with the following: any antacid or ulcer medication, weight loss medications, oral or injected hypoglycemics (metformin is allowed) or insulin, steroids, cyclosporine, tacrolimus, midazolam, digoxin, coumarin derivatives, phenytoin, rifampin, loratadine, HIV protease inhibitors, spironolactone, thiazide diuretics, calcium channel blockers and erythromycin. Subjects taking lipid lowering medications may be enrolled if Investigator determines that subject does not have any conditions that preclude this cessation and subject is willing to stop such medications 21 days prior to Study Visit 1 through Study Visit 3 (Day 16)
• History of HIV
• Positive hepatitis B (HBsAg) or positive hepatitis C (Hepatitis C antibody) test during Screening
• WBC count \<4000/µL or \>14,000/µL
• Hemoglobin \<12.0 gm/dL in females and \<14.0 gm/dL in males
• Any single hepatic enzyme (ALT, AST, AP and total bilirubin) is greater than the upper limit of the normal reference range used by the central laboratory
• Creatinine \> 1.5 times the upper limit of normal
• Known hypersensitivity to cosyntropin (ACTH) or any component of the formulation (mannitol or sodium chloride)

Sponsors & Collaborators

• DiObex: lead

Study Sites (5)

Asha Thomas, MD - Medstar

Washington D.C., District of Columbia, 20003, United States

Location

Marc Rendell, MD - Creighton University

Omaha, Nebraska, 68131, United States

Location

Dr. Andrew Ahmann, MD - Radiant Research

Portland, Oregon, 97239, United States

Location

Carlos Arauz-Pacheco, MD - Radiant Research

Dallas, Texas, 75247, United States

Location

Sherwin Schwartz, MD - Diabetes and Glandular Disease Clinic

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Sherwin Schwartz, MD

  Diabetes and Glandular Disease Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 10, 2006
• First Posted: March 14, 2006
• Study Start: February 1, 2005
• Study Completion: August 1, 2006
• Last Updated: February 22, 2008

Record last verified: 2008-02

Locations

US (5)