Type 2 DiabetesPhase 1/2NCT00302224
A Phase 1/2a Study of the 2S,4R Enantiomer of Ketoconazole in Subjects With Type 2 Diabetes Mellitus
A Phase 1/2 study testing 2S, 4R Ketoconazole (DIO-902) in people with Type 2 Diabetes, run by DiObex at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- 2S, 4R Ketoconazole (DIO-902)
- How many people
- 50 participants
- Where
- 5 sitesUnited States
- Study dates
- Feb 2005to Aug 2006
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Diagnosis of type 2 diabetes mellitus (DM) for at least 6 months. Type 2 diabetes may be untreated or may be treated with diet and exercise only and/or pharmacologic therapy as in Inclusion Criterion 4
- 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)
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- ACTH stimulation test results with any cortisol level (baseline, 30 or 60 minutes) of >18 µg/dL
- Normal thyroid stimulating hormone
- 9.12-lead electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality
- 10.BMI of 26 to 40 kg/m2
- 11.Subjects with a history of hypertension may be on a stable anti-hypertensive regimen (except those drugs stated under Exclusion Criterion 7) for > 2 months
- 12.Ability to comprehend and a willingness to provide informed consent
Who cannot join
- 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
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- 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)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Carlos Arauz-Pacheco, MD - Radiant Research
Dallas, Texas, 75247
Marc Rendell, MD - Creighton University
Omaha, Nebraska, 68131
Dr. Andrew Ahmann, MD - Radiant Research
Portland, Oregon, 97239
Sherwin Schwartz, MD - Diabetes and Glandular Disease Clinic
San Antonio, Texas, 78229
Asha Thomas, MD - Medstar
Washington D.C., District of Columbia, 20003
About this study
Official title: A Phase 1/2a, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Study of Safety, Tolerability, Pharmacokinetics and Activity of 14 Days of Oral Dosing With the 2S,4R Enantiomer of Ketoconazole (DIO-902) in Subjects With Type 2 Diabetes Mellitus
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.
Read the detailed description
DiObex is developing a modified form of ketoconazole (enantiomer) (DIO-902) as an investigational new drug for the treatment of the elevated blood sugar associated with type 2 diabetes. Other benefits may include reduced total and LDL cholesterol, and reduced blood pressure. With chronic treatment, reduced visceral fat may also be seen. Ketoconazole (racemic) is an approved drug for the treatment of a variety of fungal infections. The approved racemic ketoconazole inhibits cortisol synthesis. In patients with Cushings Disease racemic ketoconazole reduces glucose, cholesterol and blood pressure. Elevated cortisol may be a contributing causal factor in the development of type 2 diabetes; clinical trials with racemic ketoconazole have been carried out in these patients. The results of these clinical trials support the concept of treating type 2 diabetes through a lowering of plasma cortisol and provide evidence of the safety and tolerability of racemic ketoconazole. Racemic ketoconazole has, however, been associated with liver toxicity which is generally mild in nature. However, in rare cases (1:10,000 to 15,000 patients) severe liver toxicity may occur, and in extremely rare cases this adverse event may be irreversible and life-threatening. Preclinical results suggest that DIO-902 may be both safer and more efficacious than the racemic mixture.
- Conditions
- Type 2 Diabetes
- Being tested
- 2S, 4R Ketoconazole (DIO-902)
- Keywords
- safety, type 2 diabetes
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2S, 4R Ketoconazole (DIO-902)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2006 (estimated)
- Study startFeb 2005
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- DiObex
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Sherwin Schwartz, MD, Principal investigator, Diabetes and Glandular Disease Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00302224
- Sponsor's protocol ID
- DIO-501
- Status last verified
- Feb 2008
- First submitted
- 10 Mar 2006
- Last updated
- 22 Feb 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Study of Safety, Tolerability, Pharmacokinetics and Activity of 14 Days of Oral Dosing With the 2S,4R Enantiomer of Ketoconazole (DIO-902) in Subjects With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00302224
- Acronym / sponsor ID
- DIO-501
- Conditions
- Type 2 Diabetes
- Keywords
- safety, type 2 diabetes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- DiObexIndustry (pharma, biotech, devices)
- Study start
- Feb 2005
- Study completion
- Aug 2006
- First posted
- 14 Mar 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
DiObex is developing a modified form of ketoconazole (enantiomer) (DIO-902) as an investigational new drug for the treatment of the elevated blood sugar associated with type 2 diabetes. Other benefits may include reduced total and LDL cholesterol, and reduced blood pressure. With chronic treatment, reduced visceral fat may also be seen. Ketoconazole (racemic) is an approved drug for the treatment of a variety of fungal infections. The approved racemic ketoconazole inhibits cortisol synthesis. In patients with Cushings Disease racemic ketoconazole reduces glucose, cholesterol and blood pressure. Elevated cortisol may be a contributing causal factor in the development of type 2 diabetes; clinical trials with racemic ketoconazole have been carried out in these patients. The results of these clinical trials support the concept of treating type 2 diabetes through a lowering of plasma cortisol and provide evidence of the safety and tolerability of racemic ketoconazole. Racemic ketoconazole has, however, been associated with liver toxicity which is generally mild in nature. However, in rare cases (1:10,000 to 15,000 patients) severe liver toxicity may occur, and in extremely rare cases this adverse event may be irreversible and life-threatening. Preclinical results suggest that DIO-902 may be both safer and more efficacious than the racemic mixture.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
- Diagnosis of type 2 diabetes mellitus (DM) for at least 6 months. Type 2 diabetes may be untreated or may be treated with diet and exercise only and/or pharmacologic therapy as in Inclusion Criterion 4
- 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%
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2S, 4R Ketoconazole (DIO-902) | Drug | – |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sherwin Schwartz, MD principal investigator
Diabetes and Glandular Disease Clinic
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 2S, 4R Ketoconazole (DIO-902) in people with Type 2 Diabetes, run by DiObex at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2008.