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Type 2 DiabetesPhase 2NCT00494663

A Phase 2b Study of DIO-902 or DIO-902 Placebo in Addition to Metformin and Atorvastatin or Atorvastatin Placebo for Type 2 Diabetes

A Phase 2 study testing DIO-902 in people with Type 2 Diabetes, run by DiObex at 24 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

DiObex Inc. is developing an experimental drug (DIO-902) that is made up of part of the ketoconazole molecule for the treatment of elevated blood glucose associated with type 2 diabetes mellitus. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Type 2 Diabetes
What is being tested?
DIO-902
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
200 participants
Where
24 sitesin 3 countries
Study dates
Jul 2007to Dec 2008
Phase
Phase 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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • -
  • A subject may be included in this study if he/she meets all of the following criteria:
  • Male or female, age 18 to 75
  • Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use the following acceptable birth control methods beginning at the Screening Visit and throughout the study:
  • abstinence
  • surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum
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  • IUD in place for at least 3 months
  • barrier methods (condom or diaphragm) with spermicide
  • surgical sterilization of the partner (vasectomy for 6 months)
  • hormonal contraceptives for at least 3 months prior to the first dose
  • Diagnosis of type 2 diabetes mellitus (DM) for at least 6 months.
  • Type 2 diabetes may be treated only with metformin (metformin hydrochloride tablets or metformin hydrochloride extended-release tablets) at a total daily dose of 500 mg to the maximum labeled dose. (See Appendix G for List of Drug Trade Names).The dose of metformin must be stable for >8 weeks prior to the Pre-Treatment Visit (Week -4) and throughout the course of the study. The subject must not be on any other pharmacologic or over-the-counter treatments for diabetes.
  • HbA1C level of 7.0 to 10.0%
  • Fasting C-peptide level of >0.33 nmol/l (1.0 ng/ml)
  • ACTH stimulation test results with any cortisol level of >18 µg/dl at baseline or 60 minutes
  • Normal complete blood count (CBC) with platelets and differential
  • 12-lead electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality. Subjects with QTc interval of >450 msec will be excluded from the study.
  • BMI of 27 to 42 kg/m2 (see Appendix B)
  • Subjects with a history of hypertension may be on a stable anti-hypertensive regimen for (except those drugs stated under Exclusion Criterion 8) for >6 weeks prior to the Pre-Treatment Visit (Week -4))
  • Ability to comprehend and a willingness to provide informed consent

Who cannot join

  • A subject may be excluded from this study if he/she meets any of the following criteria:
  • Previous participation in a clinical trial with DIO-902.
  • History of any atherosclerotic disorder (myocardial infarction, unstable 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 for up to 12 weeks 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 (>20 g per day for females (1.5 standard alcohol drinks) or >30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) or drug abuse. (1.0 fluid oz (US) = 29.57 ml)
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  • Any other clinically significant medical condition, as determined by the Investigator. These clinically significant medical conditions include, but are not limited to, uncontrolled hypertension, NYHA class III or IV CHF, 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: (See Appendix G for List of Drug Trade Names)
  • weight loss medications
  • oral or injected hypoglycemics (metformin is allowed) or insulin
  • oral, parenteral or inhaled steroids; nasal, topical ocular, intravitreal, and low to moderate potency topical steroids are allowed
  • dihydropyridine calcium channel blockers (amlodipine, diltiazem and verapamil are allowed)
  • H2 antagonists and proton pump inhibitors (liquid and tablet antacids are allowed)
  • midazolam, triazolam, alprazolam, terfenadine, astemizole, digoxin, coumarin derivatives, phenytoin, rifampin, HIV protease inhibitors, spironolactone, aliskiren, erythromycin or clarithromycin, cyclosporine or tacrolimus
  • Subjects currently taking lipid lowering medications may be enrolled if the Investigator determines that the subject does not have any conditions that preclude cessation of lipid lowering treatment for up to 12 weeks. [All subjects will be required to discontinue all lipid lowering therapies during the 4 week Pre-Treatment Period and will then be randomized to receive either atorvastatin 10 mg or atorvastatin placebo during the first 8 weeks of the Treatment Period. All subjects will then receive atorvastatin 10 mg during weeks 8 to 16 of the Treatment Period.] Subjects may not be on any other lipid lowering agent through Visit 7 (Week 20) of the study.
  • History of HIV
  • Positive hepatitis B (HbsAg) or positive hepatitis C (Hepatitis C antibody) test during Screening
  • Liver function tests must not be above the following cut-offs: ALT and/or AST >3.0X ULN, AP >1.5X ULN and total bilirubin >ULN. (If all LFTs are WNL and total bilirubin is elevated, a retest of direct and indirect bilirubin may be performed. Subjects with indirect total bilirubin up to 3X ULN (presumed Gilbert's syndrome) may be enrolled if all other LFTs are WNL.)
  • CK must not be >2.5X ULN if not clearly related to recent exercise, injury or unusual activity
  • Creatinine must not be >1.4 mg/dl in females and >1.5 mg/dl in males.
  • Thyroid stimulating hormone level >1.5X ULN
  • History of lactic acidosis
  • Known hypersensitivity to cosyntropin (ACTH) or any component of the formulation (mannitol or sodium chloride)
  • Known intolerance to statin drugs
  • Any other condition which increases the risk of participation in the trial in the opinion of the investigator

Trial locations and contacts

24 sites in 3 countries.

24 sites in 3 countries

United States12 sites

  • Covance CRU

    Austin, Texas, 78752

  • Diabetes Research Goup University of Hawaii at Manoa

    Honolulu, Hawaii, 96813

  • Research Solutions

    Jonesboro, Arkansas, 72401

  • Advanced Medical Research

    Lakewood, California, 90712

  • Arkansas Primary Care Clinic

    Little Rock, Arkansas, 72211

  • Dr. Terence Hart

    Muscle Shoals, Alabama, 35662

  • Creighton Diabetes Center

    Omaha, Nebraska, 68131

  • Covance Clinical Research Unit - Dr. Andrew Ahmann

    Portland, Oregon, 927239

  • Diabetes Glandular and Disease Research Associates

    San Antonio, Texas, 78229

  • Mills-Peninsula Helath Services

    San Mateo, California, 94401

  • Genova Research

    Tucson, Arizona, 85741

  • AHS Oklahoma Physician Group

    Tulsa, Oklahoma, 74104

Other trials in United States

Australia8 sites

  • Flinders Medical Centre

    Adelaide, South Australia

  • ECRU

    Box Hill, Melbourne, Victoria

  • School of Medicine and Pharmacology

    Fremantle, Western Australia, 6160

  • Endocrinology Research Unit

    Herston Road, QLD 4029

  • Keough Institute

    Nedands, Western Australia, 6009

  • Lyell McEwin Hospital

    North Western Adelaide, South Australia

  • Endocrinology Department

    St Leonards, NSW 2065

  • Royal Melbourn Hospital

    Victoria

Other trials in Australia

New Zealand4 sites

  • Lipid and Diabetes Research

    Christchurch

  • Waikaito Hospital

    Hamilton

  • Middlemore Hospital

    Otahuhu, Auckland

  • Diabetes Centre

    Wellington

Other trials in New Zealand

About this study

Official title: A Phase 2b, Randomized, Double-Blind, Parallel-Group, Study of Safety and Efficacy of 16 Weeks of Treatment With DIO-902 or DIO-902 Placebo in Addition to Metformin and Atorvastatin or Atorvastatin Placebo in Subjects With Type 2 Diabetes Mellitus (Protocol No. DIO-502)

DiObex Inc. is developing an experimental drug (DIO-902) that is made up of part of the ketoconazole molecule for the treatment of elevated blood glucose associated with type 2 diabetes mellitus. Ketoconazole (Nizoral®) is a drug available by prescription for the treatment of fungal infections however DIO-902 is an investigational drug. DIO-902 may lower blood glucose by lowering levels of a naturally occurring hormone called cortisol. Elevated cortisol may contribute to the development of type 2 diabetes.

The purpose of this research study is to test the safety of DIO-902 when taken by mouth with metformin and the cholesterol-lowering drug atorvastatin to determine the type and severity of any side effects from this treatment.

Other purposes of the study are to see how the treatment affects your blood glucose levels, cholesterol levels, blood pressure, and waist circumference.

Read the detailed description

DIO-902 may lower blood glucose by lowering levels of a naturally occurring hormone called cortisol. Elevated cortisol may contribute to the development of type 2 diabetes. Clinical trials with ketoconazole have been carried out in patients with type 2 diabetes. Three clinical trials with DIO-902 have been completed in which 37 patients with type 2 diabetes and 42 normal healthy volunteers (people without type 2 diabetes) were enrolled. Patients in these studies received multiple doses of DIO-902. DIO-902 may reduce the level of cortisol in your blood and therefore may provide you with better control of your blood glucose levels.

STUDY DRUG ASSIGNMENT

You will be randomized, that is, given a 1 in 4 chance of receiving either 150mg/day of DIO-902, 300mg/day of DIO-902, 450mg/day of DIO-902 or DIO-902 placebo and a 1 in 2 chance of receiving 10mg/day of atorvastatin or atorvastatin placebo. The study drug is a tablet and will be taken by mouth with water. You will take 3 tablets of DIO-902 or DIO-902 placebo and 1 tablet of atorvastatin or atorvastatin placebo each day. The tablets will be taken at the same time each day (2200h or 10:00pm). Neither you nor your doctor will know which dose of DIO-902 or DIO-902 placebo you are on or whether you are taking the atorvastatin or atorvastatin placebo. If necessary, your doctor has a way of finding out which dose you were assigned.

Atorvastatin

If you are taking any cholesterol-lowering drugs, these drugs must be discontinued on the day prior to the Pre-Treatment Visit (Week -4) and for the duration of the study. At Visit 1 (Week 0) you will be assigned to DIO-902 or DIO-902 placebo and to either atorvastatin or atorvastatin placebo. You will continue to take the assigned drug until Study Visit 4 (Week 8). At Study Visit 4 (Week 8) all patients will begin taking atorvastatin through the remainder of the study. Your DIO-902 or DIO-902 placebo assignment will remain the same. Atorvastatin tablets will be supplied to you until Study Visit 6 (Week 16). At this visit you will be given a prescription for a 28 day supply of atorvastatin 10mg.day to last until Study Visit 7 (Week 20).

There will a total of 9 study visits. At each visit all or some of the following will occur: blood and urine samples will be taken, physical exam, assessment of side effects, and ECG will be performed.

Conditions
Type 2 Diabetes
Being tested
DIO-902, DIO-902 placebo
Keywords
diabetes, type 2 diabetes, cholesterol
Medical subject headings
Diabetes Mellitus, Type 2, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DIO-902Drug

    Also called 2S,4R enantionmer of ketoconazole

    150mg tablet once per day for 16 weeks

  • DIO-902Drug

    Also called 2S,4R enantiomer of ketoconazole

    300mg tablet once per day for 16 weeks

  • DIO-902Drug

    Also called 2S,4R enantiomer of ketoconazole

    450mg DIO-902 tablet once daily for 16 weeks

  • DIO-902 placeboDrug

    DIO-902 placebo tablet once daily for 16 weeks

  • DIO-902Drug

    Also called 2S,4R enantiomer of ketoconazole

    150mg tablet of DIO-902 once daily for 16 weeks

  • DIO-902Drug

    Also called 2S,4R enantiomer of ketoconazole

    300mg DIO-902 tablet daily for 16 weeks

  • DIO-902Drug

    Also called 2S,4R enantiomer of ketoconazole

    450mg DIO-902 tablet for 16 weeks

  • DIO-902 placeboDrug

    DIO-902 placebo tablet once daily for 16 weeks

Study groups in NCT00494663
Study groupRoleWhat they receive
1Experimental150mg DIO-902 + 10mg atorvastatin
Receives: Drug: DIO-902
2Experimental300mg DIO-902 + 10mg atorvastatin
Receives: Drug: DIO-902
3Experimental450mg DIO-902 + 10mg atorvastatin
Receives: Drug: DIO-902
4Placebo comparatorDIO-902 Placebo + 10mg atorvastatin
Receives: Drug: DIO-902 placebo
5Experimental150mg DIO-902 + atorvastatin placebo
Receives: Drug: DIO-902
6Experimental300mg DIO-902 + atorvastatin placebo
Receives: Drug: DIO-902
7Experimental450mg DIO-902 + atorvastatin placebo
Receives: Drug: DIO-902
8Placebo comparatorDIO-902 placebo + atorvastatin placebo
Receives: Drug: DIO-902 placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1. The primary efficacy endpoint will be change from baseline to the end of treatment (Study Visit 6, Week 16) in HbA1c

    Measured: 16 weeks

Secondary outcomes (1)

  1. 1. Change from baseline to Week 8 in total and LDL-cholesterol (LDL-C) 2. Change from baseline to the end of treatment (Week 16) in the following : Seated blood pressure (systolic, diastolic and mean arterial pressure) Fasting blood glucose

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2007 (estimated)
  2. Study startJul 2007
  3. Primary completionMar 2008 (estimated)
  4. Study completionDec 2008 (estimated)

Why it stopped: Program Terminated

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00494663
Sponsor's protocol ID
DIO-502
Status last verified
Nov 2008
First submitted
28 Jun 2007
Last updated
13 Nov 2008
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DIO-902 in people with Type 2 Diabetes, run by DiObex at 24 sites in 3 countries.

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 20 inclusion and 26 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: stopped early, as of the sponsor's last update on 13 Nov 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Australia, New Zealand. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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 was stopped early (reason given: Program Terminated). Results are not available in the source record.

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?

1. The primary efficacy endpoint will be change from baseline to the end of treatment (Study Visit 6, Week 16) in HbA1c (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00494663.

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 13 Nov 2008.

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Clinical Trial NCT00494663 | AzTrials