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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00494663




Registration number
NCT00494663
Ethics application status
Date submitted
28/06/2007
Date registered
2/07/2007
Date last updated
13/11/2008

Titles & IDs
Public title
A Phase 2b Study of DIO-902 or DIO-902 Placebo in Addition to Metformin and Atorvastatin or Atorvastatin Placebo for Type 2 Diabetes
Scientific 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)
Secondary ID [1] 0 0
DIO-502
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DIO-902
Treatment: Drugs - DIO-902
Treatment: Drugs - DIO-902
Treatment: Drugs - DIO-902 placebo
Treatment: Drugs - DIO-902
Treatment: Drugs - DIO-902
Treatment: Drugs - DIO-902
Treatment: Drugs - DIO-902 placebo

Experimental: 1 - 150mg DIO-902 + 10mg atorvastatin

Experimental: 2 - 300mg DIO-902 + 10mg atorvastatin

Experimental: 3 - 450mg DIO-902 + 10mg atorvastatin

Placebo Comparator: 4 - DIO-902 Placebo + 10mg atorvastatin

Experimental: 5 - 150mg DIO-902 + atorvastatin placebo

Experimental: 6 - 300mg DIO-902 + atorvastatin placebo

Experimental: 7 - 450mg DIO-902 + atorvastatin placebo

Placebo Comparator: 8 - DIO-902 placebo + atorvastatin placebo


Treatment: Drugs: DIO-902
150mg tablet once per day for 16 weeks

Treatment: Drugs: DIO-902
300mg tablet once per day for 16 weeks

Treatment: Drugs: DIO-902
450mg DIO-902 tablet once daily for 16 weeks

Treatment: Drugs: DIO-902 placebo
DIO-902 placebo tablet once daily for 16 weeks

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

Treatment: Drugs: DIO-902
300mg DIO-902 tablet daily for 16 weeks

Treatment: Drugs: DIO-902
450mg DIO-902 tablet for 16 weeks

Treatment: Drugs: DIO-902 placebo
DIO-902 placebo tablet once daily for 16 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
1. The primary efficacy endpoint will be change from baseline to the end of treatment (Study Visit 6, Week 16) in HbA1c
Timepoint [1] 0 0
16 weeks
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
16 weeks

Eligibility
Key inclusion criteria
-

A subject may be included in this study if he/she meets all of the following criteria:

1. Male or female, age 18 to 75

2. 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:

1. abstinence

2. surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral
oophorectomy) 6 months minimum

3. IUD in place for at least 3 months

4. barrier methods (condom or diaphragm) with spermicide

5. surgical sterilization of the partner (vasectomy for 6 months)

6. hormonal contraceptives for at least 3 months prior to the first dose

3. Diagnosis of type 2 diabetes mellitus (DM) for at least 6 months.

4. 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.

5. HbA1C level of 7.0 to 10.0%

6. Fasting C-peptide level of >0.33 nmol/l (1.0 ng/ml)

7. ACTH stimulation test results with any cortisol level of >18 µg/dl at baseline or 60
minutes

8. Normal complete blood count (CBC) with platelets and differential

9. 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.

10. BMI of 27 to 42 kg/m2 (see Appendix B)

11. Subjects with a history of hypertension may be on a stable anti-hypertensive regimen
for (except those drugs stated under
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criterion 8) for >6 weeks prior to the
Pre-Treatment Visit (Week -4))

12. Ability to comprehend and a willingness to provide informed consent



- A subject may be excluded from this study if he/she meets any of the following
criteria:

1. Previous participation in a clinical trial with DIO-902.

2. 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.

3. Known hypersensitivity or idiosyncratic reaction related to ketoconazole or other
imidazole compounds.

4. History of malignancy (except basal cell carcinoma) within the 3 years before the
initial dose of the study medication.

5. 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)

6. 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.

7. Participation in another clinical trial and/or treatment received with any
investigational agent within one month before the initial dose of study
medication.

8. Concomitant therapy with the following: (See Appendix G for List of Drug Trade
Names)

1. weight loss medications

2. oral or injected hypoglycemics (metformin is allowed) or insulin

3. oral, parenteral or inhaled steroids; nasal, topical ocular, intravitreal,
and low to moderate potency topical steroids are allowed

4. dihydropyridine calcium channel blockers (amlodipine, diltiazem and
verapamil are allowed)

5. H2 antagonists and proton pump inhibitors (liquid and tablet antacids are
allowed)

6. midazolam, triazolam, alprazolam, terfenadine, astemizole, digoxin, coumarin
derivatives, phenytoin, rifampin, HIV protease inhibitors, spironolactone,
aliskiren, erythromycin or clarithromycin, cyclosporine or tacrolimus

7. 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.

9. History of HIV

10. Positive hepatitis B (HbsAg) or positive hepatitis C (Hepatitis C antibody) test
during Screening

11. 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.)

12. CK must not be >2.5X ULN if not clearly related to recent exercise, injury or
unusual activity

13. Creatinine must not be >1.4 mg/dl in females and >1.5 mg/dl in males.

14. Thyroid stimulating hormone level >1.5X ULN

15. History of lactic acidosis

16. Known hypersensitivity to cosyntropin (ACTH) or any component of the formulation
(mannitol or sodium chloride)

17. Known intolerance to statin drugs

18. Any other condition which increases the risk of participation in the trial in the
opinion of the investigator

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [2] 0 0
Lyell McEwin Hospital - North Western Adelaide
Recruitment hospital [3] 0 0
ECRU - Box Hill, Melbourne
Recruitment hospital [4] 0 0
School of Medicine and Pharmacology - Fremantle
Recruitment hospital [5] 0 0
Keough Institute - Nedands
Recruitment hospital [6] 0 0
Endocrinology Research Unit - Herston Road
Recruitment hospital [7] 0 0
Endocrinology Department - St Leonards
Recruitment hospital [8] 0 0
Royal Melbourn Hospital - Victoria
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- North Western Adelaide
Recruitment postcode(s) [3] 0 0
- Box Hill, Melbourne
Recruitment postcode(s) [4] 0 0
6160 - Fremantle
Recruitment postcode(s) [5] 0 0
6009 - Nedands
Recruitment postcode(s) [6] 0 0
QLD 4029 - Herston Road
Recruitment postcode(s) [7] 0 0
NSW 2065 - St Leonards
Recruitment postcode(s) [8] 0 0
- Victoria
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
Oklahoma
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
New Zealand
State/province [11] 0 0
Christchurch
Country [12] 0 0
New Zealand
State/province [12] 0 0
Hamilton
Country [13] 0 0
New Zealand
State/province [13] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
DiObex
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/show/NCT00494663
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sherwyn Schwartz, MD
Address 0 0
Diabetes & Glandular Disease Research Associates
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00494663