Clinical trial NCT00494663 (phase 2, status: terminated)
Conditions: type 2 diabetes
ICD codes: E11.65, E11.9, E11.21, E11.36, E11.41, E11.42, E11.44
Drugs: dio-902, dio-902, dio-902, dio-902 placebo, dio-902, dio-902, dio-902, dio-902 placebo
SMILES: CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1, CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1
Reason stopped: 
    program terminated
  
Eligibility criteria:

        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 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

        Exclusion Criteria:

          -  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