E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of dutogliptin over 26 weeks, as evidenced by placebo-corrected changes in HbA1c
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E.2.2 | Secondary objectives of the trial |
To demonstrate safety and tolerability of dutogliptin and the changes in fasting plasma glucose over 26 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Type 2 diabetes mellitus, diagnosed at least 4 months prior to Screening (Visit 1). 2. Male and female subjects with a BMI of 20 to 48 kg/m2, inclusive. Current treatment of Type 2 diabetes mellitus with a stable dose of metformin of ≥2000 mg (or the highest tolerated dose; reason for intolerance must be documented) used in accordance with product labeling for at least 6 weeks prior to Screening (Visit 1). 3. Fasting plasma C-peptide greater than 0.26 nmol/L (> 0.8ng/mL; > 281 pmol/L) at Screening (Visit 1). 4. HbA1c 7.0% – 10.0%, inclusive, at Screening (Visit 1) and Visit 4 (lab results from Visit 3). 5. Stable weight, with no more than a 5 kg weight gain or loss in the 3 months prior to Screening (Visit 1) (by history). 6. Age 18 to 85 years, inclusive. 7. Subjects receiving medication(s) other than anti-diabetic medication that might affect the maintenance or measurement of plasma glucose must be on a stable dose for 4 weeks prior to Screening (Visit 1). All herbal medication taken for the treatment of diabetes must be discontinued for the duration of the study. 8. TSH results must be within normal limits. If taking thyroid hormone, the dose must have been stable for at least 6 weeks prior to Screening (Visit 1). 9. If taking medication(s) for hypertension (including diuretics), the dose(s) must have been stable for at least 4 weeks prior to Screening (Visit 1). 10. Male and non-pregnant, non-lactating (and not planning to become pregnant during the course of the study) female subjects. For men and women of childbearing potential, willingness to use adequate contraception and not become pregnant (or have their partner[s] become pregnant) during the full course of the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to Screening\Visit 1); IUD; Depo Provera; Norplant System implants; bilateral tubal ligation; vasectomy; condom or diaphragm plus either contraceptive sponge, foam, or jelly; and abstinence. 11. Willing to return for all clinic visits and complete all study-related procedures, including self-monitoring of blood glucose. 12. Able to understand and provide informed consent.
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E.4 | Principal exclusion criteria |
1. Currently on anti-diabetic drugs other than metformin. 2. Type 1 diabetes mellitus, mature onset diabetes of the young (MODY), insulin requiring Type 2 diabetes mellitus, or other unusual or rare forms of diabetes mellitus. 3. Elevated blood glucose due to medical treatment or due to a concurrent medical condition other than Type 2 diabetes mellitus. 4. Skin lesions, edema states, diabetic foot, or epilepsy. 5. History of diabetic coma or hypoglycemic episode requiring help in the form of glucose, glucagon, orange juice, etc, from a second person during the 6 months prior to Screening (Visit 1). 6. History of stroke, myocardial infarction, symptomatic coronary artery disease, angina, or arrhythmia within 4 weeks prior to Screening (Visit 1) or any history of congestive heart failure Class III or IV according to the New York Heart Association functional classification system (NYHA, The Stages of Heart Failure). 7. History of or risk for acute pancreatitis or exacerbation of pancreatitis. 8. Inadequately controlled hypertension: systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at Visit 1 or Visit 2. The measurement at Visit 1 or 2 may be repeated if the initial read-out is felt to be inaccurate. 9. Gastrointestinal surgery for obesity (including bypass, gastroplasty, and banding procedures) within the last year prior to Screening (Visit 1) or plans to have such surgery or procedures for removal of excess fatty tissue (e.g., liposuction, breast reduction or augmentation) during the course of the study. 10. Current efforts to lose weight either by participation in a commercial behavior modification/diet program (e.g., Jenny Craig, Weight Watchers) or attempting to lose weight outside of such a program with or without drugs. 11. Current administration of antipsychotic medications (except for PRN use of prochlorperazine for nausea), administration within the past 2 weeks of systemic glucocorticoids at a dose greater than 5 mg of prednisone or equivalent daily, or current administration of products intended to stimulate appetite (e.g., Megace). 12. Except for Type 2 diabetes mellitus, any other uncontrolled, serious pulmonary, cardiovascular, hematologic, renal, gastrointestinal, endocrine, neurological, immunosuppressive, psychiatric, or urogenital disorder; or diseases of skin and its appendages, the eyes, ears, nose, or throat. 13. History or presence of malignancy within the past year. Subjects who have been successfully treated (for 3 months or longer) with no recurrence of basal cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled. 14. HIV, Hepatitis B, or Hepatitis C virus positive (by history only). 15. History of alcohol or substance abuse in the past 2 years or eating disorder diagnosed in the past 5 years. 16. Use of any investigational drug or participation in any investigational study within 30 days prior to Screening (Visit 1). 17. Total bilirubin above the upper limit of normal; creatinine ≥ 1.5 mg/dL (≥ 142 µmol/L) (for males) or creatinine ≥ 1.4 mg/dL (≥ 133 µmol/L) (for females); AST (SGOT) or ALT (SGPT) > 2.5 × the upper limit of normal; alkaline phosphatase > 1.5 × the upper limit of normal; or hemoglobin < 11 g/dL (< 110 g/L). 18. Any condition, disease, disorder or clinically significant laboratory abnormality which, in the opinion of the Investigator, would jeopardize the subject’s appropriate participation in this study or obscure the effects of treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
HbA1c, fasting plasma glucose, % to achieve target HbA1c < 7%. PK and PD (DPP4 inhibition). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |