E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus (T2DM) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 evaluate the safety and efficacy of dutogliptin in patients with type 2 diabetes mellitus (T2DM) who are receiving background therapy with pioglitazone.
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E.2.2 | Secondary objectives of the trial |
There are no secondary objectives in the trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be able to understand and provide written informed consent before participating in any study-related procedures 2. Be male or female outpatients 18 to 75 years of age, inclusive 3. Be willing to return for all clinic visits and complete all study-related procedures, including self-monitoring of blood glucose 4. Have a body mass index of 20 to 48 kg/m2 5. Have stable weight, with no more than a 7% gain or loss in the previous 3 months 6. Be diagnosed with T2DM at least 3 months before the Screening Visit (Visit 1). Verification of the diagnosis should be made by obtaining documentation or written confirmation from the physician treating the patient’s diabetes 7. If taking a medication(s) for hypertension (including a diuretic), be taking a stable dose for at least 4 weeks before study start 8. If taking a medication(s) other than an antidiabetic that might affect blood glucose level, be taking a stable dose for at least 4 weeks before study start 9. Have a thyroid-stimulating hormone level on laboratory testing at screening that is within the reference range provided by the central laboratory. If the patient is taking thyroid hormone, the dose must have been stable for at least 6 weeks before study start 10. Be willing to discontinue, for the duration of the study, all herbal medication taken for the treatment of diabetes 11. Have a fasting serum C-peptide > 0.26 nmol/L (> 0.8 ng/mL; > 260 pmol/L) on laboratory testing at screening 12. Female patients must not be pregnant, not planning to become pregnant during the course of the study, and not lactating. Women of childbearing potential must have a negative serum β-human chorionic gonadotropin pregnancy test on laboratory testing at screening 13. If of childbearing potential (or having partner[s] of childbearing potential), must be willing to use an adequate method of contraception and not become pregnant (or have partner[s] become pregnant) for the duration of the study. Adequate contraceptive methods include, but are not limited to, oral contraceptives (stable use for 2 or more cycles before screening); intrauterine devices; Depo-Provera; Norplant System implants; bilateral tubal ligation; vasectomy; condom or diaphragm plus either contraceptive sponge, foam, or jelly; and abstinence 14. Have an HbA1c level ≥ 7.0% and ≤ 10.0% 15. Be drug-treatment naïve, or treated with a stable dose of pioglitazone or rosiglitazone, or treated with a stable dose of any other oral hypoglycemic agent (OHA) as monotherapy at the time of the Screening Visit (Visit 1): ○ Drug-treatment naïve means never having received an OHA or parenteral medication (insulin or GLP-1 analogue) or, if having received an OHA or parenteral medication, been off said OHA or parenteral medication for a minimum of 6 weeks (12 weeks for pioglitazone or rosiglitazone) before Visit 1 ○ Stable dose of pioglitazone or rosiglitazone means a minimum of 12 weeks ○ Stable dose of any other OHA as monotherapy means a minimum of 6 weeks 16. Be willing to refrain from donating blood during the study and for up to 1 month after completing the study Between Visits 1 and 2: 17. Patients who switch to pioglitazone or whose dosage of pioglitazone is increased during the screening period must have an FPG level ≤ 270 mg/dL (15 mmol/L) before Visit 2 At Visit 2: 18. Have been on a stable dosage of pioglitazone, 30 to 45 mg/d, as monotherapy for 8 or 12 weeks, depending on OHA therapy leading up to Visit 1 (Screening) At the Randomization Visit (Visit 4): 19. Have an HbA1c level ≥ 7.0% and ≤ 10.0% (measured at Visit 3) 20. Have an FPG level ≤ 270 mg/dL (15 mmol/L) (measured at Visit 3). The test can be repeated once if the initial result is felt to be inaccurate or not representative of the patient’s usual value |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will not be eligible to participate in the study: 1. Currently taking more than one OHA 2. Have been treated as an outpatient with insulin, a GLP-1 analogue, or a DPP4 inhibitor within 6 weeks of the Screening Visit (Visit 1) 3. Have type 1 diabetes mellitus, maturity-onset diabetes of the young, insulin-requiring T2DM, other unusual or rare forms of diabetes mellitus, history of diabetic ketoacidosis, or clinically relevant late diabetic complications 4. Have elevated blood glucose levels owing to medical treatment or to a concurrent medical condition other than T2DM 5. Have skin lesions (eg, discoloration, swelling, atrophy, ulceration), edema states, or diabetic foot ulcers considered medically important by the Investigator 6. Have a history of epilepsy, not including childhood febrile seizures 7. Have a history of hypoglycemic episode requiring glucose, glucagon, orange juice, etc administered by a second person during the 6 months before the Screening Visit (Visit 1) 8. Have a history of hyperosmolar, hyperglycemic, or nonketotic syndrome during the 6 months before the Screening Visit (Visit 1) 9. Have had a stroke, myocardial infarction, symptomatic coronary artery disease, angina, or arrhythmia within 4 weeks before the Screening Visit (Visit 1) or a history of congestive heart failure (class I to class IV according to the New York Heart Association functional classification system) 10. Have a history of or risk factors for acute pancreatitis or exacerbation of chronic pancreatitis 11. Have a systolic blood pressure (SBP) ≥ 160 mm Hg or < 90 mm Hg and/or diastolic blood pressure (DBP) ≥ 100 mm Hg or < 50 mm Hg at the Screening Visit (Visit 1). The measurement at the Screening Visit (Visit 1) can be repeated if the initial reading is felt to be inaccurate or unrepresentative of the patient’s usual blood pressure value 12. Have had gastrointestinal surgery for obesity (including bypass, gastroplasty, and banding procedures) within 1 year before the Screening Visit (Visit 1) or have plans to have such surgery or procedures for the removal of excess fatty tissue during the course of the study 13. Have started a weight-loss regimen within 4 weeks of the Screening Visit (Visit 1), either on one’s own or by participating in a commercial behavior modification/diet program or by taking a medication for weight reduction 14. Currently taking an antipsychotic medication (except prochlorperazine as needed for nausea), have taken systemic glucocorticoids at a dose > 5 mg of prednisone or equivalent daily within the 2 weeks before the Screening Visit (Visit 1), or currently taking products intended to stimulate appetite. (See the Study Reference Manual for prednisone equivalence of other glucocorticoids) 15. Have a history of cancer other than treated basal-cell or squamous-cell carcinoma of the skin. (Note: Patients with a history of cancer are allowed to participate provided that the malignancy has been in complete remission for at least 5 years before the Screening Visit [Visit 1]. Complete remission is defined as the disappearance of all signs of cancer in response to treatment) 16. Have a history of infection with human immunodeficiency virus, or have serologic evidence of current infection (acute or chronic) with hepatitis B virus or hepatitis C virus as determined by the central laboratory at Visit 1 17. Have a history of alcohol or substance abuse in the prior 2 years or an eating disorder diagnosed in the prior 5 years 18. Have total bilirubin concentration above the upper limit of normal (ULN) (unless associated with an elevated indirect bilirubin concentration typical of Gilbert syndrome), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the ULN, or alkaline phosphatase > 1.5 times the ULN from the Screening Visit (Visit 1) clinical laboratory results 19. Have hemoglobin level < 11 g/dL (< 110 g/L) from the Screening Visit (Visit 1) clinical laboratory results 20. Have an estimated glomerular filtration rate (GFR) < 50 mL/min/1.73 m2 per the Modification of Diet in Renal Disease (MDRD) equation at the Screening Visit (Visit 1), as provided by the central laboratory 21. Have received treatment with any investigational product or participated in any investigational study within 30 days or 5 half-lives of the investigational product, whichever is longer, before the Screening Visit (Visit 1) 22. Have been randomized in a previous investigational study of dutogliptin 23. Be an employee or a relative of an employee of the study center 24. Have a history of hypersensitivity reaction to pioglitazone, rosiglitazone, glimepiride, or DPP4 inhibitors 25. Have any condition, disease, disorder, or clinically significant laboratory abnormality that, in the opinion of the PI, would jeopardize the patient’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) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Multicenter, fixed-dose trial. |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |