E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 evaluate the safety and tolerability of vildagliptin (50 mg qd or 100 mg qd) versus placebo in patients with T2DM and moderate renal insufficiency over 24 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
Exploratory objective(s) • To explore the relationship between renal function and concentration levels of vildagliptin and its metabolites after repeated doses of vildagliptin (50 mg qd and 100 mg qd) in patients with T2DM and moderate renal insufficiency. • To explore the efficacy of vildagliptin (50 mg qd or 100 mg qd) versus placebo in patients with T2DM and moderate renal insufficiency by assessing the hemoglobin A1C (HbA1c ) and fasting plasma glucose (FPG) reduction from baseline after 24 weeks of treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age in the range of 18-85 years inclusive at visit 1 2. Patients with T2DM either untreated (defined as not taking anti-diabetic therapy for at least 8 weeks prior to visit 1) or treated with anti-diabetic therapy defined as sulfonylurea, AGIs, TZDs, insulin, and metiglinides as monotherapy or combination therapy for at least 8 weeks prior to visit 1 3. Patients treated with anti-diabetic therapy must be on a stable dose for the past 4 weeks prior to visit 1 (stable insulin therapy is defined as ± 20% of total daily units) 4. GFR estimated by the Cockcroft-Gault formula of ≥ 30 and < 50 mL/min at visit 1 5. HbA1c of ≥ 6.5 and ≤ 10 % at visit 1 6. Body weight < 120 kg and body mass index (BMI) 18-42 kg/m2 at visit 1 7. Male, non-fertile female or female of childbearing potential using a medically approved birth control method by the country health authorities that may include: • A non-fertile female is defined as: post menopausal (12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mLU/m); 6 weeks post bilateral oophorectomy with or without hysterectomy; post hysterectomy; or sterilized by tubal ligation • A female of childbearing potential is defined as any woman physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means • Medically approved birth control methods may include: hormonal contraceptives, intrauterine contraceptive device (IUD), and double-barrier contraception. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception • Reliable contraception should be maintained throughout the study 8. Agreement to continue their current diet/exercise regimen and sulfonylurea, AGI, TZD, insulin, or metiglinide therapy throughout the duration of the study or to remain untreated if patient is not taking anti-diabetic therapy, unless otherwise instructed by the trial’s physician 9. Written informed consent to participate in the study and ability to comply with all study requirements
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E.4 | Principal exclusion criteria |
1. FPG ≥ 270 mg/dL (≥15 mmol/L) 2. Pregnant or lactating female 3. A history of: • Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g. Cushing’s syndrome and acromegaly • Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months 4. Patients that have been enrolled in a vildagliptin clinical trial or other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within six months prior to visit 1 5. History of renal transplant at any time in the past 6. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study 7. Any pre-existing lower extremity diabetic skin ulcer 8. Patients taking TZDs with established peripheral edema 9. Congestive heart failure (New York Heart Association (NYHA) class III-IV) 10. Any of the following within the past 6 months: • myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the clinical trial at the discretion of the investigator and/or local medical monitor); • unstable angina • coronary artery bypass surgery or percutaneous coronary intervention; • stroke 11. Any of the following ECG abnormalities: • Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation • second degree AV block (Mobitz 1 and 2) • third degree AV block • prolonged QTc (> 500 ms) 12. Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years 13. Liver disease such as cirrhosis or chronic active hepatitis B and C 14. Patients undergoing any method of dialysis (hemodialysis or peritoneal dialysis) or on the dialysis list at visit 1 15. Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study 16. Any of the following concomitant medications: • any anti-diabetic therapy other than sulfonylureas, AGIs, TZDs, insulin, and metiglinides within 8 weeks prior to visit 1 • chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1 • treatment with class Ia, Ib and Ic or III anti-arrhythmics • treatment with growth hormone or similar drugs • treatment with probenecid • treatment with any medication that is contraindicated in the renal impaired population (GFR < 50 mL/min: as calculated by Cockcroft-Gault formula) • treatment with any medication that is contraindicated in the use with sulfonylureas, AGIs, TZDs, insulin, and metiglinides • use of other investigational drugs within 30 days or 5 half-lives of the drug at visit 1, which ever is longer, unless local health authority guidelines mandate a longer period • treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e. cytostatic drugs) 17. Any of the following significant laboratory abnormalities: • Clinically significant thyroid stimulating hormone (TSH) outside of normal range at visit 1 • Clinically significant laboratory abnormalities at the opinion of the investigator • Patients with a serum albumin < 3.0 g/dL at visit 1 • Patients with a hemoglobin concentration < 9 g/dL at visit 1 • Elevated fasting triglycerides > 500 mg/dL at visit 1, confirmed by a repeat measure within 3 working days • Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at visit 1, confirmed by a repeat measure within 3 working days • Total bilirubin > 2 x ULN and/or direct bilirubin greater than the ULN at visit 1, confirmed by a repeat measure within 3 working days • History of spontaneous or drug induced muscle symptoms (not associated with exercise and/or physical activity), and/or elevated CPK (> 3 x ULN) confirmed by a repeat measure within 3 working days • A positive Hepatitis B surface test (antigen - HbsAg) • A positive Hepatitis C test (HCV antibodies) 18. History of active substance abuse (including alcohol and alcohol related hepatic disease) within the past 2 years 19. Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study 20. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of safety and tolerability of vildagliptin (50 mg qd or 100 mg qd) versus placebo in patients with T2DM and moderate renal insufficiency over 24 weeks of treatment.
The variables for the primary objectives include treatment emergent adverse events (including hypoglycemia events and events of special interest), serious adverse events. Biochemistry and hematology laboratory test results, ECG findings, and vital signs/body weight will also be assessed. |
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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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
multi-center, double-dummy |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |