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 | 10012601 |
E.1.2 | Term | 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 |
The primary objective of this study is to test the hypothesis that switching to exenatide and metformin is non-inferior to adding exenatide to sitagliptin and metformin, as measured by a change in HbA1c from baseline to endpoint (Week 16), in patients with type 2 diabetes experiencing inadequate glycemic control with sitagliptin plus metformin. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to compare treatment arms in term of: • proportion of patients achieving HbA1c ≤7.0%, <7.0% and ≤6.5% at endpoint (Week 16) • change from baseline to endpoint (Week 16) in fasting serum glucose (FSG) • change from baseline to endpoint (Week 16) in body weight • change from baseline to endpoint (Week 16) in waist circumference and waist-to-hip ratio • 7-point self-monitored blood glucose (SMBG) profiles and mean blood glucose (BG) measurement based on 7-point SMBG • change from baseline to endpoint (Week 16) in serum lipids (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], fasting triglycerides, calculated low-density lipoprotein cholesterol [LDL-C]) • safety and tolerability (including incidence of hypoglycemic events) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Present with type 2 diabetes as defined by the WHO criteria. [2] Aged between 18 and 75 years of age, inclusive. [3] Patients have been treated with a stable dose of the following for at least 3 months prior to screening: • 100 mg/day sitagliptin and • ≥1500 mg/day metformin, or maximum tolerated dose (extended-release or immediate-release). [4] Have inadequate glycemic control as evidenced by an HbA1c between 7.1% and 10%, inclusive. [5] Have a body mass index (BMI) ≥20kg/m2 and <45 kg/m2, and a history of stable body weight. [6] This inclusion criterion applies to females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only: • Are not breastfeeding. • Test negative for pregnancy at the time of screening based on a blood serum pregnancy test. • Intend not to become pregnant during the study. • Have practiced a reliable method of birth control for at least 6 weeks prior to screening. • Agree to continue to use a reliable method of birth control during the study, as determined by the investigator. |
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E.4 | Principal exclusion criteria |
[7] Are investigator site personnel directly affiliated with this study and/or their immediate families. [8] Are Lilly or Amylin employees. [9] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [10] Have previously completed or withdrawn from this study or any other study investigating exenatide. [11] Have had poorly controlled blood pressure within the last 4 weeks. [12] Have a known allergy or hypersensitivity to exenatide, sitagliptin or excipients contained in exenatide or sitagliptin. [13] Have characteristics contraindicating metformin, exenatide or sitagliptin use, according to product-specific label. [14] Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study. [15] Have a history of renal transplantation; or are currently receiving renal dialysis; or have serum creatinine ≥1.5 mg/dL (132 μmol/L) for males and ≥1.2 mg/dL (110 μmol/L) for females; or have an estimated creatinine clearance of <50 mL/min based on the standard Cockcroft-Gault formula. [16] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, ALT, or SGPT greater than 2.5 times the upper limit of the reference range. [17] Are known to have active proliferative retinopathy. [18] Patients with a history of, or current, acute or chronic pancreatitis. [19] Used drugs for weight loss within 1 month of screening. [20] Are currently treated with any of the following excluded medications: o Thiazolidinediones within 3 months of screening. o Sulfonylurea o Dipeptidyl peptidase-4 [DPP-4] inhibitors, with the exception of sitagliptin o Meglitinide derivatives o Alpha-glucosidase inhibitors o Exogenous insulin within the 3 months prior to screening. o Drugs that directly affect gastrointestinal motility o Systemic corticosteroids o Any other oral antidiabetic (OAD) agent [21] Have an active or untreated malignancy, or have been in remission from clinically significant malignancy for less than 5 years. [22] Have had an organ transplant. [23] Have any other condition that renders them unable to understand the nature, scope, and possible consequences of the study or precludes them from following and completing the protocol, in the opinion of the investigator. [24] Fail to satisfy the investigator of suitability to participate for any other reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure is change in HbA1c from baseline to endpoint (Week 16). |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |