| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| 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 |
| The primary objective of this study is to test the hypothesis that exenatide (injected twice daily) is non-inferior to premixed human insulin aspart (injected twice daily) in terms of glycemic control, and superior to premixed human insulin aspart in terms of hypoglycemia incidence, when given in combination with metformin to patients with Type 2 diabetes who failed to achieve glycemic control with metformin alone. |
|
| E.2.2 | Secondary objectives of the trial |
secondary objectives are to compare the two injectable treatment regimens with respect to:
•proportion of patients achieving HbA1c targets of < 6.5% (DDG target)
•secondary analysis of percentage of patients with at least one treatment-emergent hypoglycemic episode during a treatment period of 26 weeks.
•Incidence and rate of nocturnal hypoglycemia
•Blood glucose control as assessed by self-measured 7-point blood glucose profiles
•Blood lipid levels
•Anthropometric measures, i.e. BMI, body weight, and waist circumference
•Patient reported treatment satisfaction and quality of life, as measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Quality of Life Questionnaire SF-12 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Present with Type 2 diabetes as defined by the World Health Organization (WHO) (refer to Protocol Attachment GWBN.3).
[2] Have been treated with diet and exercise and a stable, maximally tolerated dose (in the opinion of the investigator) of immediate-release metformin or extended-release metformin, or the combination of metformin (any dosage) with sulfonylurea/meglitinides for at least 3 months prior to Visit 1, and in the opinion of the investigator, require further intensification of their metabolic treatment.
[3] Have not received thiazolidinediones, or alpha-glucosidase inhibitors for longer than 2 weeks within 3 months prior to screening, and have not received any insulin formulation for more than 14 days other than in emergency situations and within 14 days prior to Visit 1.
[4] Have a HbA1c ≥ 6.5% and ≤ 10.0%, according to the central laboratory measurement performed at Visit 1.
[5] Are ≥ 18 years and ≤ 90 years of age.
[6] Have a body mass index (BMI) of ≥ 25 kg/m2 and ≤ 40 kg/m².
[7] Are willing to perform blood glucose self-measurements and to use the patient diary as required for this protocol.
[8] Inclusion criterion [8] applies to females of child-bearing potential (not surgically sterilized and between menarche and 1 year post menopause) only:
Are not breastfeeding, test negative for pregnancy at the time of Visit 1, intend not to become pregnant during the study and agree to use a reliable method of birth control during the study (for example, use of oral contraceptives or Norplant; a reliable barrier method of birth control such as intrauterine implants with contraceptive jelly; partner with vasectomy; or abstinance).
|
|
| E.4 | Principal exclusion criteria |
[9] Have Type 1 diabetes or known latent autoimmune diabetes in adults (LADA).
[10] Have active symptomatic proliferative diabetic retinopathy or any other condition excluding a rapid lowering of HbA1c.
[11] Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to Screening (Visit 1).
[12] Have known history of metabolic acidosis.
[13] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransaminase/serum glutamic pyruvic transaminase (ALT/SGPT) greater than three times the upper limit of the reference range as defined by the central laboratory.
[14] Have known hemoglobinopathy or chronic anaemia that is clinically significant as defined by the central laboratory’s reference range
[15] Patients have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
[16] Have a history of renal transplantation, have end-stage renal disease or severe renal impairment (creatinine clearance < 30 mL/min), or are currently receiving renal dialysis or have serum creatinine ≥1.5 mg/dL (132 micromol/L) for males and ≥1.3 mg/dL (110 micromol/L) for females, as determined by the central laboratory.
[17] Have cardiac disease that is Class III or IV, according to the New York Heart Association criteria (Protocol Attachment GWBN.4).
[18] Have congestive heart failure requiring pharmacologic treatment.
[19] Have had more than one episode of severe hypoglycemia within 6 months prior to Visit 1, with severe hypoglycemia defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions (ADA 2005, Protocol Attachment GWBN.5).
[20] Have a known allergy or hypersensitivity to insulin, exenatide, or percipients contained in these agents.
[21] Have characteristics contraindicating metformin use, according to product-specific label.
[22] Are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
[23] Have severe gastrointestinal disease, including gastroparesis.
[24] Have used any prescription drug to promote weight loss within 3 months prior to screening.
[25] Are investigator site personnel directly affiliated with this study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[26] Are Lilly or Amylin employees.
[27] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[28] Have previously completed or withdrawn from this study or any other study investigating exenatide or GLP-1 analogs.
[29] Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
[30] 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 planned treatment period will be 26 +/- 2 weeks. The study treatment will end with visit 8 (final visit). Study medication will be discontinued, the patient has to be referred to an appropriate diabetes treatment regimen. |
|
| 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 | 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) | 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 50 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
|
| last visit of the last subject undergoing the trial |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 6 |
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