| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type II diabetes mellitus |
|
| 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 | 10063624 |
| E.1.2 | Term | Type II diabetes mellitus inadequate control |
|
| 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 test the hypothesis that, in T2DM, a basal bolus regimen containing analog insulin lispro protamine suspension provides noninferior glycemic control to a basal bolus regimen containing analog insulin glargine, when these basal insulins are injected once daily together with insulin lispro injected 2-3 times daily.
Glycemic control will be assessed by the change of HbA1c from baseline to 24 weeks, |
|
| E.2.2 | Secondary objectives of the trial |
To compare the efficacy, safety of insulin lispro protamine suspension and glargine when used in a basal bolus regimen together with insulin Lispro in relation to:
• Change in HbA1c at 12 weeks and at 24 weeks;
• percentage of patients with HbA1c <7.0% and HbA1c ≤6.5% at 24 weeks;
• 7-point self-monitored blood glucose (SMBG) profile at 24 weeks;
• glycemic variability at 24 weeks;
• to compare the safety of insulin lispro suspension and glargine when used in a basal bolus regimen together with insulin lispro in relation to:
o the incidence of self-reported hypoglycemic episodes
o absolute body weight (kg) and incremental weight change from baseline to 24 weeks
o treatment-emergent adverse events (TEAEs);
• to compare total daily insulin dose and number of injections at 24 weeks.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following criteria:
1. Have type 2 diabetes mellitus (T2DM; World Health Organization [WHO] classification, Protocol Attachment 2) for at least 1 year.
2. Are ≥18 years old.
3. Have been receiving oral antihyperglycemic medications (OAMs), with insulin, for at least 3 months immediately prior to the study and have been on stable doses of at least 2 of the following OAMs for the 6 weeks prior to Visit 1, at or above the doses defined in the following table:
Oral Antihyperglycemic Medication (OAM)
Minimum Dose
Metformin 1500 mg/day
Sulfonylureas;
Dipeptidyl peptidase-IV (DPP-IV) inhibitors 1/2 the maximum daily dose, according to the local package insert.
Thiazolidinediones (TZDs) 30 mg/day pioglitazone or 4 mg/day rosiglitazone
The OAMs also must have been used in accordance with the product label. (Note: Combination treatments of the OAMs listed above are acceptable if they meet the above criteria. For example, Avandamet® [rosiglitazone maleate and metformin hydrochloride] would cover the categories of a thiazolidinedione (TZD) and metformin.)
4. Have a hemoglobin A1c (HbA1c) ≥7.5% and ≤11.0%, as measured by a central laboratory before Visit 2.
5. Body mass index (BMI) ≥25 and ≤45 kg/m2.
6. As determined by the investigator, are capable and willing to do the following:
• use the insulin injection device according to the instructions provided;
• perform self monitoring of blood glucose (SMBG);
• complete the study diary as required for this protocol;
• are receptive to diabetes education, including continuing their prestudy diet and activity levels, or following dietary advice recording as requested in the protocol;
• comply with the required study visits and willing to receive regular telephone calls between visits.
• Have given written informed consent to participate in this study in accordance with local regulations. |
|
| E.4 | Principal exclusion criteria |
7. Have taken any glucose-lowering medications not included in Inclusion Criterion [3] (for example, acarbose, miglitol, pramlintide, exenatide) in the past 3 months before Visit 1.
8. Have had more than 1 episode of severe hypoglycemia, as defined in the Abbreviations and Definitions section of the protocol, within 6 months prior to entry into the study, or is currently diagnosed as having hypoglycemia unawareness.
9. Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
10. Are pregnant or intend to become pregnant during the course of the study or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable.
11. Women who are breastfeeding.
12. Have cardiac disease with functional status that is Class III or IV (see Protocol Attachment.3);
13. Have a history of renal transplantation or are currently receiving renal dialysis or creatinine >1.3 mg/dL (115 µmol/L) or have a GFR according to Cockcroft-Gault < 60ml/min.
14. Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (alanine transaminase [ALT], or aspartate transaminase [AST] greater than 2 times the upper limit of the reference range, as defined by the local laboratory) or have albumin value above or below the normal reference range, as defined by the local laboratory.
15. Patients with a malignancy other than basal cell or squamous cell skin cancer who have not yet been treated, are currently being treated, or who were diagnosed less than 5 years ago.
16. Have 1 of the following concomitant diseases: presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease or any other serious disease considered by the investigator to be exclusionary.
17. Have known hypersensitivity or allergy to any of the study insulins or their excipients.
18. Have had a blood transfusion or severe blood loss within 3 months prior to Visit 1 or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c methodology.
19. Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular, and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding Visit 1.
20. Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night), in the investigator’s opinion.
21. Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the patient from following and completing the protocol, according to the investigator’s judgment.
22. 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.
23. Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
24. Are Lilly employees.
25. Have previously completed or withdrawn from this study after having signed the informed consent document (ICD). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) | |
| 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
| Information not present in EudraCT |
| 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 | 45 |
| 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 |
|
| 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
| |
| 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 | 5 |
| 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 | 7 |
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