| 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 | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| 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, for adult patients with type 2 diabetes mellitus (T2DM) who are taking 2 or more oral antihyperglycemic medications (OAMs) without insulin and have inadequate glycemic control, basal analog insulin lispro protamine suspension, injected once or twice daily, is noninferior to basal analog insulin detemir, injected once or twice daily, with regard to glycemic control as measured by change in hemoglobin A1c (HbA1c) from baseline to 24 weeks. The noninferiority margin is 0.4%. |
|
| E.2.2 | Secondary objectives of the trial |
•Insulin lispro protamine suspension (ILPS) is noninferior to detemir as measured by standard deviation of fasting blood glucose (FBG) as a measure of intrapatient glycemic variability
•ILPS is noninferior to detemir as measured by change in absolute body weight (noninferiority margin of 1.5 kg) from baseline to 24 weeks.
•ILSP is superior to detemir with regard to glycemic control as measured by change in HbA1c from baseline to endpoint.
These objectives will be tested in the order listed above. This “gatekeeping” approach requires all previous tests to demonstrate a statistically significant result at the 0.05 level before conducting the next test in the list.
Additional secondary objectives of the study are to compare the efficacy and safety of the 2 basal insulin analog treatments when used in combination with 1 or more OAMs. Details see protocol |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Have type 2 diabetes mellitus (T2DM; World Health Organization [WHO] classification, Protocol Attachment IOOY.2) for at least 1 year.
[2] Are >= 18 years old.
[3] Have been receiving oral antihyperglycemic medications (OAMs), without 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:
Metformin, Minimum Dose: 1500 mg/day
Sulfonylureas and Dipeptidyl peptidase-IV (DPP-IV) inhibitors1, Minimum Dose: 1/2 the maximum daily dose, according to the local package insert.
Thiazolidinediones, Minimum Dose: 30 mg/day pioglitazone or 4 mg/day rosiglitazone
The OAMs also must be used in accordance with the product label and be approved for use with insulin in the patient’s country. (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 <=10.0%, 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;
• inject insulin while continuing to use the prestudy regimen of OAMs specified in Inclusion Criterion [3];
• 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 simple dietary advice as appropriate;
• comply with the required study visits and willing to receive regular telephone calls between visits.
[7] Have given written informed consent to participate in this study in accordance with local regulations. |
|
| E.4 | Principal exclusion criteria |
[8] Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks.
[9] Have taken any glucose-lowering medications not included in Inclusion Criterion [3] (for example, acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide) in the past 3 months before Visit 1.
[10] 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.
[11] Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
[12] 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.
[13] Women who are breastfeeding.
[14] Have cardiac disease with functional status that is Class III or IV; or, if taking a TZD, have congestive heart failure of a less severe functional status, which would contraindicate in their respective country the use of TZD alone or in combination with insulin.
[15] Have a history of renal transplantation or are currently receiving renal dialysis or creatinine >2.0 mg/dL (177 µmol/L).
[16] 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.
[17] 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.
[18] 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.
[19] Have known hypersensitivity or allergy to any of the study insulins or their excipients.
[20] 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.
[21] 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.
[22] Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night), in the investigator’s opinion.
[23] 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.
[24] 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.
[25] 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.
[26] Are Lilly employees.
[27] Have previously completed or withdrawn from this study after having signed the informed consent document (ICD).
[28] For patients using metformin, have a serum creatinine concentration that contraindicates use of metformin according to the country-specific metformin product label.
[29] For patients using metformin, have known metabolic or lactic acidosis.
[30] For patients using metformin, have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
[31] For patients using metformin, have had a radiologic contrast study within 48 hours prior to entry in the study or plan to have such a procedure or surgery performed during the study. |
|
| 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) | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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