E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053247 |
E.1.2 | Term | Insulin-requiring type 2 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 Study BIAC is to test the hypothesis that in patients with Type 2 diabetes who are treated with basal insulin and continuing their prestudy therapeutic regimen of Oral Antihyperglycemic Medications (OAMs), LY2605541 injected once daily in the morning results in lower fasting blood glucose (FBG) levels at endpoint compared with insulin glargine injected once daily in the morning for up to 12 weeks. |
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E.2.2 | Secondary objectives of the trial |
• To compare the change from baseline of FBG levels at endpoint between LY2605541 and insulin glargine. • To assess the two LY2605541 dose algorithms. • To assess the safety and tolerability of LY2605541, including generation of antibodies to LY2605541. • To compare the proportion of patients experiencing hypoglycemia and the rate of hypoglycemia, adjusted per 30 days, between LY2605541 and insulin glargine. • To compare the 8-point self-monitored blood glucose (SMBG) profiles between LY2605541 and insulin glargine. • To characterize within-patient and between-patient variability of FBG for patients receiving LY2605541. • To compare the baseline to endpoint change in hemoglobin A1c (HbA1c) to assess glycemic control between LY2605541 and insulin glargine. • To compare the daily basal insulin dose between LY2605541 and insulin glargine. • To evaluate the pharmacokinetics (PK) of LY2605541 after multiple doses in patients with type 2 diabetes mellitus (T2DM). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Sample Banking Addendum I2R-MC-BIAC(1): A Phase 2 Study of LY2605541 Compared with Insulin Glargine in the Treatment of Type 2 Diabetes Mellitus
2009 - 09 - 25
Eli Lilly and Company has established a program, Combined Specimen Banking (CSB), to bank samples (collectively called Banked Samples) from patients enrolled in studies sponsored by Eli Lilly and Company. The Banked Samples are collected and banked for research to identify the genes (DNA) associated with diseases and/or response to clinical trial medication or other medication taken during the trial. |
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E.3 | Principal inclusion criteria |
[1] Have type 2 diabetes mellitus (T2DM) for at least 1 year based on the World Health Organization (WHO) classification, previous diagnosis, and the investigator’s assessment. [2] Are ≥18 years of age. [3] Have been receiving at least 1 of the following oral antihyperglycemic medications (OAMs) in combination with once daily insulin glargine or once daily NPH for at least 3 months immediately prior to the study. The maximum daily basal insulin dose permitted prior to the study is 1.0 U/kg. Doses of any OAMs are required to have been stable for the 6 weeks prior to Screening visit, and at least 1 of the OAMs must be dosed at or above the dose defined below: • Metformin, 1500 mg/day • Sulfonylureas, one half the maximum daily dose according to the local package insert [4] Have a hemoglobin A1c (HbA1c) value ≤10.5%, as measured by a central laboratory before Randomization. [5] Have a BMI ≥19 and ≤45 kg/m2. [6] As determined by the investigator, are capable and willing to do the following: • Prepare and inject the study insulin with a syringe while continuing to use the prestudy OAMs specified in Inclusion Criterion [3]; • perform self-monitored blood glucose (SMBG); • complete the study diary as required for this protocol; • be 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 receive telephone calls between visits. [7] Have access to a telephone. [8] Be able to read. [9] Have refrigeration in the home. [10] Give written informed consent to participate in this study in accordance with local regulations. [11] Are women of childbearing potential (women not surgically sterilized and between menarche and 2 years postmenopause) who test negative for pregnancy at the time of Screening visit and Randomization based on a urine pregnancy test and agree to use a reliable method of birth control (for example, abstinence from heterosexual intercourse, oral contraceptives, Norplant®, or contraceptive transdermal patch; a reliable barrier method of birth control; intrauterine device; or partner with vasectomy) during the study and until the time they complete the follow-up visit. |
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E.4 | Principal exclusion criteria |
[12] Have received scheduled, long-term short-acting or rapid-acting or premixed insulin therapy within the past 6 months. Patients who have received short- or rapid-acting insulin as part of short-term insulin therapy (for example, during gestational diabetes, during an acute hospitalization/illness) or occasional use will be allowed to participate in this study. Occasional use (for example, used to treat acute hyperglycemia) shall be defined as less than daily administration of not more than 1 dose per day of short- or rapid acting insulin. [13] Have taken any glucose-lowering medications not included in Inclusion Criterion [3] and Exclusion Criterion [12] (for example, acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide) in the 3 months prior to Screening visit. [14] Are currently taking, or have taken within the 3 months preceding Screening visit, prescription or over-the-counter medications to promote weight loss. [15] Are currently participating in a weight loss program, or plan to do so during the course of the study. [16] Have received treatment within the 6 months preceding Screening visit with any antibody-based therapy. [17] 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 Screening visit. [18] Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness. [19] Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months. [20] 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 normal at Screening visit). [21] Have a history of renal transplantation, are currently receiving renal dialysis, or have a Screening visit creatinine >2.0 mg/dL (177 μmol/L). (For patients on metformin therapy, see Exclusion Criterion [22].) [22] For patients using metformin: have a serum creatinine concentration that contraindicates use of metformin according to the country-specific metformin product label; have known metabolic or lactic acidosis; have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis; or 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. [23] Have cardiac disease with functional status that is Class III or IV. [24] Have electrocardiogram (ECG) abnormalities obtained at Screening visit that, in the opinion of the investigator, are clinically significant with regard to the patient’s participation in the study. These include QTc prolongation (Bazett’s corrected QTc interval, QTcB) of >450 msec in male patients or >470 msec in female patients, or abnormally wide QRS complexes (resulting from bundle branch blocks, intraventricular conduction delays, or pacemakers). [25] Have a malignancy other than basal cell or squamous cell skin cancer and have not yet been treated, are currently being treated, or were diagnosed less than 5 years ago. [26] Have fasting triglycerides >500 mg/dL. [27] Have significant abnormalities (significant would include laboratory deviations requiring acute medical intervention or further medical evaluation) in laboratory results, including serum chemistries, hematology, and urinalysis, and any clinical information that, in the judgment of a physician, should preclude a patient’s participation at study entry. [28] Have known diabetic autonomic neuropathy. [29] Have known hypersensitivity or allergy to any of the study insulins or their excipients. [30] Have had a blood transfusion or severe blood loss within 3 months prior to Screening visit or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c methodology. [31] Have had any other illness or condition (including known drug or alcohol abuse or psychiatric disorder) within the 6 months preceding Screening visit that precludes the patient from following and completing the protocol or could increase their risk for hypoglycemia, according to the investigator’s judgment. [32] Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night), in the investigator’s opinion. [33] Women who are breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure is the fasting blood glucose at endpoint, as measured by the 8-point self-monitored glucose profiles. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |