| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067584 |
| E.1.2 | Term | Type 1 diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 LY2963016 (QD) is noninferior to Lantus (QD), as measured by change in HbA1c from baseline to 24 weeks, when used in combination with premeal insulin lispro administered thrice a day (TID). |
|
| E.2.2 | Secondary objectives of the trial |
To compare safety of LY2963016 relative to Lantus (eg, incidence of anti-insulin antibodies, hypoglycemia, adverse events [AEs]) when used in combination with premeal insulin lispro.
To compare LY2963016 relative to Lantus for other efficacy variables .
To compare LY2963016 relative to Lantus with regard to intrapatient bloodglucose (BG) variability, basal and prandial (separately and as total daily) insulin dose, and weight when used in combination with premeal insulin lispro.
To test hypothesis that Lantus is noninferior to LY2963016 as easured by change in HbA1c from baseline to 24 weeks, when used in combination with premeal insulin lispro.
To compare patient-reported outcomes (PRO) as measured by responses to the Adult Low Blood Sugar Survey and the Insulin Treatment Satisfaction Questionnaire between LY2963016 and Lantus. |
|
| 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 |
The sub-study is included in section 10.4.2. "Pharmacogenetic Testing" of original protocol with code:I4L-MC-ABEB & protocol date: 22 FEB 2011.
It describes a blood sample collection for pharmacogenetic analysis. Samples will be stored and analysis may be performed on genetic variants thought to play a role in diabetes susceptibility or progression (eg, β-cell function, insulin sensitivity), characterization of patients’ responsiveness to LY2963016 or Lantus, or diabetes-related metabolic abnormalities (eg, lipid accumulation/metabolism, inflammation), including, but not limited to, MHC, INS, and PTPN22, to evaluate their association with observed response to LY2963016 or Lantus. |
|
| E.3 | Principal inclusion criteria |
[1] Have T1DM based on the disease diagnostic criteria (World Health
Organization [WHO] Classification)
[2] Aged ≥18 years
[3] Have duration of diabetes ≥1 year.
[4] Have HbA1c ≤11.0 %
[5] On basal-bolus insulin therapy for at least 1 year (basal insulin must be QD injection of NPH, Lantus, or detemir and combined with mealtime injections of human regular insulin, or insulin analog lispro, aspart, or glulisine).
[6] Have body mass index (BMI) ≤35 kg/m2.
[7] As determined by the investigator, are capable and willing to do the
following:
o perform SMBG
o complete patient diaries as required for this protocol
o use the insulin injection device(s) according to the instructions
provided
o are receptive to diabetes education
o comply with the required study insulins and study visits.
[8] Have given written informed consent to participate in this study in accordance with local regulations. |
|
| E.4 | Principal exclusion criteria |
[9] Exposure to a biosimilar insulin glargine.
[10] Excessive insulin resistance at entry into the study (total daily insulin dose [TDID] ≥1.5 U/kg).
[11] Have had more than one episode of severe hypoglycemia, as defined in Section 9.9 of the protocol, within 6 months prior to entry into the study.
[12] Have had more than one episode of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within 6 months prior to entry into the study.
[13] Have known hypersensitivity or allergy to any of the study insulins (insulin glargine or insulin lispro) or to excipients of the study insulins.
[14] Are pregnant, 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.
[15] Women who are breastfeeding.
[16] Have taken any oral antihyperglycemic medications (OAMs) within 3 months prior to Visit 1.
[17] 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.
[18] Have received treatment with pramlintide or with continuous subcutaneous insulin infusion within 3-months prior to Visit 1.
[19] Have congestive heart failure Class III and IV
[20] Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 2.5 times the upper limit of the reference range, as defined by the central laboratory); or albumin value remarkably above or below the normal reference range, as defined by the central laboratory.
[21] Have any active cancer, or a personal history of cancer within the previous 5 years (except basal-cell cancer or carcinoma in situ).
[22] Have presence of clinically significant gastrointestinal disease (eg,
gastroparesis).
[23] Have a history of renal transplantation, or are currently receiving renal dialysis, or have creatinine greater than 2.0 mg/dL (177 mol/L).
[24] 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.
[25] 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.
[26] Have an irregular sleep/wake cycle (eg, patients who sleep during the day and work during the night).
[27] Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the patient from following and completing the protocol.
[28] 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.
[29] Are Lilly employees.
[30] Have previously completed or withdrawn from this study after having signed the ICD.
[31] Are currently enrolled in, or discontinued from within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device other than LY2963016, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Change in HbA1c from baseline to endpoint defined as the value at 24 weeks or last-postbaseline-observationcarried-
forward (LOCF). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- 7-point SMBG (expressed as plasma-equivalent glucose values obtained before each meal, after the
morning and mid-day meals, at bedtime, and at 3 am)
- Intrapatient variability as measured by the standard deviation (SD) of the FBG
- Change in HbA1c from baseline to 6 and 12 weeks or LOCF
- Percentage of patients with HbA1c <7%, percentage of patients with HbA1c ≤6.5%
- Total, insulin, basal insulin, and insulin lispro doses
- Weight
- Patient-reported outcomes as reflected in responses to ALBSS and ITSQ. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 6, 12, 24, 36 and 52 weeks of treatment |
|
| 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 | No |
| 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 | Yes |
| 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) | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| 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 | No |
| 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 |
| Belgium |
| Brazil |
| Germany |
| Greece |
| Hungary |
| Japan |
| Mexico |
| Poland |
| Romania |
| Russian Federation |
| Slovakia |
| United States |
|
| 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
| |
| 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 | 7 |
| 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 | 8 |
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