E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10049746 |
E.1.2 | Term | Insulin-requiring type II diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 demonstrate that LY2605541 is noninferior to insulin glargine for the change in hemoglobin A1c(HbA1c) from baseline to 52 weeks of treatment in insulin-naïve patients with T2DM using a noninferiority margin (NIM) of 0.4%. |
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E.2.2 | Secondary objectives of the trial |
Gated:
to demonstrate that LY2605541 is superior to insulin glargine during 52 weeks for:
1.nocturnal hypoglyc. rate
2.patients with HbA1c <7.0% and no nocturnal hypoglycemia
3.HbA1c change from baseline
4.patients with HbA1c <7.0%
5.total hypoglycemia rate
6.fasting serum glucose (FSG) by laboratory measurement after 52 w
Non-Gated:
to compare the efficacy and safety of LY2605541 vs. insulin glargine for:
1.hypoglycemia rates and incidences
2.FSG by laboratory and SMBG
3.FBG intra-patient variability
4.weight change from baseline
5.6-point SMBG
6.pts. with HbA1c <7.0%
7.pts. with HbA1c ≤6.5%
8.pts. with HbA1c <7.0% and no nocturnal hypogl.
9.HbA1c change from baseline
10.HbA1c
11.insulin dose
12.number of dose adjustments to steady-state
13.lipid profile
14.antibodies to LY2605541
15.safety endpoints, SAE, vital signs, treatment exposure
16.health-state utility
17.ITSQ
18.low Blood Sugar Survey
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Have T2DM (per World Health Organization [WHO] Classification of Diabetes) not treated with insulin (Attachment 4).
[2] Are 18 years of age or older
[3] Have had diabetes for at least 1 year
[4] Have been receiving at least 2 OAMs for at least 3 months prior to the study. Two or more medications may be contained in 1 pill. Doses of any OAMs are required to have been stable for the 3 months prior to Visit 1 and at least 2 of the OAMs must be dosed at or above half the maximum daily dose allowed by local regulations or at the maximally tolerated dose of OAM.
• Note: OAMs must be used in accordance with the corresponding product label. Combination treatments of the OAMs are acceptable if they meet the above criteria. Combination medications should be counted as the number of individual components.
[5] Have HbA1c of 7.0% to 11.0%, inclusive, according to central lab at Visit 1
[6] Have BMI ≤45.0 kg/m2
[7] Are capable of, and willing to do, the following:
• Inject insulin with a vial and syringe and perform self blood glucose monitoring, and
• Record keeping as required by this protocol, as determined by the investigator
[8] Have given written informed consent to participate in this study in accordance with local regulations
[9] Have access to a telephone
[10] Have refrigeration in the home
[11] This inclusion criterion applies to females of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) only:
• Are not breastfeeding.
• Test negative for pregnancy at the time of screening (Visit 1) and randomization (Visit 3) based on a serum pregnancy test.
• Intend not to become pregnant during the study.
• Have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for at least 6 weeks prior to screening.
• Agree to continue to use a reliable method of birth control during the study, as determined by the investigator (and for 2 weeks following the last dose of study drug).
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E.4 | Principal exclusion criteria |
[12] Insulin therapy: have used insulin therapy ,anytime in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks. Insulin use of any duration during pregnancy is not considered an exclusion criterion.
[13] Concomitant medications: rosiglitazone, pramlintide, glucagon-like peptide 1 (GLP-1) receptor agonist (for example, exenatide, exenatide once weekly, or liraglutide) used concurrently or within 3 months prior to Visit 1 .
[14] Local OAM restrictions: for patients on OAMs, restrictions for cardiac, renal, and hepatic diseases, local product regulations must apply.
[15] Weight loss medications: are currently taking, or have taken within the 3 months preceding Visit 1, prescription or over-the-counter medications to promote weight loss.
[16] Severe hypoglycemia history: have had any episodes of severe hypoglycemia within 6 months prior to Visit 1.
[17] Diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar nonketotic coma (HHNKC): have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma in the past 6 months.
[18] Cardiovascular: have cardiac disease with functional status that is [NYHA] Class III or IV
[19] Renal: have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine ≥2 mg/dL (177 mol/L).
[20] Hepatic: have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements:
• total bilirubin ≥2 x the upper limit of normal (ULN) as defined by the central laboratory, or
• alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) >2.5 x ULN as defined by the central laboratory, or
• aspartate aminotransferase (AST)/(serum glutamic oxaloacetic transaminase (SGOT) >2.5 x ULN as defined by the central laboratory.
[21] Hematologic: 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 measurement of HbA1c.
[22] Malignancy: have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator.
[23] Allergy: have known hypersensitivity or allergy to any of the study insulins or their excipients.
[24] Glucocorticoid therapy: are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy or have received such therapy within the 8 weeks immediately preceding Visit 1.
[25] Triglycerides: have fasting triglycerides >400 mg/dL (>4.5 mmol/L) at Visit 1 as determined by the central laboratory.
[26] Sleep cycle: have irregular sleep/wake cycle in the investigator’s opinion.
[27] Adherence to protocol: have any other conditions (including known drug or alcohol abuse or psychiatric disorder) that preclude the patient from following and completing the protocol.
[28] Lilly or Boehringer Ingelheim employees: are Lilly employees or representatives or Boehringer Ingelheim employees.
[29] Site personnel: 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.
[30] Non-approved drug: have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry.
[31] Prior study participation: are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or nonapproved use of a drug or device other than LY2605541, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
[32] Prior study with LY2605541: have previously completed or withdrawn from this study after having signed informed consent or any other study investigating LY2605541 after receiving at least 1 dose of investigational product.
[33] General restrictions: are unable and/or unwilling to provide informed consent, make themselves available for the duration of the study, or abide by study procedures and restrictions.
[39] Lipid-lowering medications:
• are using niacin preparations as a lipid-lowering medication and bile acid sequestrants within 90 days prior to Visit 1; or,
• are using lipid-lowering medication at a dose that has not been stable for ≥90 days prior to Visit 1.
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E.5 End points |
E.5.1 | Primary end point(s) |
A change of HbA1c from baseline to 52 weeks that is not inferior to glargine. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Nocturnal and total hypoglycemia rates and incidences superior to glargine, proportion of patients with HbA1c <7% at 52 weeks of treatment (also HbA1c <7% with no nocturnal hypoglycemia, FPG by laboratory, FBG by SMBG, weight change from baseline, SMBG 6-pt profile, HbA1c, insulin dose, number of dose adjustments to steady state, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, insulin and insulin analog antibodies, other safety endpoints such as serious adverse events, vitals, treatment-emergent adverse events, Health Outcomes measurements EQ-5D, ITSQ, and LBSS. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All gates objective endpoints are at 52 weeks of treatment for many of the non-gated secondary endpoints have various timepoints such as 0 to 12 weeks, 0 to 26 weeks, 0 to 52 weeks, 0 to 78 weeks, 12 to 26 weeks, 26 to 52 weeks, 52 to 78 weeks for nocturnal and total hypoglycemia incidences; 0 to 12 weeks, 0 to 52 weeks, 0 to 78 weeks, 12 to 26 weeks, 26 to 52 weeks, 52 to 78 weeks for nocturnal and total hypoglycemia rates; 52 and 78 weeks for FPG by laboratory, 52 and 78 weeks for proportion of patients with HbA1c <7%, and the same as immediately above with no nocturnal hypoglycemia, and HbA1c change from baseline |
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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 | 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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Czech Republic |
Finland |
Germany |
Greece |
Hungary |
Israel |
Italy |
Lithuania |
Mexico |
New Zealand |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Spain |
Turkey |
United Kingdom |
United States |
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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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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 10 |