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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
|
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 compare the change in HbA1c from baseline (randomization) after 24 weeks of treatment with one of two basal bolus titration algorithms, in adult patients with type 2 diabetes mellitus who have not achieved adequate glycemic control on basal insulin (glargine, NPH, or detemir) with oral antihyperglycemic medications. |
|
E.2.2 | Secondary objectives of the trial |
Frequency and rate of self-reported hypoglycemic episodes per 30 days and per year (total, nocturnal, and severe) (overall and in subjects ≥65 years of age) change in body weight proportions of subjects achieving HbA1c target values (HbA1c ≤7.0% and ≤6.5%) at end of study (overall and in subjects ≥65 years of age) time to reach HbA1c target values (HbA1c ≤7.0% and ≤6.5%) HbA1c change from baseline (randomization) within each treatment algorithm change in fasting glucose (overall and in subjects ≥65 years of age) change in 1,5-AG 7-point SMBG profile data including average blood glucose values for each timepoint measurement insulin dose: total, basal (glargine), and prandial (lispro) (24-hour total measured in U/d and U/kg) at end of study. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Have type 2 diabetes (per World Health Organization [WHO] Classification of Diabetes). [2] Are ≥18 and ≤85 years of age at the time of Visit 1. [3] Have been treated for at least 90 days with insulin (glargine, NPH, or detemir) in combination with oral antihyperglycemic agents as monotherapy, dual, or triple therapy (sulfonylurea, meglitinide, metformin, pioglitazone, or dipeptidyl peptidase-4 [DPP-4] inhibitor) and, in the opinion of the investigator, requires further intensification of therapy. [4] Are treated with insulin (glargine, NPH, or detemir) at least 20 U/day at study entry. [5] Have an HbA1c value >7.0% and ≤12.0% according to the central laboratory at Visit 1. Note: for patients who enter the study on NPH insulin or detemir, or on glargine with HbA1c >7.0% and fasting blood glucose >120 mg/dL, a 6-week lead-in period will be required for glargine optimization. For a patient on glargine with HbA1c >7.0% and fasting blood glucose ≤120 mg/dL, no leadin period is required and he or she may be randomized at Visit 2. [6] Capable of, and willing, to do the following: inject insulin with a prefilled pen and perform self blood glucose monitoring and record keeping as required by this protocol, as determined by the investigator. [7] Have given written informed consent to participate in this study in accordance with local regulations. |
|
E.4 | Principal exclusion criteria |
[8] Prior rapid- or short-acting insulin therapy: patients receiving scheduled long-term short-acting or rapid-acting or premixed insulin therapy within the past 6 months will not be eligible to participate in the study. Patients who have previously received short- or rapid-acting insulin as part of short-term insulin therapy (during gestational diabetes, or during an acute hospitalization or illness) or occasional use will be allowed to participate in this study. Occasional use (e.g., 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. [9] Concomitant medications: glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., exenatide or liraglutide), alpha-glucosidase inhibitor (e.g., acarbose, miglitol, or voglibose) or rosiglitazone use concurrently or within 3 months prior to entry into study. [10] Severe hypoglycemia: have had more than one episode of severe hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the study. [11] Excessive insulin resistance: received a total daily dose of insulin >2.0 U/kg at the time of randomization. [12] Morbid obesity: defined as a body mass index ≥45 kg/m2. [13] Malignancy: have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years [14] Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association [NYHA] Cardiac Disease Classification) or have congestive heart failure (CHF) requiring pharmacologic treatment or, in the investigator’s opinion, have severe dependent edema (i.e., edema of the feet or ankles) or have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis. [15] Renal: have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine ≥2 mg/dL if not on metformin. [16] Hepatic: have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) >3x the upper limit of the reference range as defined by the central laboratory. [17] Hematologic: have known hemoglobinopathy or chronic anemia or other known blood disorder. [18] Reproductive: (for women) are pregnant or intend to become pregnant during the course of the study; are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable; or are breastfeeding. [19] Allergy: have known allergy to insulin lispro, insulin glargine, or excipients contained in these products. [20] Glucocorticoid therapy: receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately before Visit 1. [21] Adherence to protocol: have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the patient from following and completing the protocol. [22] Prior participation: are currently enrolled in, or have participated in, an interventional medical, surgical, or pharmaceutical drug or device or off-label use study (an investigational study in which a medical or surgical treatment was given) within 30 days prior to entry into the study, or persons who have previously completed or withdrawn from this study (after having signed the informed consent document). Patients may be ineligible if they are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [23] 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. [24] Site personnel: investigators or site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [25] are employed by Eli Lilly and Company [26] Screen failure: have previously been screen-failed from this study for any reason. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to compare the change in glycated hemoglobin (HbA1c) from baseline (randomization) after 24 weeks of treatment with one of two basal-bolus algorithms in adult patients with type 2 diabetes mellitus not achieving adequate glycemic control on basal insulin (glargine, NPH, or detemir) with oral antihyperglycemic medications. |
|
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
2 escalation algorhythms are compared |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 last subject |
|
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |