Comparison of Premixed Insulin Lispro Low Mixture and Mid Mixture Regimens with Separate Basal and Bolus Insulin Injections in Patients with Type 2 Diabetes with Inadequate Glycemic Control on Oral Therapy who Consume Light Breakfast

• Register: EUCTR
• Last refreshed on: 8 May 2012
• Main ID: EUCTR2007-005061-36-PT
• Date of registration: 11/03/2008
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Ltd.
• Public title: Comparison of Premixed Insulin Lispro Low Mixture and Mid Mixture Regimens with Separate Basal and Bolus Insulin Injections in Patients with Type 2 Diabetes with Inadequate Glycemic Control on Oral Therapy who Consume Light Breakfast
• Scientific title: Comparison of Premixed Insulin Lispro Low Mixture and Mid Mixture Regimens with Separate Basal and Bolus Insulin Injections in Patients with Type 2 Diabetes with Inadequate Glycemic Control on Oral Therapy who Consume Light Breakfast
• Date of first enrolment: 06/06/2008
• Target sample size: 325
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005061-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Portugal, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Present with type 2 diabetes mellitus, based on a history and clinical impression that is consistent with the World Health Organization [WHO] Classification of Diabetes (see Protocol Attachment S020.3).
[2] Patients are =30 years of age and <75 years of age.
[3] Have been receiving oral antihyperglycemic medications (OAMs) including metformin, without insulin for at least 90 days immediately prior to the study (Visit 1). The OAMs should include at least two of the following (one of which must be metformin) at maximally tolerated doses, AND meet the additional dosing criteria shown:

Metformin, Minimum Dose: 1500 mg/day

Sulfonylurea (SU) Minimum Dose: half the maximum daily dose, according to the licence in the participating country.

Thiazolidinedione (TZD) Minimum Dose: 30 mg/day pioglitazone, OR
4 mg/day rosiglitazone

NOTE: The OAMs also must be used in accordance with the product label and be approved for use with insulin in the patient’s country (see Exclusion Criterion [8]).
NOTE: Combination treatments of the OAMs above are acceptable if they meet the criteria above. For example, Avandamet® (rosiglitazone maleate and metformin hydrochloride) would cover the categories of a TZD and metformin.
[4] Have a hemoglobin A1c (HbA1c) =7.0% and <11.0% as measured at Visit 1.
[5] Routinely consume less than 15% of their daily caloric intake at breakfast (defined as a meal consumed between 5 am and 10 am) as determined based on the history and a 1-day dietary recall.
[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) to adjust insulin doses, and to provide 7-point SMBG profiles before principal study visits;
• use the patient diary as required for this protocol;
• be receptive to diabetes education (as per routine practice), including following dietary and lifestyle advice as appropriate;
• comply with the required study visits and be willing to receive regular telephone calls between visits.
[7] Have given written informed consent to participate in this study in accordance with local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[8] Are taking a TZD dose greater than what is indicated in combination with insulin according to the TZD label in their respective country.
NOTE: In countries where the combination of a TZD and insulin is contraindicated, patients taking a TZD must have been on a prestudy regimen of three OAMs in Inclusion Criteria [3], and must discontinue the TZD at Visit 1.
[9] Are taking any other glucose-lowering agents (such as meglitinide, alpha-glucosidase inhibitors, DPP-lV inhibitors, etc.) not mentioned in Inclusion Criterion [3].
[10] Have taken acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide in the past 6 weeks, or for a total of 30 days or more, in the last 24 weeks.
[11] Have a body mass index greater than 40 kg/m2.
[12] Have had more than one episode of severe hypoglycemia (within 24 weeks prior to entry into the study (Visit 1).
[13] 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.
[14] Are women who are breastfeeding.
[15] Have cardiac disease with a functional status that is Class III or IV (see Protocol Attachment S020.4); or, if taking a TZD, have cardiac disease of a less severe functional status, which would contraindicate in their respective country the use of TZD alone or in combination with insulin.
[16] Have a history of renal transplantation, or are currently receiving renal dialysis.
[17] Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (alanine transaminase [ALT] OR aspartate transaminase [AST] greater than 2.5 times the upper limit of the reference range).
[18] Are undergoing therapy for a malignancy, other than basal-cell or squamous-cell skin cancer.
[19] Have known hypersensitivity or allergy to any of the study insulins or excipients of the study insulins.
[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.
[21] Have received systemic glucocorticoid therapy within the 3 months prior to Visit 1.
NOTE: Topical preparations, nasal preparations, intra-articular administration, as well as physiologic replacement for Addison’s disease and hypopituitarism are permitted.
[22] Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).
[23] Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the patient from following and completing the protocol.
[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 a serum creatinine concentration that contraindicates use of metformin according to the country-specific metformin product label.
[28] Have known metabolic or lactic acidosis.
[29] Have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
[30] Have had a radiologic contrast study within 48 hours prior to entry in the study (Visit 1) or plan to have such a procedure or surgery performed during the study.
[31]

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

type 2 diabetes mellitus
MedDRA version: 9.1 Level: LLT Classification code 10063624 Term: Type II diabetes mellitus inadequate control

Intervention(s)

Trade Name: Humalog Mix25
Product Name: Humalog Mix25
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: insulin lispro low mixture
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Humalog Mix50
Product Name: Humalog Mix50
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: insulin lispro mid mixture
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Humalog
Product Name: Humalog
Pharmaceutical Form: Solution for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Lantus
Product Name: Insulin glargin
Pharmaceutical Form: Solution for injection
INN or Proposed INN: insulin glargine
CAS Number: 160337-95-1
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: The primary objective of this study is to test the hypothesis that glycemic control achieved when initiating insulin treatment with insulin lispro mid mix /low mix as a single daily injection either before midday or evening meal, and progressing up to three daily injections of mid mix/low mix is noninferior to that achieved when initiating insulin glargine as a single daily injection and progressing to up to three additional daily injections of meal-time insulin lispro.
Glycemic control will be determined by measuring the mean change from baseline to endpoint of hemoglobin A1c (HbA1c) after approximately 48 weeks, in patients with type 2 diabetes mellitus who have a habit of consuming less than 15% of their daily caloric intake at morning meal and who have inadequate glycemic control (HbA1c =7%) on oral antihyperglycemic medication(s). A noninferiority margin of 0.4% for HbA1c will be used.

Secondary Objective: To report the % of patients at endpoint using each of possible final insulin regimens. Additional secondary objectives are to compare effects of the 2 treatment regimens, with respect to
•mean HbA1c-change (16, 32, 48 weeks)
•percentages of patients achieving HbA1c =6.5%and<7% (16, 32, 48 weeks)
•7-point self-monitored blood glucose (SMBG) profiles at baseline, 16, 32, 48 weeks
•mean change from baseline in postprandial blood glucose, 16, 32, 48 weeks
•mean change from baseline to endpoint in lipid + cholesterol profiles
•mean daily total, basal and prandial insulin dose at 16, 32, 48 weeks
•body weight change from baseline to endpoint
•change of dietary pattern
•safety, as measured by the incidence and rate of self-reported hypoglycemic episodes, including all, severe, daytime and nocturnal hypoglycemia
•incidence of treatment-emergent adverse events

Primary end point(s):

Secondary ID(s)

F3Z-EW-S020

2007-005061-36-ES