The COMPLETE T1D Trial: COMParison of Insulin Lispro Protamine Suspension and DETEmir in Type 1 Diabetes Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Insulin Detemir) in Basal-Bolus Therapy for Patients with Type 1 Diabetes - COMPLETE T1D Trial

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-006375-21-HU
• Date of registration: 16/02/2007
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Ltd.
• Public title: The COMPLETE T1D Trial: COMParison of Insulin Lispro Protamine Suspension and DETEmir in Type 1 Diabetes Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Insulin Detemir) in Basal-Bolus Therapy for Patients with Type 1 Diabetes - COMPLETE T1D Trial
• Scientific title: The COMPLETE T1D Trial: COMParison of Insulin Lispro Protamine Suspension and DETEmir in Type 1 Diabetes Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Insulin Detemir) in Basal-Bolus Therapy for Patients with Type 1 Diabetes - COMPLETE T1D Trial
• Date of first enrolment: 12/04/2007
• Target sample size: 335
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006375-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: 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

Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Have type 1 diabetes based on the disease diagnostic criteria (World Health Organization [WHO] Classification, see Protocol Attachment IOOZ.2).
[2] Aged >=18 years.
[3] Duration of diabetes >=1 year.
[4] Have a hemoglobin A1c (HbA1c) 1.2 to 2.0 times the upper limit of the normal (ULN) reference range within 30 days prior to Visit 1 or collected and analyzed at a local laboratory at Visit 1.
[5] Body mass index (BMI) <=35 kg/m2.
[6] As determined by the investigator, are capable and willing to do the following:
• perform self monitoring of blood glucose (SMBG),
• complete patient diaries as required for this protocol,
• use the insulin injection device(s) according to the instructions provided,
• are receptive to diabetes education,
• comply with the required study 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:
9] Are taking any oral antihyperglycemic medications (OAMs).
[10] Have had more than one episode of severe hypoglycemia, as defined in the Abbreviations and Definitions section of the protocol, within 6 months prior to entry into the study.
[11] 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.
[12] Women who are breastfeeding.
[13] Have one of the following concomitant diseases: presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease.
[14] Have a history of renal transplantation or are currently receiving renal dialysis or creatinine greater than 2.0 mg/dL (177 µmol/L).
[15] 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 the reference range, as defined by the local laboratory) or have albumin value above or below the normal reference range, as defined by the local laboratory.
[16] Are undergoing therapy for a malignancy other than basal cell or squamous cell skin cancer.
[17] Have known hypersensitivity or allergy to any of the study insulins or excipients of the study insulins.
[18] 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.
[19] Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding Visit 1.
[20] Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).
[21] Have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes the patient from following and completing the protocol.
[22] 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.
[23] 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.
[24] Are Lilly employees.
[25] Have previously completed or withdrawn from this study after having signed the informed consent document.


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

Health Condition(s) or Problem(s) studied

type 1 diabetes
MedDRA version: 8.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus

Intervention(s)

Trade Name: Humalog NPL 100 U/ml suspension for injection in cartridge
Product Name: Humalog NPL
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: LY275585[P]
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Humalog NPL 100 U/ml Pen, suspension for injection
Product Name: Humalog NPL
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: LY275585[P]
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Humalog 100 U/ml, solution for injection in cartridge
Product Name: Humalog
Pharmaceutical Form: Solution for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: LY275585[P]
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Humalog Pen 100 U/ml, solution for injection
Product Name: Humalog
Pharmaceutical Form: Solution for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: LY275585[P]
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Humalog 100 U/ml, solution for injection in vial
Product Name: Humalog
Pharmaceutical Form: Solution for injection
INN or Proposed INN: insulin lispro
CAS Number: 133107-64-9
Current Sponsor code: LY275585[P]
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Levemir 100 U/ml solution for injection in a cartridge
Product Name: levemir
Pharmaceutical Form: Solution for injection
INN or Proposed INN: insulin detemir
CAS Number: 270588-25-5
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 basal analog insulin lispro protamine suspension injected two times a day is noninferior to basal analog insulin detemir injected two times a day, as measured by change in hemoglobin A1c (HbA1c) from baseline (Visit 2) to 32 weeks in adult patients with type 1 diabetes when used in combination with bolus insulin lispro injected three times a day. The noninferiority margin is 0.4%.

Secondary Objective: •NPL is noninferior to detemir within a basal-bolus regimen as measured by standard deviation of fasting blood glucose as a measure of intrapatient glycemic variability
•NPL is noninferior to insulin detemir within a basal-bolus regimen as measured by change in absolute body weight
Additional secondary objectives are to compare efficacy and safety with respect to
•actual and change from baseline HbA1c value at 8, 16, and 24 weeks and at endpoint
•percentage of patients with HbA1c =7.0% and HbA1c =6.5% at endpoint
•7-point self-monitored blood glucose profiles and glycemic variability from these profiles at endpoint
•safety, as measured by
+ the incidence, rate of hypoglycemic episodes and severe hypoglycemia
+ absolute body weight and incremental weight change from baseline to endpoint
+ treatment-emergent adverse events
•insulin dose at endpoint

Primary end point(s): The primary objective of this study is to test the hypothesis that basal analog insulin lispro protamine suspension injected two times a day is noninferior to basal analog insulin detemir injected two times a day, as measured by change in hemoglobin A1c (HbA1c) from baseline (Visit 2) to 32 weeks in adult patients with type 1 diabetes when used in combination with bolus insulin lispro injected three times a day. The noninferiority margin is 0.4%.

Discontinuation of Patients
The criteria for enrollment must be followed explicitly. If a patient who does not meet enrollment criteria is inadvertently enrolled, that patient should be discontinued from the study drug, but can be allowed to continue in the study in order to provide the follow-up data needed for the analysis of the entire intention-to-treat population.
Patients will be discontinued from the study drug and/or from the study in the following circumstances:
• If any of Exclusion Criteria [9] or [11] through [25] is observed or develops after entry or enrollment. In this case, the patient will be discontinued from the study at the next visit, or sooner if patient safety is the rationale for the exclusion criterion.
• If the patient is off study medication for more than 7 consecutive days.
• If the investigator decides that the patient should be withdrawn. If this decision is made because of a serious adverse event or a clinically significant laboratory value, the study drug is to be discontinued and appropriate measures are to be taken. Lilly or its designee is to be alerted immediately.
• If the patient or attending physician requests that the patient be withdrawn from the study.
• If the investigator or Lilly, for any reason, stops the study or stops the patient’s participation in the study.
• If the investigator determines that the patient is noncompliant and should be discontinued.
Patients who discontinue study drug early should have early discontinuation procedures performed as shown in the Study Schedule (Protocol Attachment IOOZ.1).

Secondary ID(s)

F3Z-MC-IOOZ(a)