A Randomized Trial Comparing Exenatide with Placebo in Subjects with Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications - GWCO

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-003843-36-GR
• Date of registration: 18/02/2009
• Prospective Registration: No
• Primary sponsor: Eli Lilly and Company
• Public title: A Randomized Trial Comparing Exenatide with Placebo in Subjects with Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications - GWCO
• Scientific title: A Randomized Trial Comparing Exenatide with Placebo in Subjects with Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications - GWCO
• Date of first enrolment: 13/01/2009
• Target sample size: 260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003843-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Greece

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Have T2DM
[2] Are at least 18 years of age
[3] Have been taking basal insulin glargine at a dose of =20 units/day for at least 3 months prior to Visit 1
[4] Have been receiving glargine alone or in combination with one of the following OAM regimens for the 3 months prior to Visit 1:metformin,pioglitazone, a combination of metformin and a pioglitazone at a stable dose for 6 weeks prior to Visit 1 and do not meet exclusion criteria 11.
[5] Have an A1C =7.1% and =10.5%.
[6] Have a body mass index (BMI) =45 kg/m2.
[7] Show no evidence of cardiovascular disease as determined by a normal electrocardiogram (ECG)
[8] Have a history of stable body weight
[9] Liver enzyme tests (ALT, AST) are not greater than 1.5 times the upper limit of the reference range
[10] Are female subjects with serum creatinine level =1.4 mg/dL or male
subjects with serum creatinine level =1.5 mg/dL.
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:
[11] Are currently taking a dose or combination of OAM that is not allowed with concurrent use of insulin glargine per local product label
[12] Have taken any glucose-lowering medications not included in
Inclusion Criteria [3] and [4] in the 3 months prior to Visit 1 for more than 1 week or within 1 month of screening.
[13] Have taken any insulin other than glargine within the 3 months prior to Visit 1 for more than 1 week or within 1 month of screening
[14] Have had more than one episode of major hypoglycemia, within 6 months prior to Visit 1
[15] 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.
[16] Women who are breastfeeding.
[17] presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic,
gastrointestinal disease, or any other serious disease
[18] Have a history of renal transplantation or receiving dialysis
[19] Are subjects with a malignancy (see protocol for specifics)
[20] Have contraindication or known hypersensitivity or allergy to exenatide or to any of the product components
[21] Have used a drug for weight loss within 3 months prior to Visit 1 for more than 1
week or within 1 month of screening
[22] Are currently on a supervised weight-loss program
[23] 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 condition known to interfere with the A1C methodology.
[24] Are receiving chronic systemic glucocorticoid therapy or have received such therapy within the 8 weeks immediately preceding Visit 1.
[25] Have an irregular sleep/wake cycle
[26] Have any other condition that renders the subject unable to understand the
nature, scope, and possible consequences of the study,
[27] Have received treatment within 30 days before Visit 1 with a drug that has not received regulatory approval for any indication at the time of study entry.
[28] Are investigator site personnel directly affiliated with this study and/or their immediate families.
[29] Are employed by Lilly or Amylin Pharmaceuticals, Inc.
[30] Have previously completed or withdrawn from this study after signing
the ICD.
[31] If on metformin and have contraindication to metformin use
[32] If on metformin, have had a radiologic contrast study performed within 48 hours prior to Visit 1.
[33] If on pioglitazone, have a contraindication to pioglitazone including NYHA Class II-IV CHF or are on a dose of pioglitazone that is contraindicated with insulin in that country.


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 10045242 Term: Type II diabetes mellitus

Intervention(s)

Trade Name: Byetta
Product Name: Exenatide
Product Code: LY2148568
Pharmaceutical Form: Solution for injection
INN or Proposed INN: exenatide
CAS Number: 141732-76-5
Current Sponsor code: LY2148568
Other descriptive name: exendin-4, exendin 4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: to compare the efficacy and safety of exenatide to placebo when added to basal insulin glargine with or without OAMs with respect to:
• percentage of subjects with A1C =7.0% and A1C =6.5% at 30 weeks;
• change from baseline in fasting glucose;
• 7-point self-monitored blood glucose (SMBG) profiles and mean blood glucose (BG) measurement based on 7-point SMBG;
• change from baseline in fasting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides;
• change from baseline in body weight (kg);
• change from baseline in waist circumference (cm);
• change from baseline in insulin dose (24-hour total international units [IU]
and total units/kg body weight);
• change from baseline in seated systolic (SBP) and diastolic blood pressure (DBP);
• safety, as measured by:
o self-reported hypoglycemic episodes;
o treatment-emergent adverse events (TEAEs);

Main Objective: to test the hypothesis that twice daily exenatide plus titration of basal insulin is superior to placebo plus titration of basal insulin on glycemic control as measured by change in A1C from baseline (Visit 3) to Week 30, with or without oral antihyperglycemic medications (OAMs) in adult subjects with T2DM who are suboptimally controlled (A1C =7.1% and =10.5%).

Primary end point(s): The primary analysis variable is the change in A1C, and the primary analysis set is FAS. The conclusion for the primary analysis will be based on the pvalue for the test of treatment effect at 30 weeks.

Secondary ID(s)

H8O-US-GWCO