Safety and Efficacy of Exenatide Once Weekly Injection versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients with Type 2 Diabetes - GWCH

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000854-11-SK
• Date of registration: 09/09/2008
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: Safety and Efficacy of Exenatide Once Weekly Injection versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients with Type 2 Diabetes - GWCH
• Scientific title: Safety and Efficacy of Exenatide Once Weekly Injection versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients with Type 2 Diabetes - GWCH
• Date of first enrolment: 07/11/2008
• Target sample size: 822
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000854-11
• 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: yes Placebo: no Other: no

Countries of recruitment

Belgium, France, Germany, Hungary, Italy, Poland, Slovakia, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients, males or females, are eligible to be included in the study only if they meet all of the following criteria:
[1] Present with type 2 diabetes based on the disease diagnostic criteria as described by the World Health Organization (WHO) and are treated with diet and exercise alone.
[2] Are at least 18 years of age at screening
[3] Have suboptimal glycemic control as evidenced by an HbA1c between 7.1% and 11.0%, inclusive
[4] Have a body mass index (BMI) of 23 kg/m2 to 45 kg/m2, inclusive
[5] Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).
[6] This inclusion criterion applies to females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only.
? Are not breastfeeding.
? Test negative for pregnancy at the time of screening based on a blood serum pregnancy test.
? Intend not to become pregnant during the study.
? Have practiced a reliable method of birth control 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.

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:
Patients will be excluded from the study if they meet any of the following criteria:
[7] Are Lilly, Amylin, or Alkermes employees.
[8] 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.
[9] Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study, including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure (New York Heart Association Class III or IV [CCNYHA 1994]), coronary artery bypass surgery, or angioplasty; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
[11] regarding local label exclusions for cardiac failure.
[10] Have any contraindication for the study drug (exenatide, metformin, sitagliptin, or pioglitazone, or the excipients contained in these agents) to which they may be assigned.
[11] Have had poorly controlled blood pressure within the last 4 weeks.
[12] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, alanine aminotransferase (ALT), or serum glutamic pyruvic transaminase (SGPT) greater than 2.5 times the upper limit of the reference range.
[13] Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine > or=1.5 mg/dL for males and > or=1.2 mg/dL for females.
[14] Have active or untreated malignancy, or have been in remission from clinically significant malignancy for less than 5 years.
[15] Have known hemoglobinopathy or chronic anemia (hemoglobin concentration <115 g/L for males, <105 g/L for females).
[16] Have had more than 2 episodes of major hypoglycemia within 6 months prior to screening.
[17] Patients with a history of severe GI disorder (e.g., gastroparesis)
[18] Patients with a history of acute or chronic pancreatitis.
[19] Are known to have active proliferative retinopathy.
[20] Have been treated within 8 weeks of screening with systemic glucocorticoid therapy by oral, intravenous, or intramuscular route, or are regularly treated with potent, inhaled or intranasal steroids that are known to have a high rate of systemic absorption. Exceptions to this criterion include patients who are receiving chronic glucocorticoid therapy for corticotropic hypopituitary deficiency (e.g., Addison disease).
[21] Have been treated with drugs that promote weight loss (e.g., Xenical® [orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of screening.
[22] Have been treated with any antidiabetic agent within 3 months prior to screening.
[23] Have had an organ transplant.
[24] Have any exclusion criteria required by local law.
[25] Have previously completed or discontinued study drug in this study, withdrawn from this study or any other study investigating exenatide once weekly.
[26] 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.
[27] Are currently enrolled in any other clinical study.
[28] Have any other condition that renders them unable to understand the nature, scope, and possible consequences of the study or precludes them from following and completing the protocol, in the o

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

Health Condition(s) or Problem(s) studied

Type 2 Diabetes
MedDRA version: 9.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus

Intervention(s)

Product Name: Exenatide
Product Code: LY2148568, AC2993
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: Exenatide
CAS Number: 141732-76-5
Current Sponsor code: AC2993, LY2148568
Other descriptive name: exendin-4,exendin 4, exenatide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.0-
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Actos
Product Name: Thiazolidinedione (TZD)
Pharmaceutical Form: Capsule*
INN or Proposed INN: pioglitazone
CAS Number: 111025-46-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
INN or Proposed INN: pioglitazone
CAS Number: 111025-46-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Januvia
Product Name: DPP-4
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sitagliptin
CAS Number: 790712-60-6
Other descriptive name: DPP-4 inhibitor
Concentration unit: mg milligram(s)
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: metformin
Pharmaceutical Form: Tablet
INN or Proposed INN: metformin
CAS Number: 657-24-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change in HbA1c from baseline to week 26.

Main Objective: To test the hypothesis that exenatide once weekly is superior to metformin, sitagliptin, and pioglitazone in HbA1c reduction at 26 weeks compared to baseline, in drug-naive patients with type 2 diabetes who are inadequately treated with diet and exercise.

Secondary Objective: To compare exenatide once weekly to metformin, sitagliptin, and pioglitazone over 26 weeks with respect to:
• the proportion of patients achieving HbA1c • change in fasting serum glucose
• change in body weight
• 7-point self-monitored blood glucose (SMBG) profile
• change in serum lipids
• incidence of hypoglycemic events
• change in systolic and diastolic blood pressure
• safety and tolerability
• health outcomes

Secondary ID(s)

N/A

2008-000854-11-HU

H80-MC-GWCH