Efficacy of once weekly exenatide long acting release and once daily insulin glargine in patients with Type 2 diabetes treated with metformin alone or in combination with sulphonylurea. - GWBR

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2007-002957-22-DE
• Date of registration: 28/10/2008
• Prospective Registration: No
• Primary sponsor: Eli Lilly and Company
• Public title: Efficacy of once weekly exenatide long acting release and once daily insulin glargine in patients with Type 2 diabetes treated with metformin alone or in combination with sulphonylurea. - GWBR
• Scientific title: Efficacy of once weekly exenatide long acting release and once daily insulin glargine in patients with Type 2 diabetes treated with metformin alone or in combination with sulphonylurea. - GWBR
• Date of first enrolment: 30/05/2008
• Target sample size: 456
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002957-22
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Denmark, France, Germany, Greece, Hungary, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Present with type 2 diabetes based on the disease diagnostic criteria as described by the World Health Organization (WHO) (refer to Section 4.1.1).
[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 25 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] Have been treated with Met for at least 3 months and have been taking a stable dose of >=1500 mg/day immediate-release Met or extended-release Met alone for at least 8 weeks prior to screening, unless lower doses are required due to tolerability concerns.
OR
Have been treated with Met for at least 3 months and have been taking a stable dose of >=1500 mg/day immediate-release Met or extended-release Met alone for at least 8 weeks prior to screening, unless lower doses are required due to tolerability concerns and have been treated with SU for at least 3 months and have been taking a stable dose of at least an optimally effective dose of brand of SU for 8 weeks prior to screening (refer to protocol table GWBR.1).
If combined Met plus SU OAD preparations (such as Glucovance) are used, the total daily dose of each component needs to meet the criteria as outlined above.
[7] This inclusion criterion applies to females of child-bearing 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 (e.g., use of oral contraceptives or approved hormonal implant; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for at least 6 weeks prior to screening.
? Agree to continue to use a reliable method of birth control (see above) 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:
[8] Are Lilly, Amylin, or Alkermes employees.
[9] 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.
[10] 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] Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, alanine aminotransaminase (ALT), or serum glutamic pyruvic transaminase (SGPT) greater than three times the upper limit of the reference range.
[12] Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.2 mg/dL for females.
[13] Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
[14] Have known hemoglobinopathy or chronic anemia (hemoglobin concentration <11.5 gm/dL [115 gm/L] for males, <10.5 gm/dL [105 gm/L] for females).
[15]Have had greater than three episodes of major hypoglycemia within 6 months prior to screening. Refer to Section 5.5.4 for more information on hypoglycemia.
[16] Have any contraindication for the OAD which they use.
[17] Have a known allergy or hypersensitivity to insulin glargine, exenatide LAR, or excipients contained in these agents.
[18] Are known to have active proliferative retinopathy.
[19] Have been treated within 4 weeks of screening with systemic glucocorticoid therapy by oral, intravenous (IV), or intramuscular (IM) route, or are regularly treated with potent, inhaled intranasal steroids that are known to have a high rate of systemic absorption. Exceptions to this criterion include patients who are receiving glucocorticoid therapy for corticotropic hypopituitary deficiency (e.g., Addison disease).
[20] 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.
[21] Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening:
? Insulin
o Thiazolidinediones (e.g., Actos [pioglitazone] or Avandia [rosiglitazone])
? Alpha-glucosidase inhibitors (e.g., Glyset [miglitol] or Precose [acarbose])
? Meglitinides (e.g., Prandin [repaglinide] or Starlix [nateglinide]).
? Byetta (exenatide BID formulation)
? Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia [sitagliptin], Galvus[vildagliptin])
? Symlin (pramlintide acetate).
[22] Have had an organ transplant.
[23] Have donated blood within 30 days of screening.
[24] Have previously completed or withdrawn from this study or any other study investigating exenatide LAR.
[25] 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.
[26] Are c

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-

Trade Name: Lantus
Product Name: insulin glargine
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: to estimate difference in change in HbA1c from baseline to treatment endpoint (26 weeks) between 2.0 mg exenatide LAR once weekly and insulin glargine QD in patients with type 2 diabetes and inadequate glycemic control using Met alone or in combination with SU. Superiority of exenatide LAR with respect to change in HbA1c will be concluded if the upper limit of the 95% confidence interval for treatment difference is less than zero. Non-inferiority will be concluded if upper limit of the confidence interval is >=0.0% and <0.3%. Hypotheses will be tested hierarchically.

Secondary Objective: to compare exenatide LAR and insulin glargine with respect to:
• the proportion of patients achieving HbA1c <=7% and <=6.5%.
• fasting serum glucose
• change in body weight
• 1,5-anhydroglucitol (1,5-AG)
• 8-point self-monitored blood glucose (SMBG) profile (blood glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, at bedtime, and at the 0300 hour)
• serum lipids (total cholesterol [TC], high-density lipoprotein cholesterol [HDL C], fasting triglycerides, calculated low-density lipoprotein cholesterol [LDL C])
• frequency and rate of hypoglycemic events (overall, daytime, and nocturnal) in the set of patients using Met alone or in combination with SU
• safety and tolerability
• patient-reported health outcomes
• long-term maintenance of glycemic control, safety, and tolerability.

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

Secondary ID(s)

H80-MC-GWBR(b)

2007-002957-22-NL

N/A

Ethics review

Status: Approved
Approval date: 25/03/2008
Contact:

Results

• Results available: Yes
• Date Posted: 04/01/2019
• Date Completed: 30/01/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-002957-22/results