Comparison of the Effect of Exenatide Versus Sitagliptin on 24-hour Average Glucose in Patients With Type 2 Diabetes on Metformin or a Thiazolidinedione

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00729326
First received: August 4, 2008
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

This study is designed to compare the short-term effects and mechanisms of action of exenatide with those of sitagliptin when either is added to an oral agent(metformin or a thiazolidinedione [TZD]) in adult patients with type 2 diabetes mellitus(T2DM) with inadequate glycemic control.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: exenatide
Drug: sitagliptin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Comparison of the Effect of Exenatide vs. Sitagliptin on 24-hour Average Glucose in Patients With Type 2 Diabetes on Metformin or a Thiazolidinedione

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Change in Time-averaged Glucose During a 24 Hour Period [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in time-averaged glucose during a 24-hour period from baseline to endpoint (i.e., time-averaged glucose over 24 hours at endpoint minus time-averaged glucose over 24 hours at baseline).


Secondary Outcome Measures:
  • Change in Two-hour Postprandial Glucose After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in 2 hour post-prandial glucose after the morning meal from baseline to endpoint (i.e., glucose level 2 hours after the morning meal at baseline minus glucose level 2 hours after the morning meal at endpoint)

  • Change in Fasting Blood Glucose After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in fasting blood glucose after the morning meal from baseline to endpoint (i.e., fasting blood glucose after the morning meal at baseline minus fasting blood glucose after the morning meal at endpoint)

  • Change in Postprandial Glucagon Area Under the Concentration-time Curve (AUC) After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in Postprandial Glucagon AUC after the morning meal (t=0 to 4 hours) (i.e., Glucagon AUC over the first 4 hours following the morning meal at baseline minus glucagon AUC over the first 4 hours following the morning meal at endpoint)

  • Change in Postprandial Glucagon AUC Excursion After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in postprandial glucagon AUC excursion after the morning meal (t=0 to 4 hours) (i.e., glucagon AUC excursion for 4 hours following the morning meal at baseline minus glucagon AUC excursion for 4 hours following the morning meal at endpoint)

  • Change in Postprandial Triglyceride AUC After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in postprandial triglyceride AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial triglyceride AUC after the morning meal at baseline minus postprandial triglyceride AUC after the morning meal at endpoint)

  • Change in Postprandial Triglyceride AUC Excursion After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in postprandial triglyceride AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial triglyceride AUC excursion after the morning meal at baseline minus postprandial triglyceride AUC excursion after the morning meal at endpoint)

  • Change in Postprandial C-peptide AUC After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in postprandial C-peptide AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial C-peptide AUC after the morning meal at baseline minus postprandial C-peptide AUC after the morning meal at endpoint)

  • Change in Postprandial C-peptide AUC Excursion After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in Postprandial C-peptide AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial C-peptide AUC excursion after the morning meal at baseline minus postprandial C-peptide AUC excursion after the morning meal at endpoint)

  • Change in Postprandial Insulin AUC After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in postprandial insulin AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial insulin AUC after the morning meal at baseline minus postprandial insulin AUC after the morning meal at endpoint)

  • Change in Postprandial Insulin AUC Excursion After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in Postprandial insulin AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial insulin AUC excursion after the morning meal at baseline minus postprandial insulin AUC excursion after the morning meal at endpoint)

  • Change in Postprandial Active GLP-1 AUC After the Morning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in Postprandial active GLP-1 AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial active GLP-1 AUC after the morning meal at baseline minus postprandial active GLP-1 AUC after the morning meal at endpoint)

  • Change in Postprandial Active GLP-1 AUC Excursion After the Monrning Meal [ Time Frame: baseline and 8 Weeks ] [ Designated as safety issue: No ]
    Change in Postprandial active GLP-1 AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial active GLP-1 AUC excursion after the morning meal at baseline minus postprandial active GLP-1 AUC excursion after the morning meals at endpoint)

  • Percentage of Patients Experiencing Hypoglycemia (Baseline to Week 4) [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
    Percentage of patients experiencing minor hypoglycemia with a confirmed glucose <54mg/dL

  • Episodes of Hypoglycemia (Baseline to Week 4) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of episodes of hypoglycemia experienced during the first 4 weeks of the study

  • Percentage of Patients Experiencing Hypoglycemia (Week 4 to Week 8) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Percentage of patients experiencing minor hypoglycemia with a confirmed glucose <54mg/dL

  • Episodes of Hypoglycemia (Week 4 to Week 8) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Number of episodes of hypoglycemia experienced between week 4 and week 8 of the study

  • Percentage of Patients Experiencing Hypoglycemia (Overall) [ Time Frame: 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
    Percentage of patients experiencing minor hypoglycemia with a confirmed glucose <54mg/dL

  • Episodes of Hypoglycemia (Overall) [ Time Frame: 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
    Number of episodes of hypoglycemia experienced overall during the study


Enrollment: 83
Study Start Date: August 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence A Drug: exenatide
subcutaneous injection (5mcg or 10mcg), twice a day
Other Name: Byetta
Drug: sitagliptin
oral administration (100mg), once a day in the morning
Other Name: Januvia
Drug: placebo
subcutaneous injection (5mcg or 10mcg), twice a day
Drug: placebo
oral administration (100mg), once a day in the morning
Experimental: Sequence B Drug: exenatide
subcutaneous injection (5mcg or 10mcg), twice a day
Other Name: Byetta
Drug: sitagliptin
oral administration (100mg), once a day in the morning
Other Name: Januvia
Drug: placebo
subcutaneous injection (5mcg or 10mcg), twice a day
Drug: placebo
oral administration (100mg), once a day in the morning

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have type 2 diabetes
  • Has HbA1c 7.0% to 11.0%, at or within 4 weeks prior to Visit 1.
  • Have a fasting glucose concentration <280 mg/dL at Visit 1
  • Have been treated with a stable dose of immediate or extended release metformin for at least 60 days prior to screening OR TZD (rosiglitazone or pioglitazone) for at least 120 days prior to screening.
  • Are between 18 and 70 years of age, inclusive.
  • Have body mass index ≥25 kg/m2 and ≤45 kg/m2.
  • Have a history of stable body weight (not varying by >10% for at least 3 months prior to screening).
  • Can swallow oral study drug capsule, without splitting or crushing.

Exclusion Criteria:

  • Female patients of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause) who meet any of the following criteria:

    • Are breastfeeding.
    • Test positive for pregnancy at the time of screening.
    • Intend to become pregnant during the study.
    • Have not practiced a reliable method of birth control (for example, use of oral contraceptives or Norplant®; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for 3 months prior to screening.
  • Treated with any of the following medications:

    • Insulin, exenatide, pramlintide, sulfonylureas or meglitinides within 3 months of screening
    • Alpha-glucosidase inhibitor within 2 months of screening.
    • Drugs that directly affect gastrointestinal motility, including, but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics.
    • Use of a drug for weight loss (for example, prescription drugs such as orlistat, sibutramine, phentermine, or similar over-the-counter medications) within 3 months prior to Visit 1.
    • Systemic corticosteroids by oral, intravenous, or intramuscular route within 2 months of screening.
  • Have a history of renal transplantation or are currently receiving renal dialysis.
  • Have obvious clinical signs or symptoms of liver disease or acute or chronic hepatitis.
  • Have known active proliferative retinopathy or macular edema expected to need treatment with focal photocoagulation within 3 months.
  • Have an 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.
  • Have had organ transplantation.
  • Have received GLP-1 analogs other than exenatide or DPP-4 inhibitors within the previous 3 months.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00729326

Locations
United States, Texas
Research Site
San Antonio, Texas, United States
Sponsors and Collaborators
Bristol-Myers Squibb
Eli Lilly and Company
Investigators
Study Director: Chief Medical Officer, MD Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00729326     History of Changes
Other Study ID Numbers: H8O-US-GWCV
Study First Received: August 4, 2008
Results First Received: October 12, 2010
Last Updated: September 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Bristol-Myers Squibb:
diabetes
exenatide
sitagliptin
Amylin
Lilly
metformin
thiazolidinedione

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
2,4-thiazolidinedione
Sitagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 21, 2014