Exendin(9-39)Amide as a Glucagon-like Peptide-1 (GLP-1) Receptor Antagonist in Humans

• Status: Completed
• Trial end date: 2007-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the dose of the GLP-1 receptor antagonist exendin(9-39) which blocks the insulinotropic action of synthetic GLP-1 by at least 95%.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Ludwig-Maximilians - University of Munich
• Collaborators: German Research Foundation; Merck Sharp & Dohme Corp.
• Treatments: Glucagon; Glucagon-Like Peptide 1

Criteria

Inclusion Criteria:

• Male or female (postmenopausal, surgically sterile or using double-barrier method of contraception) healthy volunteers

• Age 18-65 years

• Hemoglobin A1c (HbA1c) < 6%

• Body mass index (BMI) < 30 kg/m2

• Must have a fasting blood glucose below 100 mg/dl at screening and on all study days

• Able to provide written informed consent prior to study participation

• Able to communicate well with the investigator and comply with the requirements of the study

Exclusion Criteria:

• Diabetes mellitus

• Fasting triglycerides > 5.1 mmol/L (> 450 mg/dL) within the past 4 weeks.

• Treatment with systemic steroids and thyroid hormone

• Patients with any history of gastrointestinal surgery, e.g. partial bowel resections, partial gastric resections, etc.

• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.

• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.

• Significant illness within the two weeks prior to dosing.

• Past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome.

• History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study. The investigator should be guided by evidence of any of the following:

• history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding

• history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection

• history or clinical evidence of pancreatic injury or pancreatitis

• history or presence of impaired renal function as indicated by abnormal creatinine or urea values or abnormal urinary constituents (e.g., albuminuria)

• evidence of urinary obstruction or difficulty in voiding at screening

• Polymorphonuclears < 1500/µL at inclusion or platelet count < 100,000/μL at screening and baseline.

• Evidence of liver disease as indicated by abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin.

• History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.