Feasibility Study of Exenatide by Continuous Subcutaneous Infusion

NCT ID: NCT01857895

Last Updated: 2017-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-16
• Study Completion Date: 2013-11-01

Brief Summary

This is an open-label study to investigate the feasibility of administering exenatide by continuous subcutaneous infusion to healthy subjects. Study will consist of two parts i.e. Part A and B. In Part A 2 healthy subjects will receive exenatide infusion over 24 hours followed by a follow-up visit 10 to 14 days after discharge from clinic. In Part B approximately 6 healthy subjects will receive subcutaneous infusions of exenatide for maximum of 7 days followed by a follow-up visit 10 to 14 days after discharge from clinic.

Conditions

Obesity

Keywords

Nausea; subcutaneous infusion; exenatide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exenatide infusion in Part A

Subjects in Part A will receive exenatide as a subcutaneous infusion at a constant rate for 24 hours.

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: DRUG

Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.

Exenatide infusion in Part B

Subjects in Part B will receive exenatide with daily increases in the infusion rate.

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: DRUG

Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.

Interventions

Exenatide

Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male/females aged between 18 and 60 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Body Mass Index within the range 18 to 35 kilograms/meter squared (kg/m^2) inclusive.
• A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone > 40 milli international unit/mililiter (mL) and estradiol <40 picogram/mL (<147 picomoles/Liter) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
• Child-bearing potential females must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until follow up visit.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Based on QT interval corrected for heart rate (QTc) of single electrocardiogram (ECG): QTc by Fridericia's formula <450 millisecond (msec).
• Aspartate aminotransferase and Alanine aminotransferase <2x upper limit of normal (ULN); alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Subjects with a personal or family history of thyroid carcinoma or Type 2 Familial Endocrine Neoplasia.
• History of uncorrected thyroid dysfunction or an abnormal thyroid functions as assessed by thyroid stimulating hormones.
• Subjects with a history of severe gastrointestinal disease, or abnormal renal function.
• Subjects with previous exposure to a Glucagon-like peptide-1 mimetic.
• History of chronic or acute pancreatitis. Note: Subjects with a lipase value above 1.5X ULN at screening are excluded.
• Current or chronic history of liver disease, or hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.

Criteria Based Upon Diagnostic Assessments

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive pre-study drug/alcohol screen.
• A subject with a positive urine cotinine test result will be excluded from the study unless in the judgment of the Investigator the subject will be able to abstain from using tobacco for the duration of the in-house period of the study.
• A positive test for human immuno virus antibody.

Other Criteria

• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Baltimore, Maryland, United States

Countries

United States

References

Vlasakakis G, Johnson SL, Lin J, Yao X, Gruenloh CJ, Chism JP, Nunez DJ. Pharmacokinetics and Tolerability of Exenatide Delivered by 7-Day Continuous Subcutaneous Infusion in Healthy Volunteers. Adv Ther. 2015 Jul;32(7):650-61. doi: 10.1007/s12325-015-0222-4. Epub 2015 Jul 10.

Reference Type: DERIVED

PMID: 26160357 (View on PubMed)

Study Documents

Document Type: Study Protocol

View Document

Document Type: Dataset Specification

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Individual Participant Data Set

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Document Type: Clinical Study Report

View Document

Other Identifiers

200016

Identifier Type: -

Identifier Source: org_study_id