Feasibility Study of Exenatide by Continuous Subcutaneous Infusion

An Open-Label Exploratory Study to Investigate the Feasibility of Administering Exenatide by Continuous Subcutaneous Infusion to Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Exenatide

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Male/females aged between 18 and 60 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures and objectives.
• 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%).

Exclusion Criteria

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide infusion in Part A; Subjects in Part A will receive exenatide as a subcutaneous infusion at a constant rate for 24 hours.	Drug: Exenatide; Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.
Experimental: Exenatide infusion in Part B; Subjects in Part B will receive exenatide with daily increases in the infusion rate.	Drug: Exenatide; Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of interruptions or deviations from prescribed exenatide infusion in Part A	To investigate the feasibility of administering exenatide via continuous subcutaneous infusion	2 days
Characterization of interruptions or deviations from prescribed exenatide infusion in Part B	To investigate the feasibility of administering exenatide via continuous subcutaneous infusion	8 days
Infusion rate adjustments when nausea/vomiting occurs in Part B	To investigate the feasibility of administering exenatide via continuous subcutaneous infusion. Infusion rate adjustment will be done to achieve tolerable infusion rate when nausea/vomiting occurs	8 days
Number of participants with adverse events (AEs) in Part A	AEs will be collected from the Day -1 and until the follow-up contact. AE data will be collected to evaluate the ability to monitor and maintain acceptable safety	17 days
Number of participants with AEs in Part B	AEs will be collected from the Day -1 and until the follow-up contact. AE data will be collected to evaluate the ability to monitor and maintain acceptable safety	23 days
Laboratory parameter assessment in Part A	Laboratory parameters include: hematology, clinical chemistry, and urinalysis	17 days
Laboratory parameter assessment in Part B	Laboratory parameters include: hematology, clinical chemistry, and urinalysis	23 days
Vital sign assessment in Part A	Vital signs measurement include: systolic and diastolic blood pressure, and pulse rate	17 days
Vital sign assessment in Part B	Vital signs measurement include: systolic and diastolic blood pressure, and pulse rate	23 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile of exenatide in Part A	PK parameters include: area under concentration time curve from time 0 to 24 hours (AUC0 to24), maximum observed concentration from time 0 to 24 hours (Cmax0 to 24), and average concentration from time 0 to 24 hours (Cavg0 to 24) versus time	PK samples will be collected at pre-dose, and at 0.5, 1, 2, 4, 6, 10, 14, 24, and 26 hours post dose.
Pharmacokinetic (PK) profile of exenatide in Part B	PK parameters include: AUC0-24, Cmax0 to 24, and Cavg0 to 24 versus time for each of 7 days and AUC0 to 168, Cmax0 to 168, and Cavg0 to 168 versus time over entire infusion period.	8 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Parexel

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Nausea; exenatide; subcutaneous infusion
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: 200016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 200016
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register