Obesity
Conditions
Keywords
Nausea, subcutaneous infusion, exenatide
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.
Interventions
DRUGExenatide
Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.
Sponsors
Parexel
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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%).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vital sign assessment in Part B | 23 days | Vital signs measurement include: systolic and diastolic blood pressure, and pulse rate |
| Laboratory parameter assessment in Part B | 23 days | Laboratory parameters include: hematology, clinical chemistry, and urinalysis |
| Vital sign assessment in Part A | 17 days | Vital signs measurement include: systolic and diastolic blood pressure, and pulse rate |
| Characterization of interruptions or deviations from prescribed exenatide infusion in Part A | 2 days | To investigate the feasibility of administering exenatide via continuous subcutaneous infusion |
| Characterization of interruptions or deviations from prescribed exenatide infusion in Part B | 8 days | To investigate the feasibility of administering exenatide via continuous subcutaneous infusion |
| Infusion rate adjustments when nausea/vomiting occurs in Part B | 8 days | 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 |
| Number of participants with adverse events (AEs) in Part A | 17 days | 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 |
| Number of participants with AEs in Part B | 23 days | 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 |
| Laboratory parameter assessment in Part A | 17 days | Laboratory parameters include: hematology, clinical chemistry, and urinalysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) profile of exenatide in Part B | 8 days | 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. |
| Pharmacokinetic (PK) profile of exenatide in Part A | PK samples will be collected at pre-dose, and at 0.5, 1, 2, 4, 6, 10, 14, 24, and 26 hours post dose. | 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 |
Countries
United States
Outcome results
None listed