Clinical trial NCT02660736: Bioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects
Official title: A Randomized, Double-blind, Single-dose, Crossover Study to Compare Two Albiglutide Drug Products for Bioequivalence in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Albiglutide
Randomized
Pharmacokinetics
GSK716155
Bioequivalence study
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-01-21
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Albiglutide (Alb) is a novel analogue of glucagon-like peptide-1 (GLP-1) has been developed and approved for the treatment of type 2 diabetes mellitus. Currently, lyophilized albiglutide and the diluent are provided in a dual chamber Cartridge (DCC) single-dose pen injector, requiring reconstitution prior to use. A liquid formulation of albiglutide will enable the use of a liquid product in a ready-to-use single dose auto-injector. To support the development of the liquid auto-injector product, this healthy volunteer bioequivalence study will be conducted to compare the liquid drug product to the currently available lyophilized product. This is Phase I, randomized, double-blind, double dummy, single-dose, 2-period crossover study in healthy volunteers. This study will compare the pharmacokinetics and safety of the albiglutide 50 mg liquid drug product with the albiglutide 50 mg commercial lyophilized drug product.


Eligibility criteria: Inclusion Criteria:

* Between 18 and 65 years of age.
* Healthy.
* Subject is a nonsmoker.
* Subject's body mass index (BMI) is \>=18 kilogram/meter square (kg/m\^2) and \<=30 kg/m\^2
* Male or
* Female

Exclusion Criteria:

* Alanine aminotransferase (ALT) \>1.5 x upper limit of normal range (ULN)
* Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities
* QT interval corrected for heart rate according to Fridericia's formula (QTcF) \> 450 millisecond (msec).
* Systolic blood pressure is \>=140 millimeter of mercury (mmHg) at Screening;
* Diastolic blood pressure is \>=90 mmHg at Screening;
* Heart rate is \>100 beats/min at Screening.
* estimated glomerular filtration rate (eGFR) \<=80 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2) (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula) at Screening.
* Fasting triglyceride level \>300 milligram per deciliter (mg/dL) at Screening.
* History of significant cardiovascular or pulmonary dysfunction prior to Screening.
* History of thyroid dysfunction or an abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at Screening.
* History of gastrointestinal surgery that could influence gastric emptying (e.g., gastrectomy, gastric bypass).
* History of pancreatitis.
* Personal or family history of multiple endocrine neoplasia type 2.
* Personal or family history of medullary carcinoma of the thyroid.
* Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days.
* History of regular alcohol consumption within 6 months of the study.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
* Subject has previously received any GLP-1 mimetic compound (eg., exenatide, liraglutide, lixisenatide, dulaglutide).
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* A positive pre-study drug/alcohol screen.
* A positive test for human immunodeficiency virus (HIV) antibody.
* Subject has donated blood in excess of 500 mL within 56 days prior to dosing or intention of donating in the month after completing the study.
* 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 4 new chemical entities within 12 months prior to the first dosing day

Primary outcomes:
measure: Area under the plasma concentration-time curve (AUC) from 0 to the last measurable concentration (AUC 0-t) for albiglutide in session 1 and 2
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
measure: AUC from 0 to infinity (AUC [0-inf]) for albiglutide in session 1 and 2
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
measure: Peak plasma concentration (Cmax) for albiglutide in session 1 and 2
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Secondary outcomes:
measure: Time to maximal concentration (Tmax) for albiglutide in session 1 and 2
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
measure: Clearance (CL/F) for albiglutide in session 1 and 2.
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
measure: Volume of distribution (V/F) for albiglutide in session 1 and 2
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
measure: Number of subjects with adverse events (AE) and clinical observations as a measure of safety and tolerability
timeFrame: Up to 21 weeks
measure: Safety as assessed by 12-lead electrocardiogram (ECG)
timeFrame: Screening, Day -1, Day 4, and Day 35 in both sessions 1 and 2
measure: Safety as assessed by systolic, diastolic blood pressure, and pulse rate measurements
timeFrame: Up to 21 weeks
measure: Immunogenicity as assessed by enzyme-linked immunosorbent assay (ELISA) and hypersensitivity reactions.
timeFrame: Day 1 in both sessions and Day 13 in session 1 and follow-up visit
measure: Half-life (T1/2) for albiglutide in session 1 and 2
timeFrame: Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2.
measure: Composite of hematology parameters as a measure of safety
timeFrame: Up to 21 weeks
measure: Composite of clinical chemistry parameters as a measure of safety
timeFrame: Up to 21 weeks
measure: Composite of urinalysis parameters as a measure of safety
timeFrame: Up to 21 Weeks
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Shaddinger BC, Vlasakakis G, Soffer J, Thorpe KM, Hatch D, Nino AJ. A Randomized, Double-Blind, Single-Dose, Crossover Study to Demonstrate the Bioequivalence of 2 Formulations of Albiglutide in Healthy Adult Participants. Clin Pharmacol Drug Dev. 2019 Apr;8(3):361-370. doi: 10.1002/cpdd.606. Epub 2018 Jul 31.