Bioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Placebo Liquid Auto-injector; Drug: Albiglutide Lyophilized DCC Pen Injector; Drug: Placebo Lyophilized DCC Pen injector; Drug: Albiglutide Liquid Auto-injector

Study type: Interventional

Funder types: Industry

Identifiers

NCT02660736

201287

Details and patient eligibility

About

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.

Enrollment: 59 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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59 participants in 2 patient groups

Regimen AB

Experimental group

Description:

Subjects will be receive Regimen A treatment in Session 1 followed by Regimen B treatment in Session 2. Regimen A: 50 mg Albiglutide Liquid Auto-injector + Placebo lyophilized DCC Pen injector. Regimen B: 50 mg Albiglutide lyophilized DCC Pen injector + Placebo Liquid Auto-injector. A minimum of an 8-week washout period between study treatment administration of Session 1 and Session 2.

Treatment:

Drug: Albiglutide Lyophilized DCC Pen Injector

Drug: Placebo Liquid Auto-injector

Drug: Albiglutide Liquid Auto-injector

Drug: Placebo Lyophilized DCC Pen injector

Regimen BA

Experimental group

Description:

Subjects will be receive Regimen B treatment in Session 1 followed by Regimen A treatment in Session 2. Regimen A: 50 mg Albiglutide Liquid Auto-injector + Placebo lyophilized DCC Pen injector. Regimen B: 50 mg Albiglutide lyophilized DCC Pen injector + Placebo Liquid Auto-injector. A minimum of an 8-week washout period between study treatment administration of Session 1 and Session 2.

Treatment:

Drug: Albiglutide Lyophilized DCC Pen Injector

Drug: Placebo Liquid Auto-injector

Drug: Albiglutide Liquid Auto-injector

Drug: Placebo Lyophilized DCC Pen injector