Bioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Albiglutide Liquid Auto-injector; Drug: Albiglutide Lyophilized DCC Pen Injector; Drug: Placebo Liquid Auto-injector; Drug: Placebo Lyophilized DCC Pen injector

• Registration Number: NCT02660736
• Lead Sponsor: GlaxoSmithKline

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-01-11
• Study First Submitted QC: 2016-01-18
• Study First Posted: 2016-01-21
• Study Start: 2016-02
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-08
• Last Update Posted: 2016-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Regimen AB	Placebo Liquid Auto-injector	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.
Regimen AB	Placebo Lyophilized DCC Pen injector	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.
Regimen BA	Placebo Liquid Auto-injector	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.
Regimen BA	Placebo Lyophilized DCC Pen injector	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.
Regimen AB	Albiglutide Lyophilized DCC Pen Injector	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.
Regimen BA	Albiglutide Lyophilized DCC Pen Injector	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.
Regimen AB	Albiglutide Liquid Auto-injector	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.
Regimen BA	Albiglutide Liquid Auto-injector	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.

Primary Outcome Measures

Name	Time	Method
AUC from 0 to infinity (AUC [0-inf]) for albiglutide in session 1 and 2	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2	PK blood samples will be collected for determination of albiglutide plasma concentrations AUC(0-inf).
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	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2	PK blood samples will be collected for determination of albiglutide plasma concentrations and (AUC 0-t).
Peak plasma concentration (Cmax) for albiglutide in session 1 and 2	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2	PK blood samples will be collected for determination of albiglutide Cmax.

Secondary Outcome Measures

Name	Time	Method
Time to maximal concentration (Tmax) for albiglutide in session 1 and 2	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2	PK blood samples will be collected for determination of albiglutide Tmax.
Number of subjects with adverse events (AE) and clinical observations as a measure of safety and tolerability	Up to 21 weeks	AE will be collected during the study. Intensity of AE will be captured
Safety as assessed by systolic, diastolic blood pressure, and pulse rate measurements	Up to 21 weeks	Systolic and diastolic pressure and pulse rate will be measured at specified time point
Immunogenicity as assessed by enzyme-linked immunosorbent assay (ELISA) and hypersensitivity reactions.	Day 1 in both sessions and Day 13 in session 1 and follow-up visit	Immunogenicity serum samples will be collected at specified time points to assess the presence of anti-drug antibodies through enzyme-linked immunosorbent assay (ELISA) method.
Composite of hematology parameters as a measure of safety	Up to 21 weeks	The following hematology parameters will be measured: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, Reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH Concentration, white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
Half-life (T1/2) for albiglutide in session 1 and 2	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2.	PK blood samples will be collected for determination of albiglutide T1/2.
Clearance (CL/F) for albiglutide in session 1 and 2.	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2	PK blood samples will be collected for determination of albiglutide CL/F
Volume of distribution (V/F) for albiglutide in session 1 and 2	Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2	PK blood samples will be collected for determination of albiglutide V/F
Safety as assessed by 12-lead electrocardiogram (ECG)	Screening, Day -1, Day 4, and Day 35 in both sessions 1 and 2	Single 12-lead ECGs will be obtained at the specified time points during the study using an ECG machine that automatically calculates the heart rate and other measures.
Composite of clinical chemistry parameters as a measure of safety	Up to 21 weeks	The following clinical chemistry parameters will be measured: blood urea nitrogen (BUN), creatinine, fasting glucose, uric acid, thyroid-stimulating hormone (TSH), potassium, sodium, calcium, phosphorus, magnesium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, gamma glutamyl transferase (GGT), chloride, total and direct bilirubin, total protein, albumin, total carbon dioxide, and fasting triglycerides.
Composite of urinalysis parameters as a measure of safety	Up to 21 Weeks	The following urinalysis parameters will be measured: specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones by dipstick; microscopic examination (if blood or protein is abnormal), microalbumin, creatinine, albumin/creatinine ratio, blood, leukocyte esterase, and nitrites.

Trial Locations

Locations (1)

GSK Investigational Site; 🇺🇸 Austin, Texas, United States