Overview

This trial is active, not recruiting.

Condition diabetes mellitus, type 2
Treatments lyophilized albiglutide dcc pen injector, lyophilized albiglutide dcc pen injector matching placebo, albiglutide liquid auto-injector, albiglutide liquid auto-injector matching placebo
Phase phase 3
Sponsor GlaxoSmithKline
Start date March 2016
End date May 2017
Trial size 300 participants
Trial identifier NCT02683746, 200952

Summary

This is a phase III, randomized, double-blind, multicenter, parallel group, repeat-dose, study of 26 weeks duration to evaluate the efficacy, safety, tolerability and pharmacodynamic response of albiglutide liquid drug product relative to the commercial lyophilized drug product. The study will specifically evaluate the potential for immunogenicity (example [e.g.] incidences of anti-drug antibodies [ADA]) and injection site reactions (ISRs).

Albiglutide is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently long half-life to permit once a week injection. 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 commercialization of a liquid product in a single dose, ready-to-use prefilled syringe in an auto-injector.

The primary hypothesis of this study is to test that liquid drug product will provide glycemic control (as measured by HbA1c change from baseline) non-inferior to lyophilized drug product for a period of 26 weeks of treatment in subjects with T2DM.

This study will comprise of 3 study periods : screening (2 weeks), treatment (26 weeks) and for those subjects not entering the extension study a follow-up period (8 weeks). Approximately 300 subjects will be randomized in a 1:1 ratio to either Albiglutide active liquid auto-injector (LAI) plus Placebo lyophilized DCC pen injector (lyophilized DCC PI); or, Albiglutide lyophilized DCC PI plus Placebo LAI.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Subjects will receive 30 milligrams (mg) of albiglutide liquid drug product via auto injector and matching placebo via lyophilized DCC pen injector for 4 weeks. The dose will then be up-titrated to 50mg albiglutide for the remaining 22 weeks of the study. The study treatment will be administered once weekly by subcutaneous injection in the abdomen, thigh, or upper arm.
lyophilized albiglutide dcc pen injector matching placebo
A fixed-dose, fully disposable pen injector system with a prefilled DCC containing matching placebo delivering an injection volume of 0.5mL
albiglutide liquid auto-injector
A fixed-dose, single use, disposable auto-injector containing albiglutide liquid (30mg or 50mg) in a prefilled glass syringe. The auto-injector delivers the albiglutide liquid in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.
(Experimental)
Subjects will receive 30mg of albiglutide lyophilized drug product via DCC pen injector and matching placebo via auto injector for 4 weeks. The dose will then be up-titrated to 50mg albiglutide for the remaining 22 weeks of the study. The study treatment will be administered once weekly by subcutaneous injection in the abdomen, thigh, or upper arm.
lyophilized albiglutide dcc pen injector
A fixed-dose, fully disposable pen injector system with a prefilled dual chamber glass cartridge (DCC) containing lyophilized albiglutide (30mg or 50mg) delivering an injection volume of 0.5mL.
albiglutide liquid auto-injector matching placebo
A fixed-dose, single use, disposable auto-injector containing matching placebo in a prefilled glass syringe. The auto-injector delivers the matching placebo in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.

Primary Outcomes

Measure
Change from baseline in glycated hemoglobin (HbA1c) at Week26
time frame: Baseline and Week 26

Secondary Outcomes

Measure
Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs)
time frame: Maximum of 36 weeks
Safety as assessed by physical examination
time frame: Maximum of 36 weeks
Number of Participants With Abnormal Laboratory Values
time frame: Maximum of 28 weeks
Safety as assessed by blood pressure measurements
time frame: Maximum of 36 weeks
Safety as assessed by pulse rate measurement
time frame: Maximum of 36 weeks
Safety as assessed by 12-lead electrocardiogram (ECG)
time frame: Maximum of 28 weeks
Anti-albiglutide antibody production
time frame: Maximum of 34 weeks
Rate of injection site reactions (ISRs) over time.
time frame: Maximum of 34 weeks
Change from baseline in fasting plasma glucose (FPG) at Week 26
time frame: Baseline and Week 26
Change from baseline in HbA1c over time
time frame: Baseline and up to Week 34
Change from baseline in FPG over time
time frame: Baseline and up to Week 34
Trough concentrations of albiglutide
time frame: Week 13 and Week 26

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - 18 to 80 years of age inclusive - Historical diagnosis of type 2 diabetes mellitus (T2DM) (at least 3 months), experiencing inadequate glycemic control on current regimen of diet and exercise or on a stable maximal tolerated dose of metformin, maintained for approximately 8 weeks prior to screening. - HbA1c >=7.0 percent (%) and <=10%. - Hemoglobin >=11 grams per deciliter (g/dL) (>=110 grams per liter [g/L]) for males and >=10 g/dL (>=100 g/L) for females. - Body mass index <=40 kilograms per squared meter (kg/m^2) - Male or female - Able and willing to provide informed consent. Exclusion Criteria: - Type 1 diabetes mellitus - History of cancer that has not been in full remission for at least 3 years before screening. (A history of squamous cell or basal cell carcinoma of the skin or treated cervical intra-epithelial neoplasia I or II is allowed). - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. - History of acute or chronic pancreatitis. - History of thyroid dysfunction or an abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at screening. - Severe gastroparesis, i.e., requiring regular therapy within 6 months before screening. - History of significant gastrointestinal (GI) surgery that in the opinion of the investigator is likely to significantly affect upper GI or pancreatic function - History of severe hypoglycemia unawareness - Diabetic complications or any other clinically significant abnormality . - Clinically significant Cardiovascular (CV) and/or cerebrovascular disease within 3 months before screening - QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 470 milliseconds (msec). - ALT >2.5x upper limit of the normal range (ULN) or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). - Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). - Estimated glomerular filtration rate (eGFR) <=30 milliliter (mL)/minute (min)/1.73 squared meter (m^2) (calculated using the Modification of Diet in Renal Disease [MDRD] formula) at screening. - Fasting triglyceride level >750 milligrams per deciliter (mg/dL) at screening. - Hemoglobinopathy that may affect proper interpretation of HbA1c. - Medical or psychiatric disorders that would preclude effective participation in study. - Use of oral or systemically injected glucocorticoids within the 3 months before randomization or high likelihood of a requirement for prolonged treatment (>1 week) in the 6 months following randomization. - Use of dipeptidyl peptidase-IV inhibitors within the 3 months before randomization. - History of alcohol or substance abuse within one year before screening. - Known allergy to albiglutide or any product components (including yeast and human albumin), any other glucagon-like peptide-1 (GLP-1) analogue, or other study medication's excipients OR other contraindications (per the prescribing information) for the use of potential study medications. - A positive pre-study drug/alcohol screen. - A positive test for human immunodeficiency virus (HIV) antibody. - 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).

Additional Information

Official title A Repeat-dose Study in Subjects With Type 2 Diabetes Mellitus to Assess the Efficacy, Safety, Tolerability and Pharmacodynamics, of Albiglutide Liquid Drug Product
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.