Safety and Efficacy Study of Albiglutide Liquid Drug Product in Type 2 Diabetes Mellitus

NCT ID: NCT02683746

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 308 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-16
• Study Completion Date: 2017-05-15

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Albiglutide active LAI plus Placebo lyophilized DCC PI

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.

Group Type: EXPERIMENTAL

Lyophilized albiglutide DCC pen injector matching placebo

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Albiglutide lyophilized DCC PI plus Placebo LAI

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.

Group Type: EXPERIMENTAL

Lyophilized albiglutide DCC pen injector

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Chandler, Arizona, United States

GSK Investigational Site

Glendale, Arizona, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Anaheim, California, United States

GSK Investigational Site

Canyon Country, California, United States

GSK Investigational Site

Chula Vista, California, United States

GSK Investigational Site

Fresno, California, United States

GSK Investigational Site

Lomita, California, United States

GSK Investigational Site

Oceanside, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Spring Valley, California, United States

GSK Investigational Site

Tustin, California, United States

GSK Investigational Site

Van Nuys, California, United States

GSK Investigational Site

Walnut Creek, California, United States

GSK Investigational Site

Littleton, Colorado, United States

GSK Investigational Site

Bradenton, Florida, United States

GSK Investigational Site

Brooksville, Florida, United States

GSK Investigational Site

Clearwater, Florida, United States

GSK Investigational Site

Fleming Island, Florida, United States

GSK Investigational Site

Hallandale, Florida, United States

GSK Investigational Site

Hialeah, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

New Port Richey, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

St. Petersburg, Florida, United States

GSK Investigational Site

Conyers, Georgia, United States

GSK Investigational Site

Snellville, Georgia, United States

GSK Investigational Site

Meridian, Idaho, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Elgin, Illinois, United States

GSK Investigational Site

Evansville, Indiana, United States

GSK Investigational Site

Topeka, Kansas, United States

GSK Investigational Site

Lexington, Kentucky, United States

GSK Investigational Site

Lake Charles, Louisiana, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

Kalamazoo, Michigan, United States

GSK Investigational Site

Troy, Michigan, United States

GSK Investigational Site

Chesterfield, Missouri, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

New Hyde Park, New York, United States

GSK Investigational Site

Greensboro, North Carolina, United States

GSK Investigational Site

Shelby, North Carolina, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Maumee, Ohio, United States

GSK Investigational Site

Norwood, Ohio, United States

GSK Investigational Site

Perrysburg, Ohio, United States

GSK Investigational Site

Altoona, Pennsylvania, United States

GSK Investigational Site

Anderson, South Carolina, United States

GSK Investigational Site

Columbia, South Carolina, United States

GSK Investigational Site

Arlington, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Katy, Texas, United States

GSK Investigational Site

Pharr, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Schertz, Texas, United States

GSK Investigational Site

Spring, Texas, United States

GSK Investigational Site

Murray, Utah, United States

GSK Investigational Site

Federal Way, Washington, United States

GSK Investigational Site

Spokane, Washington, United States

GSK Investigational Site

Tacoma, Washington, United States

Countries

United States

References

Shaddinger BC, Soffer J, Vlasakakis G, Shabbout M, Weston C, Nino A. Efficacy and safety of an albiglutide liquid formulation compared with the lyophilized formulation: A 26-week randomized, double-blind, repeat-dose study in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2019 Jun;152:125-134. doi: 10.1016/j.diabres.2019.04.018. Epub 2019 Apr 18.

Reference Type: BACKGROUND

PMID: 31004676 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

200952

Identifier Type: -

Identifier Source: org_study_id