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

NCT02683746 | Completed Phase 3 Results

• 1 other identifier: 200952
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 70

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

Keywords

Pharmacodynamics; Safety; Albiglutide; Tolerability; Type 2 Diabetes Mellitus; Efficacy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26

  Blood samples will be collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a mixed-effect model with repeated measures (MMRM) method. The primary analysis will include all HbA1c values collected at scheduled visits from Week 4 up to Week 26. This will include values after hyperglycemia rescue and discontinuation from investigational product. Imputation under the non-inferiority null hypothesis for missing data will be incorporated.

  Baseline and Week 26

Secondary Outcomes (11)

• Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs)

  Up to Week 26

• Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC)

  Up to Week 26

• Number of Participants With Hematology Parameters of PCC

  Up to Week 26

• Number of Participants With Vital Signs of PCC

  Up to Week 34

• Number of Participants With Electrocardiogram (ECG) Parameters of PCC

  Up to Week 26

Study Arms (2)

Albiglutide active LAI plus Placebo lyophilized DCC PI

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.

Drug: Lyophilized albiglutide DCC pen injector matching placebo; Drug: Albiglutide liquid auto-injector

Albiglutide lyophilized DCC PI plus Placebo LAI

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.

Drug: Lyophilized albiglutide DCC pen injector; Drug: Albiglutide liquid auto-injector matching placebo

Interventions

Lyophilized albiglutide DCC pen injector 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 lyophilized DCC PI plus Placebo LAI

Lyophilized albiglutide DCC pen injector matching placebo DRUG

A fixed-dose, fully disposable pen injector system with a prefilled DCC containing matching placebo delivering an injection volume of 0.5mL

Albiglutide active LAI plus Placebo lyophilized DCC PI

Albiglutide liquid auto-injector 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 active LAI plus Placebo lyophilized DCC PI

Albiglutide liquid auto-injector matching placebo 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.

Albiglutide lyophilized DCC PI plus Placebo LAI

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (70)

GSK Investigational Site

Birmingham, Alabama, 35216, United States

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GSK Investigational Site

Birmingham, Alabama, 35235, United States

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GSK Investigational Site

Chandler, Arizona, 85224, United States

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GSK Investigational Site

Glendale, Arizona, 85306, United States

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Phoenix, Arizona, 85018, United States

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Anaheim, California, 92801, United States

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Canyon Country, California, 91351, United States

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Chula Vista, California, 91911, United States

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Fresno, California, 93720, United States

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Lomita, California, 90717, United States

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Oceanside, California, 92056, United States

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Sacramento, California, 95821, United States

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San Diego, California, 92120, United States

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Spring Valley, California, 91978, United States

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Tustin, California, 92780, United States

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Van Nuys, California, 91405, United States

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Walnut Creek, California, 94598, United States

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Littleton, Colorado, 80128, United States

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Bradenton, Florida, 34208, United States

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Brooksville, Florida, 34601, United States

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Clearwater, Florida, 33765-2616, United States

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Fleming Island, Florida, 32003, United States

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Hallandale, Florida, 33009, United States

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Hialeah, Florida, 33016, United States

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Miami, Florida, 33156, United States

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Miami, Florida, 33176, United States

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New Port Richey, Florida, 34652, United States

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Orlando, Florida, 32825, United States

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St. Petersburg, Florida, 33709, United States

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Conyers, Georgia, 30094, United States

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Snellville, Georgia, 30078, United States

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Meridian, Idaho, 83642, United States

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Chicago, Illinois, 60612, United States

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Elgin, Illinois, 60124, United States

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Evansville, Indiana, 47714, United States

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Topeka, Kansas, 66606, United States

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Lexington, Kentucky, 40503, United States

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Lake Charles, Louisiana, 70601, United States

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New Orleans, Louisiana, 70119, United States

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Kalamazoo, Michigan, 49009, United States

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Troy, Michigan, 48098, United States

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Chesterfield, Missouri, 63017, United States

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St Louis, Missouri, 63141, United States

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Las Vegas, Nevada, 89123, United States

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Albuquerque, New Mexico, 87102, United States

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New Hyde Park, New York, 11042, United States

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Greensboro, North Carolina, 27405, United States

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Shelby, North Carolina, 28150, United States

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Columbus, Ohio, 43201, United States

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Maumee, Ohio, 43537-9402, United States

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Norwood, Ohio, 45212, United States

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Perrysburg, Ohio, 43551, United States

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Altoona, Pennsylvania, 16602, United States

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Anderson, South Carolina, 29621, United States

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Columbia, South Carolina, 29204, United States

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Arlington, Texas, 76012, United States

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Dallas, Texas, 75230, United States

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GSK Investigational Site

Houston, Texas, 77051, United States

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GSK Investigational Site

Houston, Texas, 77058, United States

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GSK Investigational Site

Houston, Texas, 77074, United States

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GSK Investigational Site

Katy, Texas, 77079, United States

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GSK Investigational Site

Pharr, Texas, 78577, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

San Antonio, Texas, 78231, United States

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GSK Investigational Site

Schertz, Texas, 78154, United States

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GSK Investigational Site

Spring, Texas, 77379, United States

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GSK Investigational Site

Murray, Utah, 84123, United States

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GSK Investigational Site

Federal Way, Washington, 98003, United States

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GSK Investigational Site

Spokane, Washington, 99208, United States

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GSK Investigational Site

Tacoma, Washington, 98405, United States

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Related Publications (1)

• 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.

  PMID: 31004676 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 17, 2016
• Study Start: March 16, 2016
• Primary Completion: April 3, 2017
• Study Completion: May 15, 2017
• Last Updated: July 23, 2019
• Results First Posted: May 30, 2018

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (70)