Clinical trial NCT02683746: Safety and Efficacy Study of Albiglutide Liquid Drug Product in Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Pharmacodynamics
Safety
Albiglutide
Tolerability
Type 2 Diabetes Mellitus
Efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-02-17
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: Up to Week 26
measure: Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC)
timeFrame: Up to Week 26
measure: Number of Participants With Hematology Parameters of PCC
timeFrame: Up to Week 26
measure: Number of Participants With Vital Signs of PCC
timeFrame: Up to Week 34
measure: Number of Participants With Electrocardiogram (ECG) Parameters of PCC
timeFrame: Up to Week 26
measure: Number of Participants With Positive Result for Anti-albiglutide Antibody
timeFrame: Up to Week 34
measure: Number of Participants With Injection Site Reactions (ISR)
timeFrame: Up to Week 34
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
timeFrame: Baseline and Week 26
measure: Change From Baseline in HbA1c Over Time
timeFrame: Baseline and up to Week 26
measure: Change From Baseline in FPG Over Time
timeFrame: Baseline and up to Week 26
measure: Trough Plasma Concentration of Albiglutide Over Time
timeFrame: Pre-dose at Week 12 and Week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: Glendale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Canyon Country
country: United States
facility: GSK Investigational Site
state: California
city: Chula Vista
country: United States
facility: GSK Investigational Site
state: California
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Lomita
country: United States
facility: GSK Investigational Site
state: California
city: Oceanside
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Spring Valley
country: United States
facility: GSK Investigational Site
state: California
city: Tustin
country: United States
facility: GSK Investigational Site
state: California
city: Van Nuys
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Littleton
country: United States
facility: GSK Investigational Site
state: Colorado
city: Bradenton
country: United States
facility: GSK Investigational Site
state: Florida
city: Brooksville
country: United States
facility: GSK Investigational Site
state: Florida
city: Clearwater
country: United States
facility: GSK Investigational Site
state: Florida
city: Fleming Island
country: United States
facility: GSK Investigational Site
state: Florida
city: Hallandale Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Conyers
country: United States
facility: GSK Investigational Site
state: Georgia
city: Snellville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Meridian
country: United States
facility: GSK Investigational Site
state: Idaho
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Elgin
country: United States
facility: GSK Investigational Site
state: Illinois
city: Evansville
country: United States
facility: GSK Investigational Site
state: Indiana
city: Topeka
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Lake Charles
country: United States
facility: GSK Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Kalamazoo
country: United States
facility: GSK Investigational Site
state: Michigan
city: Troy
country: United States
facility: GSK Investigational Site
state: Michigan
city: Chesterfield
country: United States
facility: GSK Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: New Hyde Park
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Shelby
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Maumee
country: United States
facility: GSK Investigational Site
state: Ohio
city: Norwood
country: United States
facility: GSK Investigational Site
state: Ohio
city: Perrysburg
country: United States
facility: GSK Investigational Site
state: Ohio
city: Altoona
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Anderson
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Arlington
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Katy
country: United States
facility: GSK Investigational Site
state: Texas
city: Pharr
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Schertz
country: United States
facility: GSK Investigational Site
state: Texas
city: Spring
country: United States
facility: GSK Investigational Site
state: Texas
city: Murray
country: United States
facility: GSK Investigational Site
state: Utah
city: Federal Way
country: United States
facility: GSK Investigational Site
state: Washington
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.