Safety and Efficacy Study of Albiglutide Liquid Drug Product in Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lyophilized albiglutide DCC pen injector; Lyophilized albiglutide DCC pen injector matching placebo; Albiglutide liquid auto-injector; Albiglutide liquid auto-injector matching placebo
Intervention description: 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.; A fixed-dose, fully disposable pen injector system with a prefilled DCC containing matching placebo delivering an injection volume of 0.5mL; 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.; 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 MeSH terms: rGLP-1 protein; Glucagon-Like Peptide 1
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 308.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Pharmacodynamics; Safety; Albiglutide; Tolerability; Type 2 Diabetes Mellitus; Efficacy

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).