safety and efficacy study of albiglutide liquid drug product in type 2 diabetes mellitus

Conditions: Diabetes Mellitus, Type 2

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).

Keywords: pharmacodynamics safety albiglutide tolerability type 2 diabetes mellitus efficacy