Safety and Efficacy of Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Albiglutide; Insulin Glargine and Insulin Lispro
Intervention description: Albiglutide is intended for self-administration as a SC injection. It is provided as a fixed dose of 30 mg of albiglutide or 50 mg of albiglutide in a 0.5 mL injection volume, fully disposable pen injector; Insulin glargine and insulin lispro will be provided as injection pens for SC injection
Intervention MeSH terms: Insulin; Insulin Glargine; Insulin Lispro; rGLP-1 protein
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 814.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: switch study; albiglutide; glucagon-like peptide-1 receptor agonist; Type 2 diabetes mellitus; basal-bolus insulin therapy

Summary:

      This Phase IIIb, randomized, open-label, parallel group, active control, multicenter, treat
      to-target study of 26 weeks' treatment duration will evaluate the efficacy and safety of
      once-weekly albiglutide as replacement of prandial insulin in subjects with type 2 diabetes
      mellitus (T2DM) failing to achieve adequate glycemic control on their current basal bolus
      insulin regimen (with or without metformin). Approximately 794 subjects will be randomly
      assigned in a 1:1 ratio to 1 of 2 treatment groups: albiglutide + insulin glargine (with
      insulin lispro discontinuation at Week 4) (with or without metformin) or to intensification
      of insulin glargine + insulin lispro (with or without metformin). The study will comprise 4
      study periods : Screening (2 weeks), Standardization (4 weeks), Treatment (26 weeks), and
      Post treatment Follow up (4 weeks). The total duration of a subject's participation will be
      approximately 36 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, 18 years of age or older (inclusive at the time of Screening) with
             T2DM

          -  HbA1c >= 7.0% and <= 9.0% at Screening.

          -  Currently treated with a basal-bolus insulin regimen (with or without metformin) for
             at least 3 months before Screening. The subject must be taking the following:

          -  Basal insulin (1 or 2 daily injections of neutral protamine Hagedorn insulin, insulin
             glargine, insulin detemir, or insulin degludec) AND

          -  Bolus insulin (at least 2 injections of regular insulin, insulin glulisine, insulin
             aspart, or insulin lispro) with a total daily dose of bolus insulin <= 70 units

          -  In addition, the total daily dose of insulin must be <= 140 units

          -  If taking metformin, a stable dose for at least 8 weeks before Screening Note: Subject
             should not have received any other antidiabetic medication within 30 days before
             screening (e.g., glucagon-like peptide-1 receptor (GLP-1R) agonist, dipeptidyl
             peptidase-IV inhibitor, SU, or thiazolidinedione). Subjects receiving commercially
             available premixed basal and prandial insulin are not eligible for this study.

          -  Fasting C-peptide >= 0.8 nanogram (ng) per milliliter (mL) [>= 0.26 nanomoles per
             litre (nmol/L)]

          -  Body mass index <= 40 kilogram per square meter( kg/m^2)

          -  Thyroid-stimulating hormone (TSH) level is normal or clinically euthyroid as
             demonstrated by further thyroid tests (e.g., free T4)

          -  Female subjects of childbearing potential (i.e., not surgically sterile and/or not
             postmenopausal) must be practicing adequate contraception (as defined in the protocol)
             for the duration of participation in the study including the 4-week post treatment
             Follow-up Period..

          -  Willing and able to comply with all study procedures including performance of frequent
             self-monitored blood glucose (SMBG) profiles according to the protocol

          -  Able and willing to provide written 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

          -  Current symptomatic biliary disease or history of acute or chronic pancreatitis

          -  Severe gastroparesis, i.e., requiring regular therapy within 6 months before Screening

          -  History of significant GI surgery that in the opinion of the investigator is likely to
             significantly affect upper GI or pancreatic function [e.g., gastric bypass and
             banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or
             surgeries thought to significantly affect upper GI function]

          -  History of severe hypoglycemia unawareness

          -  Diabetic complications (e.g., active proliferative retinopathy or severe diabetic
             neuropathy) or any other clinically significant abnormality (including a psychiatric
             disorder) that, in the opinion of the investigator, may pose additional risk in
             administering the investigational product

          -  Clinically significant CV and/or cerebrovascular disease within 3 months before
             Screening including, but not limited to, the following:

          -  Stroke or transient ischemic attack

          -  Acute coronary syndrome (myocardial infarction [MI] or unstable angina not responsive
             to nitroglycerin)

          -  Cardiac surgery or percutaneous coronary procedure

          -  Current or history of heart failure (New York Heart Association class III or IV)

          -  Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) or bilirubin >1.5 ×
             ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and
             direct bilirubin <35%)

          -  Unstable liver disease (as defined by the presence of ascites, encephalopathy,
             coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice),
             cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or
             asymptomatic gallstones). (Chronic stable hepatitis B and C are acceptable if subject
             otherwise meets entry criteria and is not on active antiviral treatment [e.g.,
             presence of hepatitis B surface antigen or positive hepatitis C test result within 3
             months of Screening])

          -  Hemoglobin <11 gram (g) per (dL) [<110 g/L] for male subjects and <10 g/dL (<100 g/L)
             for female subjects at Screening

          -  Estimated glomerular filtration rate (eGFR) <= 30 millilitre per minute per 1.73
             square meters (mL/min/1.73 m^2) (calculated using the Modification of Diet in Renal
             Disease [MDRD] formula) at Screening Note: As the use of metformin in subjects with
             varying degrees of renal function may differ from country to country, use of metformin
             should be in accordance with the metformin product label within the participating
             country.

          -  Fasting triglyceride level >750 mg/dL at Screening

          -  Hemoglobinopathy that may affect proper interpretation of HbA1c

          -  Known allergy to albiglutide or any product components (including yeast and human
             albumin), any other GLP-1 analogue, insulin, or other study medication's excipients OR
             other contraindications (per the prescribing information) for the use of potential
             study medications (e.g., insulin glargine, insulin lispro)

          -  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. However, short courses of oral steroids (single
             dose or multiple doses for up to 7 days) may be permitted provided these cases are
             discussed with the medical monitor. Inhaled, intra-articular, epidural, and topical
             corticosteroids are allowed

          -  Female subject is pregnant (confirmed by laboratory testing) or lactating

          -  Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is
             longer, before Screening, a history of receipt of an investigational antidiabetic drug
             within the 3 months before randomization, or receipt of albiglutide in previous
             studies