A Study to Determine the Safety and Efficacy of Albiglutide Administered in Combination With Insulin Glargine
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: albiglutide + insulin glargine; insulin glargine + preprandial lispro insulin
Intervention description: albiglutide in combination with insulin glargine; insulin glargine in combination with preprandial lispro insulin
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; 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: 586.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: open-label; albiglutide; insulin glargine; preprandial insulin

Summary:

      This study will examine the safety and efficacy of albiglutide in combination with insulin
      glargine as compared with the combination of insulin glargine and preprandial lispro insulin
      in subjects with type 2 diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with type 2 diabetes, currently treated with insulin glargine or other
             intermediate- or long-acting insulin, with or without oral antidiabetic medications,
             but experiencing inadequate glycemic control and willing and capable of participating
             in a regimen of intensive insulin administration. A subject who has been on an
             intermediate- or long acting insulin for >/=6 months but <5 years, and, in spite of
             dosage adjustments based on home blood glucose monitoring, is unable to achieve a
             HbA1c of <7%.

          -  BMI >/= 20kg/m2 and </=45 kg/m2

          -  Fasting C-peptide >/=0.8 ng/mL (>/= 0.26 nmol/L)

          -  HbA1c between 7.0% and 10.5%, inclusive

          -  Use of oral or systemically injected glucocorticoids is generally not allowed within 3
             months before randomization; inhaled, intra articular, and topical corticosteroids are
             allowed

          -  Hemoglobin </=11 g/dL for male subjects and >/=10 g/dL for female subjects

          -  Creatinine clearance >60 mL/min (calculated using the Cockcroft Gault formula)

          -  Thyroid stimulating hormone level is normal or clinically euthyroid as demonstrated by
             further thyroid tests (e.g., T4, T3, thyroid-binding globulin)

          -  Female subjects of childbearing potential (i.e., not surgically sterile and/or not
             postmenopausal) must be practicing adequate contraception. Adequate contraception must
             be practiced for the duration of participation in the study including the 8 week
             Posttreatment Follow-up Period

          -  Able and willing to monitor his or her own blood glucose concentrations with a home
             glucose monitor as per the protocol recommendations of self administration

          -  No major illness or debility that in the investigator's opinion prohibits the subject
             from actively participating in their diabetes management and completing the study

          -  Able and willing to provide written informed consent

        Exclusion Criteria:

          -  History of cancer, other than squamous cell or basal cell carcinoma of the skin, that
             has not been in full remission for at least 3 years before Screening.

          -  History of treated diabetic gastroparesis

          -  Current ongoing symptomatic biliary disease or history of pancreatitis

          -  History of significant gastrointestinal surgery, including gastric bypass and banding,
             antrectomy, Roux en Y bypass, gastric vagotomy, small bowel resection, or surgeries
             thought to significantly affect upper gastrointestinal function

          -  Recent clinically significant cardiovascular and/or cerebrovascular disease including
             but not limited to the following:

               -  Previous history of stroke or transient ischemic attack within 1 month before
                  Screening.

               -  Acute coronary syndrome, which includes the following:

               -  Documented MI within the 2 months before Screening and during the period up until
                  receiving the first dose of study medication

               -  Any cardiac surgery including percutaneous transluminal coronary angioplasty,
                  coronary stent placement, or coronary artery bypass graft surgery within the 2
                  months before Screening and during the period up until receiving the first dose
                  of study medication

               -  Unstable angina not responsive to nitroglycerin within the 2 months before
                  Screening and during the period up until receiving the first dose of study
                  medication

               -  Unstable cardiac rhythm, however, as an example, controlled atrial fibrillation
                  is allowed

               -  Current or history of heart failure (New York Heart Association class I to IV).

               -  Resting systolic pressure is >160 mm Hg and/or diastolic pressure >100 mm Hg.

               -  QTc interval (Fridericia) >470 ms confirmed by a central reader at Screening

          -  History of stroke or other central nervous system disorder that would negatively
             impact the subject's ability to participate in a program of intensive insulin
             management (eg, physically or mentally incapable of performing home blood glucose
             monitoring or administering and/or adjusting insulin dosage)

          -  Hemoglobinopathy that may affect determination of HbA1c

          -  History of human immunodeficiency virus infection

          -  History of total bilirubin >1.5 × ULN unless the subject has a previously known
             history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated
             bilirubin <35% of total bilirubin

          -  ALT or aspartate aminotransferase (AST) >2.5 ×ULN

          -  Fasting triglyceride level >850 mg/dL at Screening or Week -1 (Visit 5).

          -  Acute symptomatic (within 3 months before Screening) infection with hepatitis B or
             hepatitis C; however, subjects with past or chronic hepatitis B or hepatitis C are
             allowed provided the requirements for ALT, AST, and total bilirubin are met

          -  History of a psychiatric disorder that will affect the subject's ability to
             participate in the study

          -  History of alcohol or substance abuse within 1 year before Screening

          -  Positive urine drug screen at Screening, unless the subject is taking a medically
             approved medication for which a positive drug screen simply verifies the use of this
             medication

          -  Hypoglycemia unawareness which has impaired cognitive function and required outside
             assistance

          -  Female subject is pregnant (confirmed by laboratory testing), lactating, or <6 weeks
             postpartum

          -  Known allergy to any GLP 1 analogue, insulin, other study medications' excipients,
             excipients of albiglutide, or Baker's yeast

          -  Receipt of any investigational drug within the 30 days, or 5 half lives whichever is
             longer, before Screening or a history of receipt of an investigational antidiabetic
             drug within the 3 months before randomization, or receipt of albiglutide in previous
             studies

          -  Current use of any GLP 1 analogue

          -  History of type 1 diabetes mellitus, diabetic complications (e.g., active
             proliferative retinopathy or severe diabetic neuropathy) that in the opinion of the
             investigator would preclude effective participation in the study, or a history of
             ketoacidosis or hyperosmolar coma

          -  Contraindications (as per the prescribing information) for the use of either
             background or potential randomized study medications (e.g., insulin glargine or lispro
             insulin)

          -  History or family history of medullary carcinoma

          -  History or family history of multiple endocrine neoplasia type 2