Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine in the Treatment of patients With Type 2 Diabetes Mellitus: The Switch Study

Phase 1

• Conditions: Diabetes mellitus type 2; MedDRA version: 18.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-001821-34-GB
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-11-26
• Study Completion: 2017-07-24
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 814

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Male or female, 18 to 75 years of age (inclusive at the time of Screening) with T2DM
2. HbA1c =7.0% and =9.5% at Screening. If the first screening HbA1c does not meet the eligibility criterion, the HbA1c value may be checked up to 2 times during Screening, and if the average of these determinations meets the criterion, the subject may be eligible for further participation in the study.
3. 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., GLP-1R agonist, dipeptidyl peptidase-IV inhibitor, SU, meglitinide, sodium-glucose transporter 2 inhibitor or thiazolidinedione). Subjects receiving commercially available premixed basal and prandial insulin are not eligible for this study.
4. Fasting C-peptide =0.8 ng/mL (=0.26 nmol/L). If the fasting C-peptide is <0.8 ng/mL (<0.26 nmol/L) but stimulated C-peptide 90 minutes after a standardized mixed meal is =1.5 ng/mL (=0.5 nmol/L), the subject may be eligible for further participation in the study [Jones, 2013; Maldonado, 2005]. Note: Plasma glucose will also be measured 90 minutes after the standardized mixed meal; if the concurrent plasma glucose collected 90 minutes
after the standardized mixed meal is not =144.0 mg/dL (?=8.0mmol/L), the stimulated C-peptide test may be repeated during an unscheduled visit.
5. Body mass index =40 kg/m2
6. Thyroid-stimulating hormone (TSH) level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., free T4)
7. Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (as defined below) for the duration of participation in the study including the 4-week Posttreatment Follow-up Period
•Abstinence from penile-vaginal intercourse, when this is the female’s preferred and usual lifestyle
•Oral contraceptive, either combined or progestogen alone
•Injectable progestogen
•Implants of etonogestrel or levonorgestrel
•Estrogenic vaginal ring
•Percutaneous contraceptive patches
•Intrauterine device or intrauterine system that has a failure rate of less than 1% per year when used consistently and correctly as stated in the product label
•Male partner sterilization prior to the female subject’s entry into the study, and this male is the sole partner for that subject. The information on the male sterility can come from the si

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. Type 1 diabetes mellitus
2. 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)
3. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
4. Current symptomatic biliary disease or history of acute or chronic pancreatitis
5. Severe gastroparesis, i.e., requiring regular therapy within 6 months before Screening
6. 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)
7. History of hypoglycemia unawareness (i.e., the absence of autonomic warning symptoms before the development of neuroglycopenic symptoms such as blurred vision, difficulty speaking, feeling faint, difficulty thinking, and confusion)
8. 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
9. 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)
10.Any history of (New York Heart Association class III or IV) heart failure.
11. 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%)

12. 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])

13. Hemoglobin <11 g/dL (<110 g/L) for male subjects and <10 g/dL (<100 g/L) for female subjects at Screening

14. Estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m2 (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, us

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified