A Study to Determine the Safety and Efficacy of Albiglutide Administered in Combination With Insulin Glargine

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Randomized, Open-Label, Active-Controlled, Parallel-Group, Multicenter Study to Determine the Safety and Efficacy of Albiglutide Administered in Combination With Insulin Glargine as Compared With the Combination of Insulin Glargine and Preprandial Lispro Insulin in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976391
• Other study ID #: 108486
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2009
• Last updated: July 31, 2014
• Start date: September 2009
• Est. completion date: October 2011

Study information

• Verified date: June 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

This randomized, open-label, active-controlled, parallel-group, multicenter study evaluates the safety and efficacy of a weekly subcutaneously injected dose 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. Subjects with a historical diagnosis of type 2 diabetes who are inadequately controlled despite the use of insulin glargine or other intermediate- or long-acting insulins for >/= 6 months but < 5 years, with or without oral antidiabetic medications, who are unable to achieve a glycosylated hemoglobin value of < 7% will be recruited into the study. Subjects must also be willing and capable of pursuing an intensive regimen of both basal and preprandial insulin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 586
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Biological:
• albiglutide + insulin glargine
albiglutide in combination with insulin glargine

Drug:
• insulin glargine + preprandial lispro insulin
insulin glargine in combination with preprandial lispro insulin

Locations

Country	Name	City	State
Brazil	GSK Investigational Site	Brasília
Brazil	GSK Investigational Site	Mogi das Cruzes
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
France	GSK Investigational Site	Armentières
France	GSK Investigational Site	Venissieux
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Hong Kong	GSK Investigational Site	Shatin
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Manipal
Korea, Republic of	GSK Investigational Site	Goyang-si
Korea, Republic of	GSK Investigational Site	Koyang-shi
Korea, Republic of	GSK Investigational Site	Seongnam-si
Korea, Republic of	GSK Investigational Site	Seongnam-si,
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon, Kyonggi-do
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Pachuca	Hidalgo
Mexico	GSK Investigational Site	Puebla
Peru	GSK Investigational Site	Huacho	Lima
Peru	GSK Investigational Site	Ica
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Piura
Peru	GSK Investigational Site	Trujillo
Philippines	GSK Investigational Site	Marikina City
Philippines	GSK Investigational Site	Pasay
Philippines	GSK Investigational Site	Pasig
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	San Juan
Philippines	GSK Investigational Site	Tagbilaran City
Philippines	GSK Investigational Site	Taytay Rizal
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Boksburg North	Gauteng
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Durban	KwaZulu- Natal
South Africa	GSK Investigational Site	Durban	KwaZulu- Natal
South Africa	GSK Investigational Site	Johannesburg	Gauteng
South Africa	GSK Investigational Site	Johannesburg	Gauteng
South Africa	GSK Investigational Site	Johannesburg	Gauteng
South Africa	GSK Investigational Site	Kempton Park
South Africa	GSK Investigational Site	Lenasia	Gauteng
South Africa	GSK Investigational Site	Parow
South Africa	GSK Investigational Site	Port Elizabeth	Eastern Cape
South Africa	GSK Investigational Site	Pretoria	Gauteng
South Africa	GSK Investigational Site	Somerset West
Spain	GSK Investigational Site	Alzira
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Sabadell
Spain	GSK Investigational Site	Sevilla
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei County
United Kingdom	GSK Investigational Site	Hull
United Kingdom	GSK Investigational Site	Liverpool	Merseyside
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Plymouth
United States	GSK Investigational Site	Akron	Ohio
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Arlington	Texas
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Avon	Indiana
United States	GSK Investigational Site	Bedford	Texas
United States	GSK Investigational Site	Bensalem	Pennsylvania
United States	GSK Investigational Site	Benzonia	Michigan
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Bloomfield Hills	Michigan
United States	GSK Investigational Site	Blue Ridge	Georgia
United States	GSK Investigational Site	Bountiful	Utah
United States	GSK Investigational Site	Boynton Beach	Florida
United States	GSK Investigational Site	Burke	Virginia
United States	GSK Investigational Site	Burlington	North Carolina
United States	GSK Investigational Site	Canal Fulton	Ohio
United States	GSK Investigational Site	Carlisle	Pennsylvania
United States	GSK Investigational Site	Chesterfield	Missouri
United States	GSK Investigational Site	Chino	California
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Clarksville	Tennessee
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Commerce	California
United States	GSK Investigational Site	Corpus Christi	Texas
United States	GSK Investigational Site	Council Bluffs	Iowa
United States	GSK Investigational Site	Cutler Bay	Florida
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Dearborn	Michigan
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Des Moines	Iowa
United States	GSK Investigational Site	Dothan	Alabama
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Evansville	Indiana
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Fullerton	California
United States	GSK Investigational Site	Gilbert	Arizona
United States	GSK Investigational Site	Great Falls	Montana
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Haddon Heights	New Jersey
United States	GSK Investigational Site	Hallandale Beach	Florida
United States	GSK Investigational Site	Hampton	Virginia
United States	GSK Investigational Site	Haverhill	Massachusetts
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Honolulu	Hawaii
United States	GSK Investigational Site	Honolulu	Hawaii
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Hyattsville	Maryland
United States	GSK Investigational Site	Idaho Falls	Idaho
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jefferson City	Missouri
United States	GSK Investigational Site	Johnson City	Tennessee
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Kalamazoo	Michigan
United States	GSK Investigational Site	Kalamazoo	Michigan
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Katy	Texas
United States	GSK Investigational Site	La Grange	Illinois
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Lafayette	Indiana
United States	GSK Investigational Site	LaJolla	California
United States	GSK Investigational Site	Lake Jackson	Texas
United States	GSK Investigational Site	Lauderdale Lakes	Florida
United States	GSK Investigational Site	Lewisburg	West Virginia
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Alamitos	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Manassas	Virginia
United States	GSK Investigational Site	McKenzie	Tennessee
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Midland	Texas
United States	GSK Investigational Site	Mission Viejo	California
United States	GSK Investigational Site	Morehead City	North Carolina
United States	GSK Investigational Site	Murrells Inlet	South Carolina
United States	GSK Investigational Site	New Britain	Connecticut
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newton	Kansas
United States	GSK Investigational Site	North Massapequa	New York
United States	GSK Investigational Site	North Richland Hills	Texas
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Picayune	Mississippi
United States	GSK Investigational Site	Plantation	Florida
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Satna Monica	California
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Schertz	Texas
United States	GSK Investigational Site	Searcy	Arkansas
United States	GSK Investigational Site	Shreveport	Louisiana
United States	GSK Investigational Site	Snellville	Georgia
United States	GSK Investigational Site	South Burlington	Vermont
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Spring Valley	California
United States	GSK Investigational Site	Springfield	Missouri
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Sugar Land	Texas
United States	GSK Investigational Site	Tabor City	North Carolina
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Tipton	Pennsylvania
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Trumbull	Connecticut
United States	GSK Investigational Site	Tullahoma	Tennessee
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Tustin	California
United States	GSK Investigational Site	Uniontown	Pennsylvania
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	Waterbury	Connecticut
United States	GSK Investigational Site	West Hills	California
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Brazil,  France,  Germany,  Hong Kong,  India,  Korea, Republic of,  Mexico,  Peru,  Philippines,  South Africa,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 26	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The BL HbA1c value is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 26 minus the value at BL. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (<65 years versus =65 years) as factors and Baseline HbA1c as a continuous covariate.The last observation carried forward (LOCF) method was used to impute missing post-BL HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values.	Baseline and Week 26	No
Secondary	Change From Baseline in HbA1c at Weeks 36, 48 and 52	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline is defined as the last available assessment on or prior to the first dose of study drug. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.	Baseline and Weeks 36, 48 and 52	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline FPG + Baseline HbA1c category + region	Baseline and Week 26	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 36, 48 and 52	The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline FPG minus the Baseline FPG. This analysis used observed FPG values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.	Baseline and Weeks 36, 48 and 52	No
Secondary	Number of Participants Who Achieved HbA1c Response Level of <6.5% and <7.0% at Week 26	The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5% and <7.0% at Week 26) were assessed.	Week 26	No
Secondary	Time to Hyperglycemia Rescue	Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: HbA1c >9.0% and <0.5% decrease from Baseline between >=Week 4 and	From the start of study medication until the end of the treatment (up to Week 52)	No
Secondary	Change From Baseline in Body Weight at Week 26	The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region + current oral antidiabetic therapy.	Baseline and Week 26	No
Secondary	Change From Baseline in Body Weight at Weeks 36, 48 and 52	The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.	Baseline and Weeks 36, 48 and 52	No