NCT02229227

Brief 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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
814

participants targeted

Target at P75+ for phase_3 diabetes-mellitus-type-2

Timeline
Completed

Started Nov 2014

Longer than P75 for phase_3 diabetes-mellitus-type-2

Geographic Reach
14 countries

157 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 28, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 1, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

November 21, 2014

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 24, 2017

Completed
11 months until next milestone

Results Posted

Study results publicly available

June 29, 2018

Completed
Last Updated

November 27, 2020

Status Verified

November 1, 2020

Enrollment Period

2.7 years

First QC Date

August 28, 2014

Results QC Date

June 1, 2018

Last Update Submit

November 13, 2020

Conditions

Keywords

switch studyalbiglutideglucagon-like peptide-1 receptor agonistType 2 diabetes mellitusbasal-bolus insulin therapy

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26

    HbA1c is glycosylated hemoglobin. It was measured at Baseline and at Week 26. The analysis was conducted using mixed-effect model with repeated measures (MMRM). The model included HbA1c change from Baseline as the dependent variable; treatment, region, age category, current metformin use, visit week, treatment-by-week interaction, and Baseline HbA1c-by-week interaction as fixed effects; Baseline HbA1c as a continuous covariate; and participant as a random effect. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.

    Baseline (Day -1) and Week 26

Secondary Outcomes (39)

  • Number of Participants Treated With Once-weekly Albiglutide That Were Able to Discontinue Insulin Lispro at Week 4 and Did Not Meet Prespecified Criteria for Severe, Persistent Hyperglycemia Through Week 26

    Up to Week 26

  • Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26

    Up to Week 26

  • Change From Baseline in Body Weight at Week 26

    Baseline (Day -1) and Week 26

  • Change From Baseline to Week 26 in Body Weight

    Baseline (Day -1) to Week 26

  • Total Daily Insulin Dose at Week 26

    Week 26

  • +34 more secondary outcomes

Study Arms (2)

Albiglutide + Insulin Glargine Arm

EXPERIMENTAL

During standardization period, subjects will transit from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. During treatment period, subject will receive Albiglutide 30 milligrams (mg) weekly subcutaneous (SC) injection and insulin lispro dose will be downtitrated to half that used in the standardization period. At Week 4, Albiglutide will be uptitrated to 50 mg weekly SC injection and insulin lispro will be stopped for the remainder of the treatment Period. Insulin lispro may be re-introduced after Week 8 according to pre-defined hyperglycemia thresholds. Insulin will be adjusted according to protocol-defined insulin titration algorithms

Drug: Albiglutide

Insulin Glargine + Insulin Lispro Arm

EXPERIMENTAL

During standardization period, subjects will transit from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. During treatment period, subject will continue with the same doses as at the end of the standardization period and doses will be adjusted according to protocol-defined insulin titration algorithms

Drug: Insulin Glargine and Insulin Lispro

Interventions

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

Albiglutide + Insulin Glargine Arm

Insulin glargine and insulin lispro will be provided as injection pens for SC injection

Insulin Glargine + Insulin Lispro Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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 \[e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of Screening\])
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (157)

GSK Investigational Site

Searcy, Arkansas, 72143, United States

Location

GSK Investigational Site

Huntington Beach, California, 92648, United States

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GSK Investigational Site

Long Beach, California, 90807, United States

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GSK Investigational Site

Los Angeles, California, 90017, United States

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GSK Investigational Site

Tustin, California, 92780, United States

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GSK Investigational Site

West Hills, California, 91307, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80909, United States

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GSK Investigational Site

Brooksville, Florida, 34601, United States

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GSK Investigational Site

Clearwater, Florida, 33765, United States

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GSK Investigational Site

Hialeah, Florida, 33012, United States

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GSK Investigational Site

Miami, Florida, 33156, United States

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GSK Investigational Site

Orlando, Florida, 32825, United States

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GSK Investigational Site

Pembroke Pines, Florida, 33027, United States

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GSK Investigational Site

Tampa, Florida, 33634, United States

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GSK Investigational Site

West Palm Beach, Florida, 33401, United States

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GSK Investigational Site

Chicago, Illinois, 60612, United States

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GSK Investigational Site

Paducah, Kentucky, 42003, United States

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GSK Investigational Site

Lake Charles, Louisiana, 70601, United States

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GSK Investigational Site

Shreveport, Louisiana, 71105, United States

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GSK Investigational Site

Kalamazoo, Michigan, 49009, United States

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GSK Investigational Site

Springfield, Missouri, 65807, United States

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GSK Investigational Site

Las Vegas, Nevada, 89119, United States

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GSK Investigational Site

Staten Island, New York, 10301, United States

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GSK Investigational Site

Shelby, North Carolina, 28150, United States

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GSK Investigational Site

Wilmington, North Carolina, 28401, United States

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GSK Investigational Site

Columbus, Ohio, 43213, United States

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GSK Investigational Site

Dayton, Ohio, 45439, United States

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GSK Investigational Site

Kettering, Ohio, 45429, United States

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GSK Investigational Site

Austin, Texas, 78749, United States

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GSK Investigational Site

Austin, Texas, 78756, United States

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GSK Investigational Site

Dallas, Texas, 75230, United States

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GSK Investigational Site

Houston, Texas, 77058, United States

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GSK Investigational Site

Houston, Texas, 77099, United States

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GSK Investigational Site

Pharr, Texas, 78577, United States

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GSK Investigational Site

Round Rock, Texas, 78681, United States

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GSK Investigational Site

Sugar Land, Texas, 77479, United States

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GSK Investigational Site

Hampton, Virginia, 23666, United States

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GSK Investigational Site

Renton, Washington, 98057, United States

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GSK Investigational Site

Tacoma, Washington, 98405, United States

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GSK Investigational Site

Fortaleza, Ceará, 60115-282, Brazil

Location

GSK Investigational Site

Fortaleza - CE, Ceará, 60430-350, Brazil

Location

GSK Investigational Site

Goiânia, Goiás, 74110-010, Brazil

Location

GSK Investigational Site

Uberlândia, Minas Gerais, 38411-186, Brazil

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GSK Investigational Site

Porto Alegre, Rio Grande do Sul, 90035-170, Brazil

Location

GSK Investigational Site

Porto Alegre, Rio Grande do Sul, 90035001, Brazil

Location

GSK Investigational Site

Campinas, São Paulo, 13010-001, Brazil

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GSK Investigational Site

Marília, São Paulo, 17519-000, Brazil

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GSK Investigational Site

Pará, 66073-000, Brazil

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GSK Investigational Site

São Paulo, 01223-001, Brazil

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GSK Investigational Site

São Paulo, 04038-002, Brazil

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GSK Investigational Site

Penticton, British Columbia, V2A 5C8, Canada

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GSK Investigational Site

Brampton, Ontario, L6S 0C9, Canada

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GSK Investigational Site

Oakville, Ontario, L6M 1M1, Canada

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GSK Investigational Site

Thornhill, Ontario, L4J 8L7, Canada

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GSK Investigational Site

Toronto, Ontario, M4G 3E8, Canada

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GSK Investigational Site

Saint-Laurent, Quebec, H4T 1Z9, Canada

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GSK Investigational Site

Corbeil-Essonnes, 91106, France

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GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Valenciennes, 59322, France

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GSK Investigational Site

Vandœuvre-lès-Nancy, 54501, France

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GSK Investigational Site

Vénissieux, 69200, France

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GSK Investigational Site

Bad Mergentheim, Baden-Wurttemberg, 97980, Germany

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GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69115, Germany

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GSK Investigational Site

Wangen, Baden-Wurttemberg, 88239, Germany

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GSK Investigational Site

Aschaffenburg, Bavaria, 63739, Germany

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GSK Investigational Site

Sulzbach-Rosenberg, Bavaria, 92237, Germany

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GSK Investigational Site

Aßlar, Hesse, 35614, Germany

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GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19059, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45355, Germany

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GSK Investigational Site

Ludwigshafen am Rhein, Rhineland-Palatinate, 67059, Germany

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GSK Investigational Site

Rhaunen, Rhineland-Palatinate, 55624, Germany

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GSK Investigational Site

Saarlouis, Saarland, 66740, Germany

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GSK Investigational Site

Sankt Ingbert, Saarland, 66386, Germany

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GSK Investigational Site

Dresden, Saxony, 01307, Germany

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GSK Investigational Site

Pirna, Saxony, 01796, Germany

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GSK Investigational Site

Berlin, 10115, Germany

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GSK Investigational Site

Baja, 6500, Hungary

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GSK Investigational Site

Balatonfüred, 8230, Hungary

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GSK Investigational Site

Budaörs, 2040, Hungary

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GSK Investigational Site

Budapest, 1036, Hungary

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GSK Investigational Site

Budapest, 1158, Hungary

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GSK Investigational Site

Debrecen, 4031, Hungary

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GSK Investigational Site

Pécs, 7643, Hungary

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GSK Investigational Site

Zalaegerszeg, 8900, Hungary

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GSK Investigational Site

Napoli, Campania, 80131, Italy

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GSK Investigational Site

Bologna, Emilia-Romagna, 40138, Italy

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GSK Investigational Site

Rome, Lazio, 00128, Italy

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GSK Investigational Site

Milan, Lombardy, 20122, Italy

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GSK Investigational Site

Milan, Lombardy, 20132, Italy

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GSK Investigational Site

Pavia, Lombardy, 27100, Italy

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GSK Investigational Site

Pachuca, Hidalgo, 42084, Mexico

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GSK Investigational Site

Guadalajara, Jalisco, 44570, Mexico

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GSK Investigational Site

Guadalajara, Jalisco, 44657, Mexico

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GSK Investigational Site

Guadalajara, Jalisco, 44670, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64020, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64460, Mexico

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GSK Investigational Site

Monterrey NL, Nuevo León, 64718, Mexico

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GSK Investigational Site

Mérida, Yucatán, 97070, Mexico

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GSK Investigational Site

Aguascalientes, 20129, Mexico

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GSK Investigational Site

Aguascalientes, 20230, Mexico

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GSK Investigational Site

Chihuahua City, 31217, Mexico

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GSK Investigational Site

Durango, 34000, Mexico

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GSK Investigational Site

Durango, 34080, Mexico

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GSK Investigational Site

Guadalajara, 44600, Mexico

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GSK Investigational Site

Mexico City, 03300, Mexico

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GSK Investigational Site

México, 07760, Mexico

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GSK Investigational Site

México, 14000, Mexico

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GSK Investigational Site

Veracruz, 91020, Mexico

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GSK Investigational Site

Davao City, 8000, Philippines

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GSK Investigational Site

Manila, 1000, Philippines

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GSK Investigational Site

Marikina City, 1810, Philippines

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GSK Investigational Site

Quezon City, 2000, Philippines

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GSK Investigational Site

Bialystok, 15-435, Poland

Location

GSK Investigational Site

Kamieniec Ząbkowicki, 57-230, Poland

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GSK Investigational Site

Lodz, 90-132, Poland

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GSK Investigational Site

Oświęcim, 32-600, Poland

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GSK Investigational Site

Puławy, 24-100, Poland

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GSK Investigational Site

Radom, 26-610, Poland

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GSK Investigational Site

Ruda Śląska, 41-709, Poland

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GSK Investigational Site

Zamość, 22-400, Poland

Location

GSK Investigational Site

Bloemfontein, Free State, 9301, South Africa

Location

GSK Investigational Site

Johannesburg, Gauteng, 1685, South Africa

Location

GSK Investigational Site

Johannesburg, Gauteng, 2013, South Africa

Location

GSK Investigational Site

Durban, KwaZulu-Natal, 4067, South Africa

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GSK Investigational Site

Johannesburg, 2193, South Africa

Location

GSK Investigational Site

Krugersdorp, 1724, South Africa

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GSK Investigational Site

Worcester, 6850, South Africa

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GSK Investigational Site

Gyeonggido, 420-717, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

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GSK Investigational Site

A Coruña, 15006, Spain

Location

GSK Investigational Site

Alcalá de Henares, 28805, Spain

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GSK Investigational Site

Alzira/Valencia, 46600, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barakaldo (Vizcaya), 48903, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Barcelona, 8041, Spain

Location

GSK Investigational Site

Ferrol. La Coruña, 15405, Spain

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GSK Investigational Site

Granada, 18012, Spain

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GSK Investigational Site

Granada, 18014, Spain

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GSK Investigational Site

León, 24071, Spain

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GSK Investigational Site

Lleida, 25198, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Majadahonda, 28220, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Mérida, 6800, Spain

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GSK Investigational Site

Palma de Mallorca, 07120, Spain

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GSK Investigational Site

Palma de Mallorca, 07198, Spain

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GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Valencia, 46014, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Welwyn Garden City, Hertfordshire, AL7 4HQ, United Kingdom

Location

GSK Investigational Site

Bath, Somerset, BA1 3NG, United Kingdom

Location

GSK Investigational Site

Hull, HU3 2JZ, United Kingdom

Location

GSK Investigational Site

Lancashire, BL9 7TD, United Kingdom

Location

GSK Investigational Site

Sidcup, DA14 6LT, United Kingdom

Location

Related Publications (1)

  • Rosenstock J, Nino A, Soffer J, Erskine L, Acusta A, Dole J, Carr MC, Mallory J, Home P. Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, on Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial. Diabetes Care. 2020 Oct;43(10):2509-2518. doi: 10.2337/dc19-2316. Epub 2020 Jul 21.

    PMID: 32694215BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rGLP-1 proteinInsulin GlargineInsulin Lispro

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-ActingInsulinsPancreatic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPeptidesAmino Acids, Peptides, and ProteinsInsulin, Short-Acting

Results Point of Contact

Title
GSK Response Center
Organization
GlaxoSmithKline

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 28, 2014

First Posted

September 1, 2014

Study Start

November 21, 2014

Primary Completion

July 24, 2017

Study Completion

July 24, 2017

Last Updated

November 27, 2020

Results First Posted

June 29, 2018

Record last verified: 2020-11

Data Sharing

IPD Sharing
Will share

IPD for this study is available via the Clinical Study Data Request site.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
More information

Locations