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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Safety and Efficacy of Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine Subjects With Type 2 Diabetes Mellitus

NCTNCT02229227 (opens ClinicalTrials.gov in a new tab)Other id200977Other id2014-001821-34Other id2014
Open at ClinicalTrials.govAsk about this trial

This trial does not test a peptide that PepBank tracks.

  • Measures Glucagon, does not give it. It appears in an outcome measure.

Overview

Status
Completed
Phase
Phase 3
Enrollment
814 participants (actual)
Sponsor
GlaxoSmithKline · Industry
Design
Randomized · Open label (no masking)
Countries
14 countries

United States, Brazil, Canada, France, Germany, Hungary, Italy, Mexico, Philippines, Poland, South Africa, South Korea, Spain, United Kingdom

Start
21 Nov 2014
Primary completion
24 Jul 2017
Completion
24 Jul 2017
First posted
1 Sept 2014 (estimated)
Last update posted
27 Nov 2020
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20142015201620172018
  1. Ph 3

    Safety and Efficacy of Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine Subjects With Type 2 Diabetes Mellitus

    NCT02229227

    21 Nov 2014 to 24 Jul 2017

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • AlbiglutideDrug
  • Insulin Glargine and Insulin LisproDrug

Arms2

  • Experimental

    Albiglutide + Insulin Glargine Arm

    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

  • Experimental

    Insulin Glargine + Insulin Lispro Arm

    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

Primary outcomes1

Outcomes the sponsor listed as primary.

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

    Time frame · Baseline (Day -1) and Week 26

    Registry description

    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.

Secondary outcomes(20)

  1. 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

    Time frame · Up to Week 26

    Registry description

    Participants who did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 were those participants treated with once-weekly albiglutide that were able to replace prandial insulin without lispro re-introduction through Week 26. 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 have been presented.

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

    Time frame · Up to Week 26

    Registry description

    Severe hypoglycemia was considered as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration \<=70 milligrams per deciliters (mg/dL) (\<=3.9 millimoles per liters \[mmol/L\]).

  3. Change From Baseline in Body Weight at Week 26

    Time frame · Baseline (Day -1) and Week 26

    Registry description

    Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. 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.

  4. Change From Baseline to Week 26 in Body Weight

    Time frame · Baseline (Day -1) to Week 26

    Registry description

    Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. 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. Change from Baseline to Week 26 in body weight are presented. FA Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

  5. Total Daily Insulin Dose at Week 26

    Time frame · Week 26

    Registry description

    Insulin dose at Week 26 was defined as the prescribed insulin dose at Week 25. Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 26 is presented. Only those participants available at the specified time points were analyzed.

  6. Change From Baseline to Week 26 in HbA1c

    Time frame · Baseline to Week 26

    Registry description

    HbA1c is glycosylated hemoglobin and was measured up to Week 26. 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. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

  7. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

    Time frame · Baseline and Week 26

    Registry description

    FPG was measured at Baseline (Day -1). FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the fasting serum glucose (FSG) values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. 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.

  8. Change From Baseline to Week 26 in FPG

    Time frame · Baseline to Week 26

    Registry description

    FPG was measured at Baseline (Day -1) up to Week 26. FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the FSG values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. 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.

  9. Number of Participants Achieving HbA1c <7.0% at Week 26

    Time frame · Week 26

    Registry description

    HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% at Week 26 are presented.

  10. Number of Participants Achieving HbA1c <7.0% up to Week 26

    Time frame · Up to Week 26

    Registry description

    HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% up to Week 26 are presented.

  11. Number of Participants Achieving a HbA1c <6.5% at Week 26

    Time frame · Week 26

    Registry description

    Number of participants achieving a HbA1c \<6.5% at Week 26 are presented.

  12. Number of Participants Achieving a HbA1c <6.5% up to Week 26

    Time frame · Up to Week 26

    Registry description

    Number of participants achieving a HbA1c \<6.5% up to Week 26 are presented.

  13. Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26

    Time frame · Week 26

    Registry description

    Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26 are presented.

  14. Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26

    Time frame · Up to Week 26

    Registry description

    Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26 are presented.

  15. Total Daily Insulin Dose at Week 4, Week 10 and Week 18

    Time frame · Weeks 4, 10, and 18

    Registry description

    Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 4, Week 10 and Week 18 is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

  16. Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits

    Time frame · Weeks 4, 10, 18, and 26

    Registry description

    Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

  17. Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits

    Time frame · Weeks 4, 10, 18, and 26

    Registry description

    Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

  18. Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26

    Time frame · Baseline (Day -1) and Weeks 4, 10, 18 and 26

    Registry description

    Total number of weekly insulin injections (7 days) to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26 are presented. Only those participants available at the specified time points were analyzed represented by n=X,X in category titles.

  19. Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26

    Time frame · Week 26

    Registry description

    Percentage of participants achieving HbA1c \<7.0% without weight gain are presented.

  20. Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26

    Time frame · Week 26

    Registry description

    Percentage of participants achieving HbA1c \<7.0% without severe or documented symptomatic hypoglycemia are presented.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline (Day -1) and Week 26

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

GroupValue (Percentage of glycosylated hemoglobin)Spread
Albiglutide + Insulin Glargine-1.040.041
Insulin Lispro + Insulin Glargine-1.100.040
Secondary and other outcome results(7)
Secondary outcomeNumber· Up to Week 26

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

GroupValue (Participants)
Albiglutide + Insulin Glargine218
Secondary outcomeNumber· Up to Week 26

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

GroupValue (Percentage of participants)
Albiglutide + Insulin Glargine57.2
Insulin Lispro + Insulin Glargine75.0
Secondary outcomeLeast squares mean· Baseline (Day -1) and Week 26

Change From Baseline in Body Weight at Week 26

GroupValue (Kilograms)Spread
Albiglutide + Insulin Glargine-1.950.207
Insulin Lispro + Insulin Glargine2.430.205
Secondary outcomeLeast squares mean· Baseline (Day -1) to Week 26

Change From Baseline to Week 26 in Body Weight

GroupValue (Kilograms)Spread
Albiglutide + Insulin Glargine-0.550.091
Insulin Lispro + Insulin Glargine0.660.091
Secondary outcomeLeast squares mean· Week 26

Total Daily Insulin Dose at Week 26

GroupValue (International Units)Spread
Albiglutide + Insulin Glargine70.362.160
Insulin Lispro + Insulin Glargine131.192.149
Secondary outcomeLeast squares mean· Baseline to Week 26

Change From Baseline to Week 26 in HbA1c

GroupValue (Percentage of glycosylated hemoglobin)Spread
Albiglutide + Insulin Glargine-0.590.023
Insulin Lispro + Insulin Glargine-0.470.023
Secondary outcomeLeast squares mean· Baseline and Week 26

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

GroupValue (Millimoles per Liter)Spread
Albiglutide + Insulin Glargine-2.010.120
Insulin Lispro + Insulin Glargine-1.460.121

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Albiglutide + Insulin GlargineDuring standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants received Albiglutide 30 mg weekly SC injection during the treatment period and insulin lispro dose was down-titrated to half that used in the standardization period. At Week 4, Albiglutide was up-titrated to 50 mg weekly SC injection and insulin lispro was stopped for the remainder of the treatment period.0 / 40023 / 400114 / 400
Insulin Lispro + Insulin GlargineDuring standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period.1 / 41331 / 413101 / 413

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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