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Safety and Efficacy Study of Albiglutide Liquid Drug Product in Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02683746
Recruitment Status : Completed
First Posted : February 17, 2016
Results First Posted : May 30, 2018
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

This is a phase III, randomized, double-blind, multicenter, parallel group, repeat-dose, study of 26 weeks duration to evaluate the efficacy, safety, tolerability and pharmacodynamic response of albiglutide liquid drug product relative to the commercial lyophilized drug product. The study will specifically evaluate the potential for immunogenicity (example [e.g.] incidences of anti-drug antibodies [ADA]) and injection site reactions (ISRs).

Albiglutide is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently long half-life to permit once a week injection. Currently, lyophilized albiglutide and the diluent are provided in a dual chamber cartridge (DCC), single-dose pen injector, requiring reconstitution prior to use. A liquid formulation of albiglutide will enable the commercialization of a liquid product in a single dose, ready-to-use prefilled syringe in an auto-injector.

The primary hypothesis of this study is to test that liquid drug product will provide glycemic control (as measured by HbA1c change from baseline) non-inferior to lyophilized drug product for a period of 26 weeks of treatment in subjects with T2DM.

This study will comprise of 3 study periods : screening (2 weeks), treatment (26 weeks) and for those subjects not entering the extension study a follow-up period (8 weeks). Approximately 300 subjects will be randomized in a 1:1 ratio to either Albiglutide active liquid auto-injector (LAI) plus Placebo lyophilized DCC pen injector (lyophilized DCC PI); or, Albiglutide lyophilized DCC PI plus Placebo LAI.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Lyophilized albiglutide DCC pen injector Drug: Lyophilized albiglutide DCC pen injector matching placebo Drug: Albiglutide liquid auto-injector Drug: Albiglutide liquid auto-injector matching placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Repeat-dose Study in Subjects With Type 2 Diabetes Mellitus to Assess the Efficacy, Safety, Tolerability and Pharmacodynamics, of Albiglutide Liquid Drug Product
Actual Study Start Date : March 16, 2016
Actual Primary Completion Date : April 3, 2017
Actual Study Completion Date : May 15, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Albiglutide

Arm Intervention/treatment
Experimental: Albiglutide active LAI plus Placebo lyophilized DCC PI
Subjects will receive 30 milligrams (mg) of albiglutide liquid drug product via auto injector and matching placebo via lyophilized DCC pen injector for 4 weeks. The dose will then be up-titrated to 50mg albiglutide for the remaining 22 weeks of the study. The study treatment will be administered once weekly by subcutaneous injection in the abdomen, thigh, or upper arm.
Drug: Lyophilized albiglutide DCC pen injector matching placebo
A fixed-dose, fully disposable pen injector system with a prefilled DCC containing matching placebo delivering an injection volume of 0.5mL

Drug: Albiglutide liquid auto-injector
A fixed-dose, single use, disposable auto-injector containing albiglutide liquid (30mg or 50mg) in a prefilled glass syringe. The auto-injector delivers the albiglutide liquid in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.

Experimental: Albiglutide lyophilized DCC PI plus Placebo LAI
Subjects will receive 30mg of albiglutide lyophilized drug product via DCC pen injector and matching placebo via auto injector for 4 weeks. The dose will then be up-titrated to 50mg albiglutide for the remaining 22 weeks of the study. The study treatment will be administered once weekly by subcutaneous injection in the abdomen, thigh, or upper arm.
Drug: Lyophilized albiglutide DCC pen injector
A fixed-dose, fully disposable pen injector system with a prefilled dual chamber glass cartridge (DCC) containing lyophilized albiglutide (30mg or 50mg) delivering an injection volume of 0.5mL.

Drug: Albiglutide liquid auto-injector matching placebo
A fixed-dose, single use, disposable auto-injector containing matching placebo in a prefilled glass syringe. The auto-injector delivers the matching placebo in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.




Primary Outcome Measures :
  1. Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 [ Time Frame: Baseline and Week 26 ]
    Blood samples will be collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a mixed-effect model with repeated measures (MMRM) method. The primary analysis will include all HbA1c values collected at scheduled visits from Week 4 up to Week 26. This will include values after hyperglycemia rescue and discontinuation from investigational product. Imputation under the non-inferiority null hypothesis for missing data will be incorporated.


Secondary Outcome Measures :
  1. Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Up to Week 26 ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function.

  2. Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) [ Time Frame: Up to Week 26 ]
    Chemistry parameters for which PCC values were identified were alanine aminotransferase (ALT) (if value >3 * upper limit of normal [ULN]), albumin (if value >5 gram/liter [g/L] above ULN or below lower limit of normal [LLN]), alkaline phosphatase (alk.phosph.) (if value >3*ULN), aspartate aminotransferase (AST) (if value >3*ULN), total bilirubin (if value >1.5 ULN), calcium (if value <1.8 or >3.0 millimoles per liter [mmol/L]), carbon di oxide (CO2) (if value <16 or >40 mmol/L), creatinine (if value >159 micromoles per liter [µmol/L]), direct bilirubin (if value >1.35*ULN), gamma glutamyl transferase (GGT) (if value >3*ULN), potassium (if value >0.5 mmol/L below LLN and >1.0 mmol/L above ULN), protein (if value >15 g/L above ULN or below LLN), sodium (>5 mmol/L below LLN or above ULN), urate (if value >654 µmol/L) and urea (if value >2*ULN). Number of participants with chemistry parameters of PCC at 'any visit post-Baseline' are presented.

  3. Number of Participants With Hematology Parameters of PCC [ Time Frame: Up to Week 26 ]
    Hematology parameters for which PCC values were identified were hematocrit (if value >0.05 below LLN or >0.04 above ULN), Hemoglobin (Hb) (if value >20 g/L below LLN or >10 g/L above ULN), lymphocytes (if value <0.5*LLN), neutrophils (if value <1 giga unit per liter [GI/L]) and platelets (if value <80 GI/L or >500 GI/L). Number of participants with hematology parameters of PCC at 'any visit post-Baseline' are presented.

  4. Number of Participants With Vital Signs of PCC [ Time Frame: Up to Week 34 ]
    Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a seated position after at least 5 minutes of rest. SBP values <100 millimeters of mercury (mmHg) and >170 mmHg, DBP values <50 mmHg and >110 mmHg, pulse rate values <50 beats per minute (bpm) and >120 bpm were considered as PCC values. Number of participants with PCC values of vital signs for 'any visit post-Baseline' are presented.

  5. Number of Participants With Electrocardiogram (ECG) Parameters of PCC [ Time Frame: Up to Week 26 ]
    Single measurements of 12-lead ECG were obtained in semi recumbent position using an ECG machine that automatically calculates the heart rate and measures PR and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Number of participants with ECG values of PCC at 'any visit post-Baseline' are presented. ECG mean heart rate values <50 or >120, PR interval >300 milliseconds (msec), QRS interval >200 msec, QTcF interval >=500 msec were considered as PCC values. Number of participants with PCC values of ECG parameters for 'any visit post-Baseline' are presented.

  6. Number of Participants With Positive Result for Anti-albiglutide Antibody [ Time Frame: Up to Week 34 ]
    Blood samples were obtained from participants at specific time points before administration of study treatment. The presence of anti-albiglutide antibodies was assessed using a validated enzyme linked immunosorbent assay (ELISA). The assay involves screening, confirmation, and titration steps (tiered-testing approach). Number of participants with positive anti- albiglutide antibody results at 'any visit post-Baseline' are presented.

  7. Number of Participants With Injection Site Reactions (ISR) [ Time Frame: Up to Week 34 ]
    Number of participants with ISR incidences were evaluated at specific time points. Each week included those participants with the onset of an ISR during that particular week as well as those participants with ISR from previous weeks that have not resolved.

  8. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [ Time Frame: Baseline and Week 26 ]
    Blood samples were collected from participants at specific time points to evaluate FPG to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model.

  9. Change From Baseline in HbA1c Over Time [ Time Frame: Baseline and up to Week 26 ]
    Blood samples were collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model and model-adjusted least square mean (LS mean) and standard error have been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

  10. Change From Baseline in FPG Over Time [ Time Frame: Baseline and up to Week 26 ]
    Blood samples were collected from participants at specific time points to evaluate FPG to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

  11. Trough Plasma Concentration of Albiglutide Over Time [ Time Frame: Pre-dose at Week 12 and Week 26 ]
    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of albiglutide. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 80 years of age inclusive
  • Historical diagnosis of type 2 diabetes mellitus (T2DM) (at least 3 months), experiencing inadequate glycemic control on current regimen of diet and exercise or on a stable maximal tolerated dose of metformin, maintained for approximately 8 weeks prior to screening.
  • HbA1c >=7.0 percent (%) and <=10%.
  • Hemoglobin >=11 grams per deciliter (g/dL) (>=110 grams per liter [g/L]) for males and >=10 g/dL (>=100 g/L) for females.
  • Body mass index <=40 kilograms per squared meter (kg/m^2)
  • Male or female
  • Able and willing to provide 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.
  • History of acute or chronic pancreatitis.
  • History of thyroid dysfunction or an abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at screening.
  • Severe gastroparesis, i.e., requiring regular therapy within 6 months before screening.
  • History of significant gastrointestinal (GI) surgery that in the opinion of the investigator is likely to significantly affect upper GI or pancreatic function
  • History of severe hypoglycemia unawareness
  • Diabetic complications or any other clinically significant abnormality .
  • Clinically significant Cardiovascular (CV) and/or cerebrovascular disease within 3 months before screening
  • QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 470 milliseconds (msec).
  • ALT >2.5x upper limit of the normal range (ULN) or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
  • Estimated glomerular filtration rate (eGFR) <=30 milliliter (mL)/minute (min)/1.73 squared meter (m^2) (calculated using the Modification of Diet in Renal Disease [MDRD] formula) at screening.
  • Fasting triglyceride level >750 milligrams per deciliter (mg/dL) at screening.
  • Hemoglobinopathy that may affect proper interpretation of HbA1c.
  • Medical or psychiatric disorders that would preclude effective participation in study.
  • 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.
  • Use of dipeptidyl peptidase-IV inhibitors within the 3 months before randomization.
  • History of alcohol or substance abuse within one year before screening.
  • Known allergy to albiglutide or any product components (including yeast and human albumin), any other glucagon-like peptide-1 (GLP-1) analogue, or other study medication's excipients OR other contraindications (per the prescribing information) for the use of potential study medications.
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02683746


Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] May 26, 2016
Statistical Analysis Plan  [PDF] July 14, 2017

Publications:
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02683746    
Other Study ID Numbers: 200952
First Posted: February 17, 2016    Key Record Dates
Results First Posted: May 30, 2018
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
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.
URL: https://www.clinicalstudydatarequest.com/SearchAllPostings.aspx?searchparam=200952
Keywords provided by GlaxoSmithKline:
Pharmacodynamics
Safety
Albiglutide
Tolerability
Type 2 Diabetes Mellitus
Efficacy
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
rGLP-1 protein
Glucagon-Like Peptide 1
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs