Back to resultsBioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Albiglutide Liquid Auto-injector
Albiglutide Lyophilized DCC Pen Injector
Placebo Liquid Auto-injector
Placebo Lyophilized DCC Pen injector
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Albiglutide, Randomized, Pharmacokinetics, GSK716155, Bioequivalence study
Eligibility Criteria
Inclusion Criteria:
- Between 18 and 65 years of age.
- Healthy.
- Subject is a nonsmoker.
- Subject's body mass index (BMI) is >=18 kilogram/meter square (kg/m^2) and <=30 kg/m^2
- Male or
- Female
Exclusion Criteria:
- Alanine aminotransferase (ALT) >1.5 x upper limit of normal range (ULN)
- Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
- QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 millisecond (msec).
- Systolic blood pressure is >=140 millimeter of mercury (mmHg) at Screening;
- Diastolic blood pressure is >=90 mmHg at Screening;
- Heart rate is >100 beats/min at Screening.
- estimated glomerular filtration rate (eGFR) <=80 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) at Screening.
- Fasting triglyceride level >300 milligram per deciliter (mg/dL) at Screening.
- History of significant cardiovascular or pulmonary dysfunction prior to Screening.
- History of thyroid dysfunction or an abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at Screening.
- History of gastrointestinal surgery that could influence gastric emptying (e.g., gastrectomy, gastric bypass).
- History of pancreatitis.
- Personal or family history of multiple endocrine neoplasia type 2.
- Personal or family history of medullary carcinoma of the thyroid.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days.
- History of regular alcohol consumption within 6 months of the study.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
- Subject has previously received any GLP-1 mimetic compound (eg., exenatide, liraglutide, lixisenatide, dulaglutide).
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
- Subject has donated blood in excess of 500 mL within 56 days prior to dosing or intention of donating in the month after completing the study.
- 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).
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Regimen AB
Regimen BA
Arm Description
Subjects will be receive Regimen A treatment in Session 1 followed by Regimen B treatment in Session 2. Regimen A: 50 mg Albiglutide Liquid Auto-injector + Placebo lyophilized DCC Pen injector. Regimen B: 50 mg Albiglutide lyophilized DCC Pen injector + Placebo Liquid Auto-injector. A minimum of an 8-week washout period between study treatment administration of Session 1 and Session 2.
Subjects will be receive Regimen B treatment in Session 1 followed by Regimen A treatment in Session 2. Regimen A: 50 mg Albiglutide Liquid Auto-injector + Placebo lyophilized DCC Pen injector. Regimen B: 50 mg Albiglutide lyophilized DCC Pen injector + Placebo Liquid Auto-injector. A minimum of an 8-week washout period between study treatment administration of Session 1 and Session 2.
Outcomes
Primary Outcome Measures
Area under the plasma concentration-time curve (AUC) from 0 to the last measurable concentration (AUC 0-t) for albiglutide in session 1 and 2
PK blood samples will be collected for determination of albiglutide plasma concentrations and (AUC 0-t).
AUC from 0 to infinity (AUC [0-inf]) for albiglutide in session 1 and 2
PK blood samples will be collected for determination of albiglutide plasma concentrations AUC(0-inf).
Peak plasma concentration (Cmax) for albiglutide in session 1 and 2
PK blood samples will be collected for determination of albiglutide Cmax.
Secondary Outcome Measures
Time to maximal concentration (Tmax) for albiglutide in session 1 and 2
PK blood samples will be collected for determination of albiglutide Tmax.
Clearance (CL/F) for albiglutide in session 1 and 2.
PK blood samples will be collected for determination of albiglutide CL/F
Volume of distribution (V/F) for albiglutide in session 1 and 2
PK blood samples will be collected for determination of albiglutide V/F
Number of subjects with adverse events (AE) and clinical observations as a measure of safety and tolerability
AE will be collected during the study. Intensity of AE will be captured
Safety as assessed by 12-lead electrocardiogram (ECG)
Single 12-lead ECGs will be obtained at the specified time points during the study using an ECG machine that automatically calculates the heart rate and other measures.
Safety as assessed by systolic, diastolic blood pressure, and pulse rate measurements
Systolic and diastolic pressure and pulse rate will be measured at specified time point
Immunogenicity as assessed by enzyme-linked immunosorbent assay (ELISA) and hypersensitivity reactions.
Immunogenicity serum samples will be collected at specified time points to assess the presence of anti-drug antibodies through enzyme-linked immunosorbent assay (ELISA) method.
Half-life (T1/2) for albiglutide in session 1 and 2
PK blood samples will be collected for determination of albiglutide T1/2.
Composite of hematology parameters as a measure of safety
The following hematology parameters will be measured: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, Reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH Concentration, white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
Composite of clinical chemistry parameters as a measure of safety
The following clinical chemistry parameters will be measured: blood urea nitrogen (BUN), creatinine, fasting glucose, uric acid, thyroid-stimulating hormone (TSH), potassium, sodium, calcium, phosphorus, magnesium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, gamma glutamyl transferase (GGT), chloride, total and direct bilirubin, total protein, albumin, total carbon dioxide, and fasting triglycerides.
Composite of urinalysis parameters as a measure of safety
The following urinalysis parameters will be measured: specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones by dipstick; microscopic examination (if blood or protein is abnormal), microalbumin, creatinine, albumin/creatinine ratio, blood, leukocyte esterase, and nitrites.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02660736
Brief Title
Bioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects
Official Title
A Randomized, Double-blind, Single-dose, Crossover Study to Compare Two Albiglutide Drug Products for Bioequivalence in Healthy Adult Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Albiglutide (Alb) is a novel analogue of glucagon-like peptide-1 (GLP-1) has been developed and approved for the treatment of type 2 diabetes mellitus. 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 use of a liquid product in a ready-to-use single dose auto-injector. To support the development of the liquid auto-injector product, this healthy volunteer bioequivalence study will be conducted to compare the liquid drug product to the currently available lyophilized product. This is Phase I, randomized, double-blind, double dummy, single-dose, 2-period crossover study in healthy volunteers. This study will compare the pharmacokinetics and safety of the albiglutide 50 mg liquid drug product with the albiglutide 50 mg commercial lyophilized drug product.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Albiglutide, Randomized, Pharmacokinetics, GSK716155, Bioequivalence study
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Regimen AB
Arm Type
Experimental
Arm Description
Subjects will be receive Regimen A treatment in Session 1 followed by Regimen B treatment in Session 2.
Regimen A: 50 mg Albiglutide Liquid Auto-injector + Placebo lyophilized DCC Pen injector.
Regimen B: 50 mg Albiglutide lyophilized DCC Pen injector + Placebo Liquid Auto-injector.
A minimum of an 8-week washout period between study treatment administration of Session 1 and Session 2.
Arm Title
Regimen BA
Arm Type
Experimental
Arm Description
Subjects will be receive Regimen B treatment in Session 1 followed by Regimen A treatment in Session 2.
Regimen A: 50 mg Albiglutide Liquid Auto-injector + Placebo lyophilized DCC Pen injector.
Regimen B: 50 mg Albiglutide lyophilized DCC Pen injector + Placebo Liquid Auto-injector.
A minimum of an 8-week washout period between study treatment administration of Session 1 and Session 2.
Intervention Type
Drug
Intervention Name(s)
Albiglutide Liquid Auto-injector
Intervention Description
Albiglutide liquid is provided as a fixed-dose, disposable auto-injector containing albiglutide liquid (50 mg). The auto-injector delivers the study treatment in an injection volume of 1.0 mL for the 50 mg dose
Intervention Type
Drug
Intervention Name(s)
Albiglutide Lyophilized DCC Pen Injector
Intervention Description
Albiglutide is supplied as prefilled DCC Pen Injector. Each DCC contains lyophilized albiglutide 50 mg. When the injector pen product is reconstituted a neutral, isotonic solution is produced. The pen delivers albiglutide in an injection volume of 0.5 mL
Intervention Type
Drug
Intervention Name(s)
Placebo Liquid Auto-injector
Intervention Description
Liquid albiglutide matching placebo is provided as a fixed-dose, disposable autoinjector containing placebo liquid. The auto-injector delivers the placebo in an injection volume of 1.0 mL for the 50 mg placebo dose.
Intervention Type
Drug
Intervention Name(s)
Placebo Lyophilized DCC Pen injector
Intervention Description
Placebo is supplied as prefilled DCC Pen Injector. Each DCC contains matching placebo. When the injector pen product is reconstituted a neutral, isotonic placebo solution is produced. The pen delivers the placebo in an injection volume of 0.5 mL.
Primary Outcome Measure Information:
Title
Area under the plasma concentration-time curve (AUC) from 0 to the last measurable concentration (AUC 0-t) for albiglutide in session 1 and 2
Description
PK blood samples will be collected for determination of albiglutide plasma concentrations and (AUC 0-t).
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Title
AUC from 0 to infinity (AUC [0-inf]) for albiglutide in session 1 and 2
Description
PK blood samples will be collected for determination of albiglutide plasma concentrations AUC(0-inf).
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Title
Peak plasma concentration (Cmax) for albiglutide in session 1 and 2
Description
PK blood samples will be collected for determination of albiglutide Cmax.
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Secondary Outcome Measure Information:
Title
Time to maximal concentration (Tmax) for albiglutide in session 1 and 2
Description
PK blood samples will be collected for determination of albiglutide Tmax.
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Title
Clearance (CL/F) for albiglutide in session 1 and 2.
Description
PK blood samples will be collected for determination of albiglutide CL/F
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Title
Volume of distribution (V/F) for albiglutide in session 1 and 2
Description
PK blood samples will be collected for determination of albiglutide V/F
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2
Title
Number of subjects with adverse events (AE) and clinical observations as a measure of safety and tolerability
Description
AE will be collected during the study. Intensity of AE will be captured
Time Frame
Up to 21 weeks
Title
Safety as assessed by 12-lead electrocardiogram (ECG)
Description
Single 12-lead ECGs will be obtained at the specified time points during the study using an ECG machine that automatically calculates the heart rate and other measures.
Time Frame
Screening, Day -1, Day 4, and Day 35 in both sessions 1 and 2
Title
Safety as assessed by systolic, diastolic blood pressure, and pulse rate measurements
Description
Systolic and diastolic pressure and pulse rate will be measured at specified time point
Time Frame
Up to 21 weeks
Title
Immunogenicity as assessed by enzyme-linked immunosorbent assay (ELISA) and hypersensitivity reactions.
Description
Immunogenicity serum samples will be collected at specified time points to assess the presence of anti-drug antibodies through enzyme-linked immunosorbent assay (ELISA) method.
Time Frame
Day 1 in both sessions and Day 13 in session 1 and follow-up visit
Title
Half-life (T1/2) for albiglutide in session 1 and 2
Description
PK blood samples will be collected for determination of albiglutide T1/2.
Time Frame
Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2.
Title
Composite of hematology parameters as a measure of safety
Description
The following hematology parameters will be measured: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, Reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH Concentration, white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
Time Frame
Up to 21 weeks
Title
Composite of clinical chemistry parameters as a measure of safety
Description
The following clinical chemistry parameters will be measured: blood urea nitrogen (BUN), creatinine, fasting glucose, uric acid, thyroid-stimulating hormone (TSH), potassium, sodium, calcium, phosphorus, magnesium, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, gamma glutamyl transferase (GGT), chloride, total and direct bilirubin, total protein, albumin, total carbon dioxide, and fasting triglycerides.
Time Frame
Up to 21 weeks
Title
Composite of urinalysis parameters as a measure of safety
Description
The following urinalysis parameters will be measured: specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones by dipstick; microscopic examination (if blood or protein is abnormal), microalbumin, creatinine, albumin/creatinine ratio, blood, leukocyte esterase, and nitrites.
Time Frame
Up to 21 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Between 18 and 65 years of age.
Healthy.
Subject is a nonsmoker.
Subject's body mass index (BMI) is >=18 kilogram/meter square (kg/m^2) and <=30 kg/m^2
Male or
Female
Exclusion Criteria:
Alanine aminotransferase (ALT) >1.5 x upper limit of normal range (ULN)
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities
QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 millisecond (msec).
Systolic blood pressure is >=140 millimeter of mercury (mmHg) at Screening;
Diastolic blood pressure is >=90 mmHg at Screening;
Heart rate is >100 beats/min at Screening.
estimated glomerular filtration rate (eGFR) <=80 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) at Screening.
Fasting triglyceride level >300 milligram per deciliter (mg/dL) at Screening.
History of significant cardiovascular or pulmonary dysfunction prior to Screening.
History of thyroid dysfunction or an abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at Screening.
History of gastrointestinal surgery that could influence gastric emptying (e.g., gastrectomy, gastric bypass).
History of pancreatitis.
Personal or family history of multiple endocrine neoplasia type 2.
Personal or family history of medullary carcinoma of the thyroid.
Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days.
History of regular alcohol consumption within 6 months of the study.
Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
Subject has previously received any GLP-1 mimetic compound (eg., exenatide, liraglutide, lixisenatide, dulaglutide).
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
A positive pre-study drug/alcohol screen.
A positive test for human immunodeficiency virus (HIV) antibody.
Subject has donated blood in excess of 500 mL within 56 days prior to dosing or intention of donating in the month after completing the study.
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).
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30063297
Citation
Shaddinger BC, Vlasakakis G, Soffer J, Thorpe KM, Hatch D, Nino AJ. A Randomized, Double-Blind, Single-Dose, Crossover Study to Demonstrate the Bioequivalence of 2 Formulations of Albiglutide in Healthy Adult Participants. Clin Pharmacol Drug Dev. 2019 Apr;8(3):361-370. doi: 10.1002/cpdd.606. Epub 2018 Jul 31.
Results Reference
derived
Learn more about this trial
Bioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects
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