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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimen AB | Experimental | 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. |
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| Regimen BA | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albiglutide Liquid Auto-injector | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2 |
| 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). | Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2 |
| Peak plasma concentration (Cmax) for albiglutide in session 1 and 2 | PK blood samples will be collected for determination of albiglutide Cmax. | Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to maximal concentration (Tmax) for albiglutide in session 1 and 2 | PK blood samples will be collected for determination of albiglutide Tmax. | Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2 |
| Clearance (CL/F) for albiglutide in session 1 and 2. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Austin | Texas | 78744 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30063297 | Derived | 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. |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Albiglutide Lyophilized DCC Pen Injector | Drug | 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 |
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| Placebo Liquid Auto-injector | Drug | 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. |
|
| Placebo Lyophilized DCC Pen injector | Drug | 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. |
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PK blood samples will be collected for determination of albiglutide CL/F |
| Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2 |
| Volume of distribution (V/F) for albiglutide in session 1 and 2 | PK blood samples will be collected for determination of albiglutide V/F | Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 2 |
| 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 | Up to 21 weeks |
| 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. | Screening, Day -1, Day 4, and Day 35 in both sessions 1 and 2 |
| 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 | Up to 21 weeks |
| 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. | Day 1 in both sessions and Day 13 in session 1 and follow-up visit |
| Half-life (T1/2) for albiglutide in session 1 and 2 | PK blood samples will be collected for determination of albiglutide T1/2. | Predose (0), 24, 48, 72, 96, 120, 216, 312, 480, 672, and 840 hours post-dose in both sessions 1 and 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. | Up to 21 weeks |
| 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. | Up to 21 weeks |
| 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. | Up to 21 Weeks |
| D004700 | Endocrine System Diseases |