Bioequivalence Study of Two Albiglutide Drug Products in Healthy Adult Subjects

NCT02660736 | Completed Phase 1

• 1 other identifier: 201287
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Albiglutide; Randomized; Pharmacokinetics; GSK716155; Bioequivalence study

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (11)

• Time to maximal concentration (Tmax) for albiglutide in session 1 and 2

  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.

  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

  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

  Up to 21 weeks

• Safety as assessed by 12-lead electrocardiogram (ECG)

  Screening, Day -1, Day 4, and Day 35 in both sessions 1 and 2

Study Arms (2)

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.

Drug: Albiglutide Liquid Auto-injector; Drug: Albiglutide Lyophilized DCC Pen Injector; Drug: Placebo Liquid Auto-injector; Drug: Placebo Lyophilized DCC Pen injector

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.

Drug: Albiglutide Liquid Auto-injector; Drug: Albiglutide Lyophilized DCC Pen Injector; Drug: Placebo Liquid Auto-injector; Drug: Placebo Lyophilized DCC Pen injector

Interventions

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

Regimen AB; Regimen BA

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

Regimen AB; Regimen BA

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.

Regimen AB; Regimen BA

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.

Regimen AB; Regimen BA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• 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.

  PMID: 30063297 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2016
• First Posted: January 21, 2016
• Study Start: February 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: November 9, 2016

Record last verified: 2016-11

Locations

US (1)