An Open-label Single Dose Randomized, Parallel Group Study Followed by Single-blind Repeat Dosing, to Compare the Relative Bioavailability of GSK2212836.

An Open-label Single Dose Randomized, Parallel Group Study Followed by Single-blind Repeat Dosing, to Compare the Relative Bioavailability of GSK2212836

Sixteen healthy subjects will be randomized to each of the 3 parallel treatment groups. Eligible subjects will check in to the clinical unit on Day -2 and have 24-hr pharmacokinetic collections on Day -1 and on Day 1. Once the pharmacokinetic parameters of the formulations have been analyzed, doses of GSK2212836 will be selected for further study in Part B. Subjects from Part A will participate in Part B.

Part B is a single blind, randomized, placebo controlled study that will consist of a 2-week repeat dose period with 3 dose levels and one dose of the marketed formulation of GSK2212836. Subjects will check in to the clinical unit on Day -3; will participate in a test meal on Day -2 and have 24-hr baseline pharmacokinetic profiles on Day -1 and Day 1. Subjects will be released from the clinic on Day 2, and return for daily dosing on Days 3 through 12. On Day 6, they will also have a brief outpatient visit. Subjects will check into the clinic again on the evening of Day 12, and on Day 13 they will again have 24-hr pharmacokinetic profiles collected. Subjects will be released from the clinical research unit on Day 14, following a test meal, triglyceride sampling and check-out assessments, and will be released from the study 5-10 days later after completing a follow up visit.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: GSK2212836; Drug: GSK2212836

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14202
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AST, ALT, alkaline phosphatase and bilirubin less than 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including [medical history, physical examination, laboratory tests and ECGs. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of Child-bearing potential and agrees to use one of the contraception methods listed in the protocol.
• Body weight greater than or equal to 50kg (110 lbs) for men and greater than or equal to 45 kg for women and BMI within the range 24-34kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined as:
• 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 four new chemical entities within 12 months prior to the first dosing day.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• Use of omega-3 fatty acid supplements and/or fish or fish oil products from screening until final assessment and unwilling to abstain from eating oily fish (salmon, albacore tuna, mackerel, sardines, etc.) during the course of the study.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• History of sensitivity or known allergy to fish and /or shellfish.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive hCG test at screening (serum) or prior to dosing (urine).
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Unable to abstain from smoking tobacco- or use of nicotine-containing products while in the clinic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Three groups of sixteen healthy subjects will be randomized to single doses of 3 different formulations of GSK2212836.	Drug: GSK2212836; Treatment A - GSK2212836 test formulation 1, Treatment B - GSK2212836 test formulation 2, or Treatment C -GSK2212836 marketed formulation.; Drug: GSK2212836; Treatment D - low dose of GSK2212836 test formulation, Treatment E - medium dose of GSK2212836 test formulation, Treatment F - high dose of GSK2212836 test formulation, Treatment G - GSK2212836 marketed formulation, or Placebo.
Experimental: Part B; Four cohorts of at least 10 subjects will participate in a 2-week repeat dose period with 4 dose levels (based on data obtained in Part A) of the GSK2212836 test formulations or placebo.	Drug: GSK2212836; Treatment A - GSK2212836 test formulation 1, Treatment B - GSK2212836 test formulation 2, or Treatment C -GSK2212836 marketed formulation.; Drug: GSK2212836; Treatment D - low dose of GSK2212836 test formulation, Treatment E - medium dose of GSK2212836 test formulation, Treatment F - high dose of GSK2212836 test formulation, Treatment G - GSK2212836 marketed formulation, or Placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: To determine the total (AUC(0 to infinity)) and peak (Cmax) exposure of GSK2212836	24 hours
Part B: PK parameters AUC(0-24h) and Cmax following 14 days of dosing with GSK2212836	14 days
Part A: To assess the relative bioavailability of GSK2212836 test capsules vs the reference formulation GSK2213836	24 hours
Part B: To estimate the accumulation and dose proportionality of GSK2212836 after repeat dosing of the test formulation	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Safety and tolerability parameters following single doses of GSK2212836 test formulation including adverse events, clinical laboratory, ECGs and vital signs assessments.	24 hours
Part A: Secondary PK parameters including: tmax, t1/2 and baseline-corrected AUC(0-24h)	24 hours
Part B: Safety and tolerability parameters following repeat doses of GSK2212836 test formulation including adverse events, clinical laboratory, ECGs and vital signs assessments	14 days
Part B: Secondary PK parameters including: tmax, t1/2	14 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Hussey EK, Portelli S, Fossler MJ, Gao F, Harris WS, Blum RA, Lates CD, Gould E, Abu-Baker O, Johnson S, Reddy KK. Relative Bioavailability of an Emulsion Formulation for Omega-3-Acid Ethyl Esters Compared to the Commercially Available Formulation: A Randomized, Parallel-Group, Single-Dose Study Followed by Repeat Dosing in Healthy Volunteers. Clin Pharmacol Drug Dev. 2012 Jan;1(1):14-23. doi: 10.1177/2160763X11431107.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2009
• Primary Completion (Actual): January 4, 2010
• Study Completion (Actual): January 4, 2010

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimate): October 16, 2009

Study Record Updates

• Last Update Posted (Actual): June 22, 2017
• Last Update Submitted That Met QC Criteria: June 21, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: hypertriglyceridemia; relative bioavailability; GSK2212836
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: 113412

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 113412
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register