Cross-Over Study to Assess the Cardiovascular Effects of GSK2336805

A Randomized, Double Blind, Single Dose, Cross-Over Study to Assess the Cardiovascular Effects of GSK2336805 in Healthy Adult Volunteers

This is a single-center, randomized, two part, double-blind, crossover study in healthy adult subjects to assess the effect of a single dose of GSK2336805 150mg on cardiac function comparing with placebo using echocardiography as a primary assessment modality

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: GSK2336805 150mg; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• 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 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5xUpper Limit of Normal (ULN).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including [medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included at the discretion of the Investigator only if the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, oophorectomy, or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea.

Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit.

• Body weight greater than or equal to 50 kilogram (kg) for men and 45 kg for women. Body mass index (BMI) between 18.5-30 inclusive will be allowed.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Subject has demonstrated an adequate echocardiographic window.
• QTcB less than 450 milliseconds (msec).

Exclusion Criteria:

• A positive pre-study Hepatitis B surface antigen,positive Hepatitis C antibody, or a positive test for HIV 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.
• History of regular alcohol consumption within 6 months of 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).
• 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.
• 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mililiters within a 56 day period.
• Pregnant females as determined by positive [serum or urine] hCG test at screening or prior to dosing.
• 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.
• Subjects who have asthma or a history of asthma.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication.
• Left ventricular ejection fraction less than 55% at screening.
• The subject's systolic blood pressure is outside the range of 90-140, or diastolic blood pressure is outside the range of 45-90 or heart rate is outside the range of 50-100beats per minute for female subjects or 45-100 beats per minute for male subjects.
• Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):

Males-Heart rate less than 45 and greater than 100 beats per minute (bpm). Females-Heart rate less than 50 and greater than 100 bpm Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization).

Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome). Sinus Pauses greater than 3 seconds. Any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety for the individual subject. Non-sustained or sustained ventricular tachycardia ( greater than or equal to 3 consecutive ventricular ectopic beats).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; GSK2336805 150mg	Drug: GSK2336805 150mg; Single Dose
Placebo Comparator: Treatment B; GSK2336805 Placebo	Other: Placebo; Single Dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with a change in ejection fraction greater than 10 percent	Echocardiographic measures of contractility	10 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with electrocardiogram (ECG) parameters out of range	Cardiovascular measures	3 hours
Number of subjects with vital signs out of range	Cardiovascular measures	24 hours
Number of subjects with adverse events	tolerability	24 hours
Number of subjects using concurrent medication	Concomitant medications	24 hours
Number of subjects with laboratory values out of range	Labs	24 hours
Area under the curve (0-24)	PK parameter	24 hours
Maximum observed concentration (Cmax)	PK parameter	24 hours
Terminal phase half-life	PK parameter	24 hours
Lag time before observation of drug concentrations in sampled matrix	PK parameter	24 hours
Time of occurrence of Cmax	PK parameter	24 hours
Concentration at 24 hours	PK parameter	24 hours
Correlation between concentration and various safety parameters	Safety, PK	24 hours
B-type natriuretic peptide (BNP) lab result	Cardiac biomarkers	24 hours
Troponin lab results	Cardiac biomarkers	24 hours

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Wilfret DA, Adkison KK, Jones LA, Lou Y, Gan J, Spreen W. Echocardiogram study to evaluate the effect of the novel hepatitis C virus NS5A inhibitor GSK2336805 on cardiac contractility in healthy subjects. Antimicrob Agents Chemother. 2013 Oct;57(10):5141-3. doi: 10.1128/AAC.00668-13. Epub 2013 Jul 15.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): October 3, 2011
• Study Completion (Actual): October 3, 2011

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimate): August 29, 2011

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C
• Other Study ID Numbers: 115535