Cross-Over Study to Assess the Cardiovascular Effects of GSK2336805

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01424540
First received: August 25, 2011
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Hepatitis B, Chronic
Drug: GSK2336805 150mg
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Single Dose, Cross-Over Study to Assess the Cardiovascular Effects of GSK2336805 in Healthy Adult Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of subjects with a change in ejection fraction greater than 10 percent [ Time Frame: 10 hours ] [ Designated as safety issue: Yes ]
    Echocardiographic measures of contractility


Secondary Outcome Measures:
  • Number of subjects with electrocardiogram (ECG) parameters out of range [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]
    Cardiovascular measures

  • Number of subjects with vital signs out of range [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Cardiovascular measures

  • Number of subjects with adverse events [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    tolerability

  • Number of subjects using concurrent medication [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Concomitant medications

  • Number of subjects with laboratory values out of range [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Labs

  • Area under the curve (0-24) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • Maximum observed concentration (Cmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • Terminal phase half-life [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • Lag time before observation of drug concentrations in sampled matrix [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • Time of occurrence of Cmax [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • Concentration at 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    PK parameter

  • Correlation between concentration and various safety parameters [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Safety, PK

  • B-type natriuretic peptide (BNP) lab result [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Cardiac biomarkers

  • Troponin lab results [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Cardiac biomarkers


Enrollment: 20
Study Start Date: September 2011
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
GSK2336805 150mg
Drug: GSK2336805 150mg
Single Dose
Placebo Comparator: Treatment B
GSK2336805 Placebo
Other: Placebo
Single Dose

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424540

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01424540     History of Changes
Other Study ID Numbers: 115535
Study First Received: August 25, 2011
Last Updated: July 12, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic

ClinicalTrials.gov processed this record on July 26, 2014