A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Food Effect of Single or Repeat Doses of GSK2793660 in Healthy Subjects

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Brief Title

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Food Effect of Single or Repeat Doses of GSK2793660 in Healthy Subjects

Official Title

A Randomised, Double-blind (Sponsor Unblind), Placebo-controlled, Two Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Single or Repeat Doses of GSK2793660 in Healthy Subjects

Brief Summary

      This study is the first administration of GSK2793660 to humans and will evaluate the safety,
      tolerability, PK and PD of single oral ascending doses of GSK2793660, and of repeat oral
      doses of GSK2793660 in healthy subjects. The study will comprise two parts (Part A and Part
      B). Part A will consist of two cohorts of subjects, each taking part in a three-way cross
      over study, with ascending doses of GSK2793660 and placebo. Available safety, PK and PD data
      will be reviewed before each dose escalation. This will be followed by a food-effect arm in
      the cohort that received what is deemed to be the target clinical dose. Part B is planned to
      consist of up to two cohorts of subjects, each taking part in one 14 day repeat dose study
      period. Subjects will be dosed on Day 1 and then on Days 3-15. It is planned that two doses
      will be evaluated. The dose(s) to be tested will be selected based on safety, PK, and PD from
      Part A. The study is intended to provide sufficient confidence in the safety profile of the
      molecule and information on target engagement to allow progression to further studies.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety and tolerability of GSK2793660 as assessed by vital signs in Part A and Part B

Secondary Outcome

 Composite of PK parameters for GSK2793660 in Part A and Part B

Condition

Bronchiectasis

Intervention

GSK2793660 solution

Study Arms / Comparison Groups

 Cohort 1- Part A
Description:  This cohort will follow an interlocking design with Cohort 2 - Part A. Out of the 9 healthy subjects in this cohort, 3 subjects will receive placebo and 6 subjects will receive GSK2793660 according to randomization schedule in three single-dose study periods. Drug administration will be staggered over 2 days in each period. On Day 1, only 1 subject will receive GSK2793660 and 1 subject will receive placebo. The remaining subjects will be dosed on Day 2 of each treatment period assuming adequate safety from Day 1. Placebo administration and an escalation of GSK2793660 from 0.5 mg, to 3 mg, and 20 mg in the subsequent periods, will be done with a minimum washout period of 13 days between doses. If the target clinical dose is determined as being one of the doses administered to this cohort, they will have an additional study period for the administration of target clinical dose GSK2793660 following the standard Food and drug administration (FDA) high fat/high calorie meal.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

33

Start Date

January 28, 2014

Completion Date

October 31, 2014

Primary Completion Date

October 31, 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, and laboratory tests. A
             subject with a clinical abnormality or laboratory parameters outside the reference
             range, and which is not a part of an eligibility criterion, for the population being
             studied may be included only if the Investigator and GSK medical monitor consider the
             finding is unlikely to introduce additional risk factors and will not interfere with
             the study procedures and outcome.

          -  Male or female between 18 and 55 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, removal of both
             ovaries or hysterectomy; or postmenopausal defined as 12 months of spontaneous
             amenorrhea [in questionable cases a blood sample with simultaneous follicle
             stimulating hormone (FSH) >21.7 International units per liter (IU/L) and oestradiol
             <110 picomole per liter (pmol/L) is confirmatory]. Females on hormone replacement
             therapy (HRT) and whose menopausal status is in doubt will be required to use one of
             the contraception methods listed in the protocol if they wish to continue their HRT
             during the study. Otherwise, they must discontinue HRT to allow confirmation of
             post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4
             weeks should elapse between the cessation of therapy and the blood draw; this interval
             depends on the type and dosage of HRT. Following confirmation of their post-menopausal
             status, they can resume use of HRT during the study without use of a contraceptive
             method.

          -  Male subjects with female partners of child-bearing potential must agree to use one of
             the approved contraception methods as detailed 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 >=50 Kilogram (kg) and Body Mass Index (BMI) within the range 19.9-30.0
             kg/meter square (m^2) (inclusive).

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Based on averaged QT duration corrected for heart rate by Fridericia's formula (QTcF)
             values of triplicate ECGs obtained over a brief recording period: Average QTcF <450
             milliseconds (msec)

          -  Systolic blood pressure <=130 millimeters of mercury (mmHg) and diastolic blood
             pressure 80 mmHg based on average values of triplicate blood pressure readings
             obtained over a brief period.

          -  Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper Limit
             of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%).

        Exclusion Criteria:

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  ECG finding of second or third degree heart block.

          -  History of regular alcohol consumption within 6 months of the study defined as: an
             average weekly intake of >21 units for males or >14 units for females. One unit is
             equivalent to 8 gram of alcohol: a half-pint (approximately 240 milliliter [mL]) of
             beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

          -  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 to heparin or heparin-induced thrombocytopenia.

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months of screening.

          -  Urinary cotinine or exhaled breath carbon monoxide (CO) levels indicative of current
             smoking or history or regular use of tobacco- or nicotine-containing products within 6
             months prior to screening.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for human immunodeficiency virus (HIV) antibody.

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period. Blood donation will not exceed 500 mL for
             the entire 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).

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.
      

Gender

All

Ages

18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

GSK Clinical Trials, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT02058407

Organization ID

200186


Responsible Party

Sponsor

Study Sponsor

GlaxoSmithKline


Study Sponsor

GSK Clinical Trials, Study Director, GlaxoSmithKline


Verification Date

September 2018