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PK Study of IV Formulation of GW856553

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01039961
First received: December 23, 2009
Last updated: June 13, 2017
Last verified: June 2017
  Purpose
The purpose of this study is to evaluate the safety of an IV infusion of GW856553 in healthy volunteers.

Condition Intervention Phase
Cardiovascular Disease Drug: losmapimod 1 mg Drug: losmapimod Drug: losmapimod 15 mg Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Evaluation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Intravenous Dose(s) and a Single Oral Dose of GW856553 in Healthy Volunteers

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • General safety and tolerability endpoints include changes in clinical laboratory assessments, spontaneous AE reporting, ECGs, vital signs and nursing/physician observations. [ Time Frame: Up to 15 days post IV infusion. ]

Secondary Outcome Measures:
  • pHSP27 measurements [ Time Frame: Up to 24 hours post dose. ]
  • hsCRP measurements [ Time Frame: Up to 24 hours post dose. ]
  • Maximum Plasma Concentration [Cmax] [ Time Frame: Up to 24 hours post dose ]
  • Area Under the Curve [AUC] [ Time Frame: Up to 24 hours post dose ]
  • Time of maximum plasma concentation [Tmax] [ Time Frame: Up to 24 hours post dose ]
  • Half life [T1/2] [ Time Frame: Up to 24 hours post dose ]

Enrollment: 16
Actual Study Start Date: February 2, 2010
Study Completion Date: April 15, 2010
Primary Completion Date: April 15, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 mg IV
Unit Dose Strength: 0.4 mg/mL
Drug: losmapimod 1 mg
IV infusion
Experimental: ?mg IV
dose to be determined based on PK of first IV dose
Drug: losmapimod
IV infusion (dose to be determined based on PK from first dose)
Experimental: 15 mg (oral)
two 7.5 mg tablets
Drug: losmapimod 15 mg
oral, two 7.5 mg tablets

Detailed Description:

The aims of this study are to evaluate the safety and tolerability of single intravenous (IV) doses of GW856553 in healthy adult subjects and to investigate the relationship between PK and PD markers within the first few hours following administration of study drug to support progression of this formulation into a patient population.

Subjects in Cohort 1 (n=4) will receive a single 1mg IV dose (given as a 15 minute infusion) of GW856553. Safety, tolerability and PK exposures will be reviewed, and in an optional cohort (Cohort 2) (n=4), the dose may be adjusted upward or downward based on data from Cohort 1. Based on the results from Cohort 1 (and Cohort 2 if required), Cohort 3 (n=12) will be dosed appropriately to receive a single IV 15 minute infusion of GW856553.

After a one week washout, Cohort 3 subjects will receive a single oral dose of 15mg GW856553. Access to both IV and oral PK in the same individuals will permit calculation of absolute bioavailability for the oral dose. Subjects will be resident in the research unit from the morning prior to dosing until after the last PK blood sample is collected at 24 hours after the dose of study drug (excluding any washout period).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • AST, ALT, alkaline phosphatase and bilirubin ≤ 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 cardiac monitoring.
  • Male or female between 18 and 75 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 or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhoea
  • Male subjects must agree to use contraception from the time of the first dose of study medication until seven days following the last dose.
  • Body weight >50kg (110 pounds) and body mass index (BMI) within the range >19 and <30kg/m2.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • QTcB or QTcF < 450 msec.

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 an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125ml) of wine or 1 (25ml) measure of spirits.
  • Treatment with an investigational product within 90 days or 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to dosing in this study.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Where participation in the study would result in donation of blood or blood products in excess of 500mL 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.
  • Taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), 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 until completion of the follow-up visit, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study.
  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: NCT01039961

Locations
United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113022
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01039961     History of Changes
Other Study ID Numbers: 113022
Study First Received: December 23, 2009
Last Updated: June 13, 2017
Individual Participant Data  
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
healthy volunteers
IV formulation study

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on June 27, 2017