Study Of Pharmacokinetics and Pharmacodynamics Effects Of GSK256073A On Healthy Volunteers

This study has been completed.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: June 18, 2007
Last updated: May 31, 2012
Last verified: February 2011

The purpose of this study is to compare the effects of single and repeat doses of GSK256073 with placebo in HVT subjects.

Condition Intervention Phase
Healthy Subjects
Drug: GSK256073A tablets
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Diagnostic
Official Title: A Two-Part Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Oral Doses of GSK256073A, in a Randomized, Single-Blind, Dose Escalation Study in Healthy Adult Subjects

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • AEs, 12-Lead ECG, vital signs, nursing/physician observation, safety lab tests, flushing [ Time Frame: throughout the study (Parts A &B) ]
  • AUC and Cmax [ Time Frame: throughout the study (Part A & B) ]
  • Measures of accumulation ratios [ Time Frame: throughout the study (Ro, Rp, and Rs)[Part B] ]

Secondary Outcome Measures:
  • Tmax, t½, Ae, and CLr (Parts A & B) Cmax, ss, Ct, t½, Ae, CLr, and accumulation ratios (Part B) [ Time Frame: throughout the study ]
  • PD response: NEFA and TG (6 and 24 hours post- dose) [ Time Frame: (6 and 24 hours post- dose) ]
  • LDL, HDL, ApoA1, ApoA2, Apo B and Lp(a) [ Time Frame: on Days 1, 14, and 15. ]
  • Levels of GSK256073 to derive pharmacokinetic parameters following repeat dose administration.
  • Lipid levels [ Time Frame: on Days 1, 14, and 15 ]

Enrollment: 56
Study Start Date: June 2007
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GSK256073A tablets
    Other Name: GSK256073A tablets

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion criteria:

  • Healthy Adult males or females between 18 and 55 years of age, inclusive.
  • Female subjects must be of non-childbearing potential
  • Body weight > 50 kg (110 pounds) and body mass index (BMI) 19 and 31 where:
  • Subjects with QTc < 450 msec at screening (or QTc < 480 msec for subjects with Bundle Branch Block).
  • A signed and dated written informed consent prior to admission to the study.
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restriction

Exclusion criteria:

  • Systolic blood pressure < 100 mmHg or 150 mmHg and/or diastolic blood pressure = 100 mmHg at screening.
  • History of significant cardiac arrhythmias
  • Active peptic ulcer disease (PUD) and/or history of PUD within 1 year.
  • A serum uric acid concentration 8mg/dL
  • Screening test positive for H. Pylori using the non-radioactive breath test
  • History of gout and/or hyperuricemia
  • History of Gilbert's syndrome
  • A serum creatinine concentration above the normal reference range
  • History of kidney stones
  • PT and/or aPTT above the reference range
  • History of recurrent indigestion, stomach upset or diarrhea
  • Liver function tests (LFTs) or creatinine phosphokinase (CPK) 1.5X ULN
  • Screening stool test positive for occult blood
  • Screening peripheral blood smear with abnormal RBCs
  • CBC, MCV, and/or reticulocyte count corrected for haemoglobin level above the reference range at screening
  • Reduced G6PD activity
  • Serum haptoglobin outside the reference range at screening
  • Total serum LDH > 1.25% above the ULN at screening
  • Positive HIV, Hepatitis B or Hepatitis C at screening
  • The subject has a positive pre-study urine drug/ serum alcohol screen.
  • History of alcohol consumption exceeding, on average, 7 drinks/week for women or 14 drinks/week for men within 6 months of the first dose of study medication or a positive alcohol test at screening
  • History of use of tobacco or nicotine containing products within 6 months of screening or a positive urine cotinine screen
  • Use of prescription (including hormone replacement therapy) or non-prescription drugs and vitamins within 7 days or 5 half-lives prior to administration of study medication. An exception is acetaminophen which is allowed at doses of 2g/day.
  • Use of dietary/herbal supplements within 14 days prior to treatment with study medication
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • 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 physician responsible, contraindicates their participation.
  • Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
  • Unwillingness of male subjects to use a condom/spermicide
  • Pregnant or nursing women.
  • History of flushing (>1 episode annually).
  • Fasting blood glucose 110 mg/dl and/or history of type I or type II DM
  • History of intra-ocular pathology
  • History of recurrent gum bleeding
  • History of bleeding haemorrhoids
  Contacts and Locations
Please refer to this study by its identifier: NCT00488449

United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline Identifier: NCT00488449     History of Changes
Other Study ID Numbers: HMA110015
Study First Received: June 18, 2007
Last Updated: May 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Dose Escalation

Additional relevant MeSH terms:
Lipid Metabolism Disorders
Metabolic Diseases processed this record on April 17, 2014