Study Of Pharmacokinetics and Pharmacodynamics Effects Of GSK256073A On Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00488449
First received: June 18, 2007
Last updated: May 31, 2012
Last verified: February 2011
  Purpose

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
Dyslipidaemias
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

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
  Eligibility

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

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
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: NCT00488449

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

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov 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
GSK256073A,

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 22, 2014