Study Of Pharmacokinetics and Pharmacodynamics Effects Of GSK256073A On Healthy Volunteers

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00488449
• Other study ID #: HMA110015
• Status: Completed
• Phase: Phase 1
• First received: June 18, 2007
• Last updated: May 31, 2012
• Start date: June 2007
• Est. completion date: November 2007

Study information

• Verified date: February 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Dyslipidaemias
• Dyslipidemias
• Healthy Subjects

Intervention

Drug:
• GSK256073A tablets

Locations

Country	Name	City	State
United States	GSK Investigational Site	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AEs, 12-Lead ECG, vital signs, nursing/physician observation, safety lab tests, flushing		throughout the study (Parts A &B)
Primary	AUC and Cmax		throughout the study (Part A & B)
Primary	Measures of accumulation ratios		throughout the study (Ro, Rp, and Rs)[Part B]
Secondary	Tmax, t½, Ae, and CLr (Parts A & B) Cmax, ss, Ct, t½, Ae, CLr, and accumulation ratios (Part B)		throughout the study
Secondary	PD response: NEFA and TG (6 and 24 hours post- dose)		(6 and 24 hours post- dose)
Secondary	LDL, HDL, ApoA1, ApoA2, Apo B and Lp(a)		on Days 1, 14, and 15.
Secondary	Levels of GSK256073 to derive pharmacokinetic parameters following repeat dose administration.
Secondary	Lipid levels		on Days 1, 14, and 15