A Study Investigating Blood Concentrations Of Rosuvastatin When Co-administered With GW856553 In Healthy Men

A Randomized, Single Blind, Repeat Dose, Placebo-controlled, Single-period, Parallel Group Study to Investigate the Safety, Tolerability and Potential Pharmacokinetic Interactions Between GW856553 and Rosuvastatin (10mg), When Co-administered in Healthy Adult Male Subjects

This study is being conducted to provide initial safety and tolerability data as well as to provide PK data on potential interactions when GW856553 and rosuvastatin are co-administered in healthy male adults

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Atherosclerosis
• Intervention / Treatment: Drug: GW856553

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Healthy adult males, 18-55 years of age, inclusive
• 50Kg >body weight <120Kg
• Body Mass Index (BMI): 19-30
• Must be within 20% of the ideal weight based on height and body frame

Exclusion criteria:

• Any medical history or clinically relevant abnormality identified on the screening medical examination, vital sign measurement, 12-lead ECG recording and/or clinical laboratory examination that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern.
• Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).
• Positive HIV antibody, Hepatitis B surface antigen, Hepatitis C antibody, or other chronic hepatic disorders at screening.
• Subjects with chronic infections such as gingivitis, periodontitis, prostatitis, gastritis, urinary track infections, or any active diseases, including tuberculosis or a history of active tuberculosis.
• Subjects with any acute infection, symptoms suggestive of sinusitis or significant trauma (burns, fractures).
• History of alcohol consumption exceeding, on average, 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of 80 proof distilled spirits) within 6 months of screening.
• Positive urine drug (including cotinine) and/or alcohol at screening.
• A history of smoking within the 3 months prior to screening.
• Use of prescription or non-prescription drugs, including (but not limited to) vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential drug inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication. An exception is acetaminophen which is allowed at doses of ≤ 2g/day.
• Participation in a clinical study where the subject has received a drug or new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
• The subject has been exposed to more than four new chemical entities within 12 months prior to the first day of dosing.
• Consumption of any fruit juices (including grapefruit juice) within 7 days prior to the first dose of study medication.
• A history of cholecystectomy or biliary tract disease including a history of liver disease with elevated liver function tests of known or unknown etiology.
• History of increased liver function tests (ALT, AST) above upper limit of normal in the past 6 months and/or liver function tests (bilirubin, ALT, AST) above upper limit of normal at Screening.
• A known history of Gilbert's Syndrome.
• History of myopathy or rhabdomyolysis.
• QTc interval > 450msec.
• An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception, such as: an intrauterine devise (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if the woman could become pregnant from the first dose of study medication until completion of follow-up procedures.
• Donation of blood in excess of 500 mL within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Hypersensitivity to rosuvastatin or any component of the rosuvastatin formulation utilised in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK blood draws at days 14 and 28	days 14 and 28

Secondary Outcome Measures

Outcome Measure	Time Frame
The primary pharmacokinetic endpoints of interest are AUC(0-τ) and Cmax for rosuvastatin	days 14, 15, 28
The secondary pharmacokinetic endpoints of interest are Tmax and t1/2 for rosuvastatin	days 14, 15, 28
Measurement of alanine aminotransferase (ALT) and maximum change from baseline in ALT in all subjects	days -1, 13, 14, 16, 18, 20, 22, 24, 26, 28, follow up
Clinical safety data from spontaneous adverse event reporting, 12-lead ECG recording, vital sign measurement, nursing/physician observation and safety laboratory examination.	days -1, 13, 14, 16, 22, 26, 28, follow up
Analysis of LPS induction of IL-1b, IL-6, IL-8 and TNFa, as well as additional biomarkers, as data permit.	day 1, 14, 21, 28

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: October 24, 2007
• First Submitted That Met QC Criteria: October 25, 2007
• First Posted (Estimate): October 26, 2007

Study Record Updates

• Last Update Posted (Estimate): June 4, 2012
• Last Update Submitted That Met QC Criteria: May 31, 2012
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: rosuvastatin; GW856553,; drug-drug interactions,
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis
• Other Study ID Numbers: PM1106502