Clinical trial NCT00549653: A Study Investigating Blood Concentrations Of Rosuvastatin When Co-administered With GW856553 In Healthy Men
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atherosclerosis
Cardiovascular Disease
Keywords: GW856553,
drug-drug interactions,
rosuvastatin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-26
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: PK blood draws at days 14 and 28
timeFrame: days 14 and 28
Secondary outcomes:
measure: The primary pharmacokinetic endpoints of interest are AUC(0-τ) and Cmax for rosuvastatin
timeFrame: days 14, 15, 28
measure: The secondary pharmacokinetic endpoints of interest are Tmax and t1/2 for rosuvastatin
timeFrame: days 14, 15, 28
measure: Measurement of alanine aminotransferase (ALT) and maximum change from baseline in ALT in all subjects
timeFrame: days -1, 13, 14, 16, 18, 20, 22, 24, 26, 28, follow up
measure: Clinical safety data from spontaneous adverse event reporting, 12-lead ECG recording, vital sign measurement, nursing/physician observation and safety laboratory examination.
timeFrame: days -1, 13, 14, 16, 22, 26, 28, follow up
measure: Analysis of LPS induction of IL-1b, IL-6, IL-8 and TNFa, as well as additional biomarkers, as data permit.
timeFrame: day 1, 14, 21, 28
Other outcomes:
Locations:
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: