A Single Center Four Part Study in Healthy Adult Subjects to Evaluate: the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose and Repeat Escalating Oral Doses of GSK945237; the Effect of Linezolid on Hematology Safety Parameters; and the Effects of GSK945237 and Moxifloxacin on QTc.

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01039610
• Date of registration: 23/12/2009
• Primary sponsor: GlaxoSmithKline
• Public title: A Single Center Four Part Study in Healthy Adult Subjects to Evaluate: the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose and Repeat Escalating Oral Doses of GSK945237; the Effect of Linezolid on Hematology Safety Parameters; and the Effects of GSK945237 and Moxifloxacin on QTc.
• Scientific title: A Single Center Four Part Study in Healthy Adult Subjects to Evaluate: the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose and Repeat Escalating Oral Doses of GSK945237; the Effect of Linezolid on Hematology Safety Parameters; and the Effects of GSK945237 and Moxifloxacin on QTc.
• Date of first enrolment: November 2009
• Target sample size: 0
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01039610
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Healthy as determined by a responsible physician, based on a medical evaluation
including history, physical examination, laboratory tests, cardiac monitoring. A
subject with a non-clinically significant abnormality or laboratory parameters
outside the reference range may be included only if the investigator considers that
the finding will not introduce additional risk factors and will not interfere with
the study procedures or data interpretation.

- Male or female between 18 and 60 years of age.

- A female subject is eligible to participate if she is of:

- Non-childbearing potential defined as pre-menopausal females with a documented
bilateral tubal ligation, hysterectomy, or bilateral oophorectomy; or postmenopausal
defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample
with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40
pg/ml (<140 pmol/L) is confirmatory].

- Male subjects must agree to use one of the contraception methods listed in Section
8.1. This criterion must be followed from the time of the first dose of study
medication until at least 90 days post-last dose.

- Body weight greater than 50 kg and BMI within the range 19 - 32 kg/m2 (inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

- Any clinically significant central nervous system (e.g., seizures), cardiac,
pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of
such conditions that, in the opinion of the investigator may place the subject at an
unacceptable risk as a participant in this trial or may interfere with the
absorption, distribution, metabolism or excretion of drugs.

- Any preexisting retinal condition or finding on baseline examination that, in the
opinion of the investigator, may place the subject at an unacceptable risk as a
participant in this trial or may interfere with interpretation of ophthalmologic
safety results during the conduct of the trial.

- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs
that will be screened for include amphetamines, barbiturates, cocaine, opiates,
cannabinoids and benzodiazepines.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- A positive test for HIV antibody.

- History of regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of greater than 21 units or an average daily intake of greater
than 3 units (males), or defined as an average weekly intake of greater than 14 units
or an average daily intake of greater than 2 units (females). One unit is equivalent
to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of
wine.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Use of prescription or non-prescription drugs, including vitamins above the
recommended daily intake herbal and dietary supplements within 7 days or 5 half-lives
(whichever is longer) prior to the first dose of study medication, or use of St.
John's Wort within 14 days prior to the first dose of study medication. By
exception, the volunteer may take acetaminophen (< or equal to 2 grams/day) or
ibuprofen (1600 mg/day) up to 48 hours prior to the first dose of study medication.
However, the investigator and study team can review medication use on a case by case
basis to determine if its use would compromise subject safety or interfere with study
procedures or data interpretation.

- 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 investigator or GSK
Medical Monitor, contraindicates their participation.

- The subject has donated blood within 2 months prior to dosing and/or donated plasma
within 1 week prior to dosing.

- An unwillingness of male subjects to abstain from sexual intercourse with pregnant or
lactating women, or an unwillingness of male subjects to use a condom and spermicide,
in addition to having their female partner use another form of contraception such as
an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone,
subdermal implants or a tubal ligation, if engaging in sexual intercourse with a
female partner who could become pregnant. This criterion must be followed from the
time of study medication administration and until 90 days after study medication
administration.

- Lactating females.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco-
or nicotine-containing products within 6 months prior to screening.

- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
to the first dose of study medication.

- For Part C and Part D only: Contraindications to the use of linezolid or
moxifloxacin, respectively as per the package insert [Avelox Product Information,
2008; Zyvox Product Information, 2008].



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Infections, Bacterial

Intervention(s)

Drug: GSK945237

Drug: Linezolid

Drug: Moxifloxacin

Drug: Placebo

Primary Outcome(s)

Amount excreted in urine (Ae) and renal clearance of GSK945237 [Time Frame: duration of dosing]

Change from baseline in QTc for GSk945237, moxifloxacin, and placebo [Time Frame: duration of dosing]

Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, and t1/2 of GSK945237 [Time Frame: duration of dosing]

QT interval and heart rate [Time Frame: duration of dosing]

Safety and tolerability assessments, consisting of AEs, ECGs, vital signs, clinical laboratory tests. [Time Frame: duration of dosing]

Saliva PK parameters [Time Frame: duration of dosing]

Secondary ID(s)

107895

Source(s) of Monetary Support

Please refer to primary and secondary sponsors