The study will investigate whether GSK1362885 is safe and well-tolerated when administered
to normal healthy subjects. The study will also measure blood levels of the study drug to
determine how the body processes the drug (pharmacokinetics) and what effects the drug has
on the body (pharmacodynamics).
Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following
criteria apply:
- Healthy as determined by a responsible physician, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
monitoring.
- Male or female between 18 and 55 years of age, inclusive, at the time of signing the
informed consent.
- A female subject is eligible to participate if she is of non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy;
or postmenopausal defined as 12 months of spontaneous amenorrhea
- BMI within the range 20. 0 to 31. 9 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- Normal cardiac function and ECG parameters, as per protocol.
- No significant rhythm abnormalities in the Screening Holter ECG recording.
Exclusion Criteria:
A subject will not be eligible for inclusion in this study if any of the following
criteria apply:
- The subject has a positive pre-study drug/alcohol screen. A minimum list of
tobacco/drugs that will be screened include amphetamines, barbiturates, cocaine,
opiates, cannabinoids and benzodiazepines.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco-
or nicotine-containing products within 6 months prior to screening.
- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >14 drinks/week for men or >7 drinks/week for women.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of glycogen storage disease
- Unable or unwilling to abstain from:
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices for 7 days prior
to the first dose of study medication until the final post-dose assessment at each
treatment level.
- Caffeine-or xanthine-containing products for 24 hours prior to dosing until the final
post-dose assessment at each treatment level.
- Use of illicit drugs
- Alcohol for 24 hours prior to dosing until final post-dose assessment at each
treatment level.
- Strenuous exercise for 48 hours prior to each blood collection for clinical
laboratory tests. Subjects may participate in light recreational activities during
studies (e. g., watch television, read).
- History of uncorrected thyroid dysfunction or an abnormal thyroid function test
assessed by TSH and free T4 at screening
- Pregnant females as determined by positive serum or urine hCG test at screening or
prior to dosing.
- Lactating females.
- History of any gastrointestinal or hepatic conditions that could impact absorption of
the investigational compound.
- Significant ECG abnormalities as defined per protocol
- Resting systolic blood pressure < 80 mmHg or > 150 or diastolic blood pressure < 60
mmHg or > 90 mmHg at screening. Resting heart rate is outside the range of 45 to 100
bpm.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody.
- A positive test for HIV antibody.
- A fasting triglyceride level >400mg/dL (4. 45mmol/L).
- Anemia defined by hemoglobin concentration <11. 0g/dL for males or <10. 0g/lL for
females.
- Significant renal disease as manifested by one or more of the following:
- Creatinine clearance <80 mL/min. (estimated from serum creatinine (SCr) and
demographic data using the MDRD calculation):
- Urine protein/creatinine (mg/mg) ratio >2. 5; or urine albumin concentration >300 g/mg
of creatinine.
- Known loss of a kidney either by surgical ablation, injury, or disease
- Subjects with values outside the specified ranges for the following key clinical
laboratory tests at Screening and at readmission for each treatment period.
Laboratory tests may be repeated once to confirm eligibility prior to dosing:
- Liver function tests: ALT, Direct Bilirubin, or Albumin more than 10% outside the
normal reference range (<0. 9 x LLN or >1. 1 x ULN)
- Electrolytes: Sodium more than +/- 5mEq/L outside the normal reference range,
potassium or Calcium more than 10% outside the normal reference range (<0. 9 x LLN or
>1. 1.x ULN).
- Metabolic: Glucose more than 10% outside the normal reference range (<0. 9 x LLN or
>1. 1 x ULN), Total Cholesterol >240mg/dl.
- Muscle: CPK >2 x ULN.
- Hematology: Hemoglobin, WBC Neutrophils, or Platelets more than 10% outside the
normal reference range (<0. 9 x LLN or >1. 1. x ULN).
- 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, herbal and dietary
supplements (including St John's Wort) is prohibited from 7 days (or 14 days if the
drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to
the first dose of study medication until the final post-dose assessment, unless in
the opinion of the Investigator and GSK Medical Monitor the medication will not
interfere with the study procedures or compromise subject safety.
- 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.
- Unable or unwilling to discontinue aspirin use during the study. Subjects who are
taking low-dose aspirin for cardiovascular prophylaxis (81 mg or less) are eligible
to participate in the study, but the aspirin must be discontinued from Screening
through the Follow-up visit.
Other
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- As a result of the medical interview, physical examination, or screening
investigations, the investigator considers the subject unfit for the study.
- Subject is either an immediate family member of a participating investigator, study
coordinator, employee of an investigator; or is a member of the staff conducting the
study.
