A Safety Study in Healthy Volunteers to Evaluate Safety, How Fast the Drug is Absorbed, and the Side Effects of the Drug in Humans

• Status: Completed
• Trial end date: 2010-05-27
• Target enrollment: 0
• Participant gender: All

Summary

This study is to evaluate the safety, absorption rate and side effects associated with the study drug. Healthy volunteers will be given a single dose of the drug in Part 1. Subjects will be dosed at the same time at several different sites. In Part 2 of the study elderly volunteers will participate in a 14 day repeat dose session receiving either study drug or a placebo (sugar pill). Data from at least 7 days of safety will be reviewed from the first set of volunteers before increasing the doses for the next set. All results will be used for planning the next study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

Inclusion Criteria:

• AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

• For the first part of the study male or female greater than or equal to 18 years of age and for the second part male or female greater than or equal to 50 years of age 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. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) or values consistent with local laboratory recommended value is confirmatory.

• Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg for women within the BMI range 19-30 kg/m2 (inclusive).

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

• Single QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

• Best-corrected visual acuity better than 20/80 (Snellen equivalent) in both eyes in Part 2 only.

Exclusion Criteria:

• History of clinically relevant impaired endocrine, thyroid, hepatic, respiratory or renal function, uncontrolled hypertension, diabetes mellitus, coronary heart disease, or psychotic mental illness.

• History of any clotting disorder, including predisposition to hypercoagulation or any previous thromboembolic event.

• Elevations in blood pressure, based on criteria provided in Section 7.2.3. OR Subjects with a blood pressure >140/90 mmHg, at screening.

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

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• A positive pre-study drug/alcohol screen.

• A positive test for HIV antibody.

• History of regular alcohol consumption within 6 months of the study defined as: For US sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

• 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 prohibited medications as described in Section 9.2.

• 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.

• 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.

• 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 from 7 days prior to the first dose of study medication.

• Any prior intraocular surgery, excluding cataract surgery (Part 2 only)

• Any prior eye surgery within three months to first dose of study medication (Part 2 only).