Official Title: “A Phase I, Double-Blind, Placebo and Observer-Blind Positive Controlled, Randomized, Parallel Group Study in Healthy Subjects to Investigate the Photoirritant Potential of Eltrombopag”

This study is designed to investigate the safety profile and the photoirritant potential of eltrombopag in healthy subjects. The study is placebo- and positive controlled, randomized, parallel group with three treatment arms: eltrombopag (75 mg QD), placebo, and a positive control (ciprofloxacin, 500 mg BID). Eltrombopag will be administered in a double-blind fashion with respect to placebo and the positive control, ciprofloxacin, will be administered under observer-blinded conditions. Twelve to fifteen subjects will be recruited into each arm, to assure total enrollment of 36 evaluable subjects. The primary endpoint is the photosensitizing potential of eltrombopag as measured by photoirritant index (PI) and change in minimum erythemal dose (MED) in comparison with placebo.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety Study

Study Primary Completion Date: July 2008

Intervention(s) in this Clinical Trial

• Drug: Ciprofloxacin
• Drug: Eltrombopag

Primary Measures

• Evaluate the photosensitizing potential, as measured by photoirritant index and change from baseline in minimum erythemal dose, of eltrombopag when dosed orally at 75 mg QD as compared to placebo and ciprofloxacin 500 mg BID.

Secondary Measures

• Severity of phototoxic response Concentration of porphyrins, ANF, anti-Ro, and anti-La as measured on Day 6.
  • Time Frame: Day 6
    
• Vital signs (blood pressure, heart rate, respiration rate and body temperature) taken after resting semi-supine position for at least 10 minutes;
• Clinical laboratory tests
• Assessment of AEs.

Inclusion Criteria:

• Healthy Caucasian male or females with no clinically significant abnormality identified by the physician by evaluation of medical history, physical examination, clinical laboratory tests or 12-lead ECG.
• Age 18 to 65 years, inclusive.
• Female who is neither pregnant nor lactating, and is of non-childbearing potential or child-bearing potential with negative βhCG test and agrees to comply with recognized non-hormonal contraceptive methods
• Body weight >/50 kg and BMI within the range 19-29.9 kg/m2.
• Capable of giving written informed consent.
• Skin Type 1, 2, or 3 according to protocol criteria
• Negative test for porphyrins, ANF, anti-Ro and anti-La at screening.
• Liver function tests that are within the reference range, or deviations that are not considered clinically significant at screening by the investigator.
• Baseline MED within the normal range
• Able to understand and comply with protocol requirements and time tables, instructions and protocol-stated restrictions.

Exclusion Criteria:

• Any clinically relevant abnormality identified on the screening history, physical or laboratory examination, or 12-lead ECG.
• Any sun or sunbed exposure to the skin of the back during the four weeks prior to the screening period.
• History of polymorphic light eruption.
• History of previously severe photosensitivity to ciprofloxacin, any of the study medications or components thereof.
• History of malignant melanoma in a first degree family member.
• History of Gilbert Syndrome.
• History of deep vein thrombosis or any other thromboembolic event.
• History of sensitivity to heparin, or heparin-induced thrombocytopenia.
• History of platelet clumping that prevents reliable measurement of platelet counts.
• History of thrombocytopenia or bleeding due to abnormal platelet number or function.
• C-reactive protein (CRP) that is elevated above normal range and considered clinically significant at screening.
• History of myocardial infarction, stroke or sudden unexplained death in a first degree family member under the age of 60 years.
• Clotting factor abnormalities associated with hypercoagulability.
• Hemoglobin, white blood cells, platelet count or reticulocyte count that are outside the reference range and considered clinically significant at screening by the investigator.
• Positive test for HIV, hepatitis B virus or hepatitis C virus.
• Positive urine drug screen including alcohol.
• History of alcohol/drug abuse or dependence within 12 months of screening.
• History of regular alcohol consumption exceeding average weekly intake of greater than 21 units or an average daily intake of greater than three units (males) or an average weekly intake of greater than 14 units or an average daily intake of greater than two units (females). .
• Cannot refrain from smoking during the study period from Day-1 through the completion of follow-up assessments.
• Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
• 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 aspirin and NSAIDs), vitamins, herbal and dietary supplements, or any herbal remedies containing St. John's
• Wort within seven days (or 14 days if the drug is a potential enzyme inducer) or five half-lives (whichever is longer) prior to the first dose of study medication and through the completion of follow-up assessments. By exception, acetaminophen (or, paracetamol) at doses of </2 g/day and stable thyroid replacement therapy will be allowed.
• Consumption of antacids (e.g., Maalox, Mylanta, Amphogel, Milk of Magnesia or TUMS™) within 48 hrs of the first dose of study medication and until the completion of follow-up assessments.
• Clinically significant skin/allergic disease, including photo-allergy (excluding non-active hay fever).
• Tattoos that may obscure skin reactions or that restrict the skin surface area available for testing.
• Consumption of grapefruit, pomelo or Seville oranges from screening until the completion of follow-up assessments.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: GlaxoSmithKline

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, MD Study Chair GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00688272

Study ID Number: TRA106914

ClinicalTrials.gov Identifier: NCT00688272

Health Authority: United States: Food and Drug Administration