RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag

Inclusion criteria:

• A subject will be eligible for inclusion in this study only if all of the followingcriteria apply:

• Subject has signed and dated a written informed consent.

• Adults (≥18 years) diagnosed with chronic ITP according to the American Society forHematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003], and platelet count < 30,000/μL on Day 1 (or within 24hours prior to dosing on Day 1). In addition, a peripheral blood smear should supportthe diagnosis of ITP with no evidence of other causes of thrombocytopenia (e.g.pseudothrombocytopenia, myelofibrosis). The physical examination should not suggestany disease which may cause thrombocytopenia other than ITP.

• Subjects who have previously received one or more prior ITP therapies. Previoustreatments for ITP include but are not limited to corticosteroids, immunoglobulins,azathioprine, danazol, cyclophosphamide and/or rituximab.

• Subjects must have either initially responded (platelet count > 100,000/μL) to aprevious ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndromes or other causes of thrombocytopenia.

• Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have beencompleted at least 1 week prior to randomization and the platelet count must show aclear downward trend after the last treatment with immunoglobulins. Previous treatmentfor ITP with splenectomy, rituximab and cyclophosphamide must have been completed atleast 4 weeks prior to randomization, or clearly be ineffective.

• Subjects treated with concomitant ITP medication (e.g. corticosteroids orazathioprine) must be receiving a dose that has been stable for at least 4 weeks priorto randomization. Subjects treated with cyclosporine A, mycophenolate mofetil ordanazol must be receiving a dose that has been stable for at least 3 months prior torandomization. The medication should be continued with a stable dose for the initial 6weeks of study "Concomitant ITP Therapy")

• Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must bewithin 80 to 120% of the normal range with no history of hypercoagulable state.

• A complete blood count (CBC), within the reference range (including WBC differentialnot indicative of a disorder other than ITP), with the following exceptions:

• < 30,000 platelets/μL on Day 1 (or within 24 hours of Day 1) is required forinclusion,

• Hemoglobin: Subjects with hemoglobin levels between 10 g/dL (100 g/L) and the lowerlimit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).

• ANC ≥ 1500/μL (1.5 x 10^9/L) is required for inclusion (elevated WBC/ANC due tosteroid treatment is acceptable).

• The following clinical chemistries MUST NOT exceed the upper limit of normal (ULN)reference range by more than 20%: creatinine, ALT, AST, total bilirubin, and alkalinephosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.

• Subject is practicing an acceptable method of contraception (documented in chart).Female subjects (or female partners of male subjects) must either be ofnon-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tuballigation or post-menopausal > 1 year), or of childbearing potential and use one of thefollowing highly effective methods of contraception (i.e., Pearl Index <1.0%) from twoweeks prior to administration of study medication, throughout the study, and 28 daysafter completion or premature discontinuation from the study:

• Complete abstinence from intercourse;

• Intrauterine device (IUD);

• Two forms of barrier contraception (diaphragm plus spermicide, and for males condomplus spermicide);

• Male partner is sterile prior to entry into the study and is the only partner of thefemale;

• Systemic contraceptives (combined or progesterone only). Subject is able to understandand comply with protocol requirements and instructions and intends to complete thestudy as planned.

Exclusion criteria:

• A subject will NOT be eligible for inclusion in this study if any of the followingcriteria apply:

• Any clinically relevant abnormality, other than ITP, identified on the screeningexamination or any other medical condition or circumstance, which in the opinion ofthe investigator makes the subject unsuitable for participation in the study orsuggests another primary diagnosis (e.g., thrombocytopenia is secondary to anotherdisease).

• Concurrent malignant disease and/or history of cancer treatment with cytotoxicchemotherapy and/or radiotherapy.

• Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack,myocardial infarction, deep vein thrombosis or pulmonary embolism), AND ≥ two of thefollowing risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication forhypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIIIdeficiency, etc), or any other family history of arterial or venous thrombosis.

• Pre-existing cardiovascular disease (congestive heart failure, New York HeartAssociation [NYHA] Grade III/IV), or arrhythmia known to increase the risk ofthromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec.

• Female subjects who are nursing or pregnant (positive serum or urine b-human chorionicgonadotrophin pregnancy test) at screening or pre-dose on Day 1.

• History of alcohol/drug abuse.

• Treatment with an investigational drug within 30 days or five half-lives (whichever islonger) preceding the first dose of study medication.

• Subject treated with drugs that affect platelet function (including but not limited toaspirin, clopidogrel and/or NSAIDs) or anti-coagulants for > 3 consecutive days within 2 weeks of the study start and until the end of the study.

• History of platelet agglutination abnormality that prevents reliable measurement ofplatelet counts.

• All subjects with secondary immune thrombocytopenia, including those with laboratoryor clinical evidence of HIV infection, anti-phospholipid antibody syndrome, chronichepatitis B infection, hepatitis C virus infection, or any evidence for activehepatitis at the time of subject screening. If a potential subject has no clinicalhistory that would support HIV infection or hepatitis infection, no further laboratoryscreening is necessary; however, standard medical practice would suggest furtherevaluation of patients who have risk factors for these infections.

• Previous participation in a clinical study with eltrombopag.

• Patients planning to have cataract surgery.

• In France, a subject is neither affiliated with nor a beneficiary of a social securitycategory.