Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Dose-finding Study Evaluating the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura (ITP)
Brief Summary: The primary objective of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with ITP.


Options:
A: Inclusion criteria:

* Patients with chronic low platelet count (less than 30,000/µL) for 6 months who have failed at least one treatment for chronic low platelet count.
* Patients receiving chronic maintenance steroid therapy must have received a stable dose for at least 1 month.
* Normal PT and PTT.

Exclusion criteria:

* History of clotting disorder.
* Females who are pregnant or are receiving hormone replacement therapy or systemic contraceptives.
* History of alcohol/drug abuse or dependence within 1 year.
* Use of aspirin, aspirin-containing compounds, salicylates, antacids, rosuvastatin, pravastatin, non-steroidal anti-inflammatory drugs during the study and within 3 weeks prior to starting the study.
* History of HIV infection or active infection with Hepatitis B or C.
B: Inclusion Criteria:

* Subject is ≥ 18 years of age
* Subject has a diagnosis of Idiopathic Thrombocytopenia Purpura (ITP) according to the American Society of Hematology (ASH) guidelines
* If subject is \> 60 years of age, subject has a written bone marrow biopsy report confirming the diagnosis of ITP
* Subject has received at least 1 prior therapy for ITP
* Subject has a platelet count \< 50,000 or their platelet count falls to \< 50,000 during or after a clinically-indicated taper or discontinuation of current ITP therapy
* Before any study-specific procedure, the appropriate written informed consent must be obtained

Exclusion Criteria:

* Subject has had a splenectomy for any reason
* Subject has an active malignancy
* Subject has a history of cancer, other than basal cell carcinoma or cervical carcinoma in situ, with treatment or active disease within 5 years
* Subject has a known history of bone marrow stem cell disorder
* Subject has participated in any study evaluating polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO), AMG 531, or a thrombopoietic protein
* Subject is receiving other investigational agents or procedures
* Subject is currently enrolled in, or has completed within the last 30 days, another investigational device or drug study
* Subject is pregnant or breast feeding
* Subject is not using adequate contraceptive precautions
* Subject has known sensitivity to any recombinant E. coli-derived product
* Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative
* Subject has any kind of disorder that compromises the ability of the subject to comply with study procedures
C: Inclusion criteria:

* A subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Subject has signed and dated a written informed consent.
* Adults (≥18 years) diagnosed with chronic ITP according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines \[George, 1996; BCSH, 2003\], and platelet count \< 30,000/μL on Day 1 (or within 24 hours prior to dosing on Day 1). In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia (e.g. pseudothrombocytopenia, myelofibrosis). The physical examination should not suggest any disease which may cause thrombocytopenia other than ITP.
* Subjects who have previously received one or more prior ITP therapies. Previous treatments 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 a previous 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 been completed at least 1 week prior to randomization and the platelet count must show a clear downward trend after the last treatment with immunoglobulins. Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to randomization, or clearly be ineffective.
* Subjects treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior to randomization. Subjects treated with cyclosporine A, mycophenolate mofetil or danazol must be receiving a dose that has been stable for at least 3 months prior to randomization. The medication should be continued with a stable dose for the initial 6 weeks of study "Concomitant ITP Therapy")
* Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range with no history of hypercoagulable state.
* A complete blood count (CBC), within the reference range (including WBC differential not 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 for inclusion,
* Hemoglobin: Subjects with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit 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 to steroid 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 alkaline phosphatase. 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 of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal \> 1 year), or of childbearing potential and use one of the following highly effective methods of contraception (i.e., Pearl Index \<1.0%) from two weeks prior to administration of study medication, throughout the study, and 28 days after 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 condom plus spermicide);
* Male partner is sterile prior to entry into the study and is the only partner of the female;
* Systemic contraceptives (combined or progesterone only). Subject is able to understand and comply with protocol requirements and instructions and intends to complete the study as planned.

Exclusion criteria:

* A subject will NOT be eligible for inclusion in this study if any of the following criteria apply:
* Any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
* Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy 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 the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, etc), or any other family history of arterial or venous thrombosis.
* Pre-existing cardiovascular disease (congestive heart failure, New York Heart Association \[NYHA\] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic 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 chorionic gonadotrophin 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 is longer) preceding the first dose of study medication.
* Subject treated with drugs that affect platelet function (including but not limited to aspirin, 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 of platelet counts.
* All subjects with secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence for active hepatitis at the time of subject screening. If a potential subject has no clinical history that would support HIV infection or hepatitis infection, no further laboratory screening is necessary; however, standard medical practice would suggest further evaluation 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 security category.
D: Inclusion Criteria:

* Diagnosis of ITP according to American Society of Hematology (ASH) guidelines at least 3 months before enrollment
* Have completed at least 1 prior treatment for ITP
* Two (including day -2) of the 3 platelet counts taken during the screening and pre-treatment periods must have fulfilled the following:

  * less than 30 x 10\^9/L for those subjects not receiving any ITP therapy,
  * less than 50 x 10\^9/L for those subjects receiving any ITP therapy
* Eastern Cooperative Oncology Group performance status of 0 to 2
* Serum creatinine concentration ≤ 2 mg/dL (≤ 176.8 µmol/L)
* Adequate liver function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range
* Hemoglobin greater than 10.0 g/dL
* Written informed consent

Exclusion Criteria:

* Considered a substantial risk for adverse outcomes because of a clinically important trend (as determined by the investigator) detected in the platelet counts during the screening period
* Any known history of bone marrow stem cell disorder
* Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization
* Documented diagnosis of arterial thrombosis (ie, stroke, transient ischemic attack, or myocardial infarction) in the previous year; history of venous thrombosis (ie, deep vein thrombosis, pulmonary embolism) and receiving anticoagulation therapy
* Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure \[New York Heart Association (NYHA) greater than class II\], uncontrolled hypertension \[diastolic greater than 100 mmHg\] or cardiac arrhythmia)
* Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker using oral contraceptives; hypercholesteremia (\> 240 mg/dL); treatment for hypertension
* Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus
* Received any treatment for ITP (except for a constant dose schedule of corticosteroids) within 4 weeks before the screening visit
* Received intravenous (IV) immunoglobulin (Ig) or WinRho within 2 weeks before the screening visit
* Received hematopoietic growth factors, including interleukin (IL)-11 (Neumega®) within 4 weeks before the screening visit
* Past or present participation in any study evaluating polyethylene glycol recombinant human magakaryopoiesis differentiating factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO), or related platelet product
* Received any alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
* Received any monoclonal antibody (eg, rituximab) within 16 weeks before the screening visit or anticipated use during the time of the proposed study
* Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period
* Less than 2 months since major surgery (including laparoscopic splenectomy)
* Pregnant or breast feeding
* Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator

Answer: D