Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Open-label, Five-period, Balanced Crossover Study to Evaluate the Relative Bioavailability of an Eltrombopag Powder for Oral Suspension (PfOS) Formulation Relative to the Commercial 25 mg Tablet Formulation and to Evaluate Administration of the PfOS Formulation With and Separated 2 Hours From a High Calcium Meal in Healthy Adult Subjects
Brief Summary: This is a randomized, open-label, five-period, balanced crossover study conducted in approximately 40 healthy adult subjects enrolled at one study center in the USA. Subjects receive five eltrombopag treatments: tablet fasted, Powder for Oral Suspension (PfOS) fasted, PfOS with a high calcium meal, PfOS 2 hours prior to a high calcium meal, and PfOS 2 hours after a high calcium meal, and each treatment is a single 25 mg dose. There is a 10 to 14 day washout between periods, and between the last dose of study drug and the follow-up visit. During each treatment period, subjects undergo serial PK sampling over 72 hours for measurement of plasma eltrombopag concentrations. Safety is assessed by vital signs, clinical safety laboratory assessments, and adverse events reporting.


Options:
A: Inclusion criteria:

* Subjects ≥18 years old, who are chemotherapy naïve, with histologically or cytologically confirmed advanced solid tumor (leukemia and lymphoma are excluded) who are scheduled to received carboplatin/paclitaxel as shown below. For the purpose of this study, advanced tumors are defined as tumors that are being treated with palliative intent (i.e., not being treated with curative intent).
* Subjects scheduled to receive first-line chemotherapy as carboplatin AUC 5-6 IV over 30 minutes plus paclitaxel 175-225 mg/m2 IV over 3 hours on day 1 every 21 days, with routine pre-medications, i.e., 20 mg dexamethasone \[or equivalent\] orally 6 and 12 hours pre-paclitaxel, 50 mg IV diphenhydramine \[or equivalent\] and 300 mg IV cimetidine \[or equivalent\] 30-60 minutes pre-paclitaxel.
* ECOG-Zubrod performance status is 0, or 1.
* Subject has no history of platelet disorders or dysfunction and no history of a bleeding disorder.
* Subjects have adequate:

hematologic function (ANC ≥ 1,500/mm3, hemoglobin ≥ 9 g/dL, and platelet count ≥100,000/mm3 and \< upper limit of normal range (eg, 400,000 to 450,000/mm3), hepatic function (bilirubin ≤ 2 mg/dL and alanine aminotransferase ≤ three times the upper limit of normal), renal function (creatinine ≤ 2.0 mg/dL).

* Subject has no physical limitation to ingest and retain oral medication.
* Subject has life expectancy of at least 6 months.
* Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of nonchildbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal \> 1 year), or of childbearing potential and use one of the following acceptable methods of contraception 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 intend to complete the study as planned.
* Subject has signed and dated written informed consent.
* Chemotherapy naive patients with advanced solid tumors (without brain metastasis or rapid progression within 2 weeks) who are scheduled to receive standard first-line therapy with carboplatin and paclitaxel every 21 days.
* Adequate hematologic, hepatic and renal function.

Exclusion criteria:

* Any clinically relevant abnormality, other than cancer, 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 and/or would make the patient's data difficult to interpret.
* Subjects with a known history of rapidly progressive disease (marked increase in tumor size \[\>50%\], ascites, or serious symptoms related to underlying cancer in the preceding 4-week period), surgery within the previous 2 weeks, radiotherapy within the previous 4 weeks, or any prior chemotherapy.
* Subjects with known pre-existing cardiac disease, including congestive heart failure, arrhythmias requiring treatment, or myocardial infarction within the preceding 3 months.
* Subjects with abnormal resting 12-lead ECG at screening that would indicate preexisting cardiac disease, as noted in exclusion criterion 3.
* Subjects with known clotting disorder associated with hypercoaguability.
* Subject has consumed aspirin, aspirin-containing compounds, salicylates, quinine or non-steroidal anti-inflammatories (NSAIDs) for \> 3 consecutive days within 2 weeks of the study start and would require them at any time during the study.
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
* Subject has consumed liquid antacids (e.g. Maalox, Mylanta, Amphogel, milk of magnesia), chewable antacids (e.g. TUMS) or calcium supplements within 48 hours of the first dose of study medication, and/or will require these medications during the study.
* Subject has consumed rosuvastatin or pravastatin within 1 week of the first dose of study medication and/or will require these medications at any time during the study.
* Any history of drug-induced thrombocytopenia (e.g., quinine).
* Systemic anti-coagulant use within 4 weeks prior to study entry.
* Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements (See Exclusion 8 for calcium supplements), within 1 week of the study start.
* Female subjects who are lactating or have a positive beta-hCG at screening.
* Subjects with a history of CNS metastases or clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan.
* History of platelet or bleeding disorders.
* Patients using aspirin, aspirin-containing compounds, salicylates, antacids, rosuvastatin, pravastatin, non-steroidal anti-inflammatory drugs for greater than 3 days during and within 3 weeks prior to the study.
* Females who are pregnant or breastfeeding.
B: Inclusion Criteria:

* Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification
* Low or Intermediate-1 risk category MDS using the IPSS
* Planned to receive lenalidomide 10 mg capsule by mouth daily for all 28 days of each cycle for at least 4 cycles
* Eastern Cooperative Oncology (ECOG) performance status of 0-2
* Subjects must be at least 18 years of age or older

Exclusion Criteria:

* Prior exposure to \>3 cycles of lenalidomide
* Exposure to lenalidomide within the last 30 days
* Prior history of leukemia or aplastic anemia
* Prior history of stem cell transplantation
* Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for 3 years before randomization
* Active or uncontrolled infections
* Unstable angina, congestive heart failure \[NYHA \> class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
* History of arterial thrombosis ( eg, stroke or transient ischemic attack) in the past year
* History of venous thrombosis in the past year
* Received IL-11 within 4 weeks of screening
* Less than 4 weeks since receipt of any investigational drug or device
* Have previously received any other thrombopoietic growth factor
* Pregnant or breast feeding
* Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
* Known hypersensitivity to any recombinant E coli-derived product
C: Inclusion Criteria:

* Diagnosis of MDS using the World Health Organization classification
* Low or Intermediate-1 risk MDS using the International Prognostic Scoring System (IPSS)
* The mean of two platelet counts taken during the screening period must be ≤ 50 x 10\^9/L, with no individual count \> 55 x 10\^9/L (The mean platelet counts of 5 subjects enrolled at the maximum tolerated dose (MTD) must be ≤ 20 x 10\^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1.
* Must be ≥ 18 years of age at the time of obtaining informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening
* Adequate Liver Function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), alanine aminotransferase (ALT) ≤ 3 times the laboratory normal range, and aspartate aminotransferase (AST) ≤ 3 times the laboratory normal range
* A serum creatinine concentration ≤ 2 mg/dL (≤ 176.6 µmol/L)
* Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1)

Exclusion Criteria:

* Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1
* Clinically significant bleeding within 2 weeks prior to screening (eg, gastrointestinal (GI) bleeds, intracranial hemorrhage)
* Prior malignancy (other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years before screening
* Prior history of bone marrow transplantation
* Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count \> 1,000/µL)
* Unstable angina, congestive heart failure (New York Heart Association \[NYHA\] \> class II), uncontrolled hypertension (diastolic \> 100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
* Received Anti-Thymocyte Globuline (ATG) within 6 months of screening
* Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening
* Received interleukin (IL)-11 (oprelvekin) within 4 weeks before screening
* Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating factor \[G-CSF; Neupogen, Granocyte\], pegfilgrastim \[Neulasta\], granulocyte macrophage-colony stimulating factor \[GM-CSF; Leukine, Prokine, Sargramostim\])
* Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or romiplostim
* Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and Drug Administration (FDA) approved for any indication
* Other investigational procedures are excluded
* History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year
* History of venous thrombosis that currently requires anti-coagulation therapy
* Untreated B12 or folate deficiency
* Subject is evidently pregnant (eg, positive human chorionic gonadotropin \[HCG\] test) or is breast feeding
* Subject is not using adequate contraceptive precautions
* Subject has known hypersensitivity to any recombinant E coli-derived product
* Subject previously has enrolled in this study
* Subject will not be available for follow-up assessment
* Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
D: Inclusion Criteria:

1. Healthy subjects with no clinically significant abnormality identified by physician by evaluation of medical history, physical examination, clinical laboratory tests or electrocardiogram (ECG).
2. Male and female subjects between the ages of 18 to 64 years of age inclusive, at the time of signing the informed consent.
3. Subject is able to understand and comply with the protocol requirements, instructions and restrictions.
4. Capable of giving written informed consent which includes compliance with the requirements and restrictions listed in the consent form.
5. Body weight ≥ 50kg (110 lbs) for men and ≥ 45 kg (99 lbs) for women and body mass index (BMI) of 18.5 to 29.9 kg/m2 inclusive.
6. A platelet count within normal range and not \> 400,000 plt/uL.
7. Male subjects, who are not surgically sterile, must agree on abstinence or to use a double barrier method, such as, a condom plus spermicidal agent (foam/gel/film/cream/suppository). This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of medication.
8. A female subject is eligible to participate if she is neither pregnant nor lactating, and falls into one of the following categories:

   * non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or bilateral oophorectomy, or post-menopausal females defined as being amenorrheic for greater than one year and having serum estradiol and follicle stimulating hormone levels consistent with menopause.
   * child-bearing potential with negative beta human chorionic gonadotropin (beta/hCG) test and agrees to comply with recognized non-hormonal contraceptive methods from screening or at least two weeks prior to first dose (whichever is earlier) until the follow-up visit. Recognized non-hormonal contraceptive methods include: complete abstinence from intercourse, male partner sterilization, two forms of barrier contraception (e.g. condom and occlusive cap (diaphragm or cervical/vault caps with spermicide), or intrauterine device (IUD), or intrauterine system (IUS) with a \< 1% failure rate stated in the product label.

Exclusion Criteria:

1. History of Gilbert's syndrome.
2. Any previous history of deep vein thrombosis or any other thromboembolic event.
3. History of thrombocytopenia or bleeding due to abnormal platelet number or function.
4. Clotting factor abnormalities associated with hypercoagulability, specifically Factor V Leiden, Protein C or Protein S deficiency or antithrombin III deficiency.
5. Elevated blood pressure (BP) at screening (systolic \> 140 mm Hg, diastolic \> 85 mm Hg). If the subject's BP is elevated on the first measurement, complete two additional BP measurements two minutes apart and average the three assessments to evaluate this criteria. If averaged BP exceeds the safety criteria, the subject should be excluded.
6. History of atrial fibrillation, mitral valve prolapse, significant heart murmur or vascular bruit.
7. Prolonged QTc interval (Bazett's) at screening (for females \> 450 msec and for males \> 430 msec). If the QTc interval is prolonged on the initial ECG, then complete two additional ECGs 5 minutes apart and take the average QTc measurements of all three ECGs to evaluate this criteria. If averaged QTc exceeds the safety criteria, the subject should be excluded.
8. Female subjects currently receiving hormone replacement therapy (HRT).
9. Positive for HIV, hepatitis B virus or hepatitis C virus assays at screening.
10. Positive urine drug screen including alcohol at screening or pre-dose (Day -1).
11. History of alcohol/drug abuse or dependence within 12 months of the study.
12. History of alcohol consumption in the past six months exceeding 7 units/week for women and 14 units/week for men (where 1 unit = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).
13. Urinary cotinine levels indicative of smoking at screening or pre-dose (Day -1). History of regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
14. Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
15. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
16. Use of prescription or non-prescription drugs (including aspirin and non-steroidal anti-inflammatory drugs \[NSAIDs\]), vitamins, herbal and dietary supplements within seven days (or 14 days if the drug is a potential enzyme inducer, such as St. John's Wort) or five half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
17. Subjects who have donated plasma within seven days prior to the screening visit or where participation in this study would result in donation of blood in excess of 500 mL within a 56-day period.
18. History of sensitivity to any of the study medications, or components thereof.

Answer: D