Primary Outcome Measures:
- Change in baseline platelet count from the first day of the second cycle of chemotherapy to the lowest count observed (nadir) during the cycle(21 days) [ Time Frame: throughout entire study ]
Secondary Outcome Measures:
- Safety and tolerability, pharmacodynamics, changes in platelet count during cycle 1(21 days) and beyond cycle 2(21 days), population PK, and deliver
intended doses of chemotherapy without thrombocytopenia related AEs [ Time Frame: Throughout entire study ]
- Safety and tolerability as indicated by physical exam, 12-lead ECGs, ophthalmologic examinations, clinical laboratory tests, clinical
monitoring/observation, and AE reporting
- Pharmacodynamic parameters including platelet count, grade of thrombocytopenia,
serum thrombopoietin, and platelet aggregation/activation during the first and second cycles of carboplatin/paclitaxel
- Change in platelet count from day 1 (baseline) to nadir during the first cycle and beyond the second cycle of carboplatin/paclitaxel
- Population PK of SB-497115, including clearance (CL/F), absorption rate constant
(ka), and volume of distribution (V/F) with assessment of demographic covariates influencing SB-497115 PK
- The relationship between PK of SB-497115 and
relevant safety and efficacy endpoints will be explored
- Dose intensity (percent of intended dose) of carboplatin/paclitaxel
- Carboplatin/paclitaxel-associated thrombocytopenia-related AEs, as defined by NCI
- Common Terminology Criteria for Adverse Events, CTCAE v3.0, to include the
number of platelet transfusions, bleeding events (hematoma), hemorrhage/bleeding,
petechiae/purpura), clinical laboratory tests, and clinical observations
A Double-Blind, Randomized, Multicenter, Placebo-Controlled, Parallel Group, Dose Ranging Study to Assess the Efficacy, Safety, and Pharmacokinetics of an Oral Thrombopoietin Receptor Agonist (SB-497115-GR) Administered at 50, 75, and 100 mg to Cancer Patients Receiving Multiple Cycles of Chemotherapy