Clincosm LogoSign in Get a demo

Safety and Efficacy Study for Solid Tumor Patients Treated With Eltrombopag

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01147809
Collaborator
(none)
130
Enrollment
86
Locations
2
Arms
57
Duration (Months)
1.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The present study is a randomized, blinded, placebo-controlled, two-Phase, sequential cohort, dose finding study to assess the safety and efficacy of eltrombopag in patients with solid tumors receiving gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin. Phase I of the study will examine safety and tolerability of various doses of eltrombopag to identify a dose and schedule of eltrombopag. Phase II will confirm that the chosen dose and schedule of eltrombopag from Phase I can deliver clinically meaningful benefit(s) to thrombocytopenic patients by improving platelet numbers.

Condition or Disease Intervention/Treatment Phase
  • Drug: Eltrombopag olamine
  • Other: Placebo
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
130 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
Official Title:
A Randomized, Blinded, Placebo-controlled, Two-Phase, Sequential Cohort, Dose Finding Study to Assess the Safety and Efficacy of an Oral Thrombopoietin Receptor Agonist, Eltrombopag (SB-497115-GR), Administered to Patients With Solid Tumors Receiving Gemcitabine Monotherapy or the Combination of Gemcitabine Plus Carboplatin or Cisplatin
Study Start Date :
Jun 1, 2010
Actual Primary Completion Date :
Jan 1, 2015
Actual Study Completion Date :
Mar 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Eltrombopag

Drug: eltrombopag olamine thrombopoietin receptor agonist

Drug: Eltrombopag olamine
thrombopoietin receptor agonist
Placebo Comparator: Placebo

Other: Placebo Placebo tablets with no active pharmaceutical ingredient

Other: Placebo
Placebo tablets with no active pharmaceutical ingredient

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase I [From Cycle 1, Day 1 (C1D1) until at least 30 days post-investigational product discontinuation (longer for AEs considered related to study participation)]

    AEs are coded using the standard Medical Dictionary for Regulatory Activities (MedDRA) and were graded by the investigator according to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), version 4.0. AE is any untoward medical occurrence temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a MP. For marketed MPs, this also includes failure to produce expected benefits, abuse, or misuse. SAE event is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect.

  2. Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Hematology Parameters, at Anytime Post-Baseline in Phase I [After Baseline (C1D1), on-treatment and 30 day follow-up]

    Hematology parameters with a related NCI CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment, the maximum toxicity grade reached by a participant post-Baseline was summarized. Hematology parameters included hemoglobin (increased), hemoglobin (anemia), lymphocytes (increased), lymphocytes (decreased), total absolute neutrophil count (ANC), platelets (PLT) and white blood cells (WBC). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. Only those participant available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).

  3. Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Clinical Chemistry Laboratory Parameters, at Anytime Post-Baseline in Phase I [After Baseline (C1D1), on-treatment and 30 day follow-up]

    Clinical chemistry laboratory parameters with a related NCI CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment. Clinical chemistry laboratory parameters included albumin (Alb), urea/blood urea nitrogen (BUN), creatinine, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), direct bilirubin (DB) and international normalized ratio/Prothrombin time (PT). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. Only those participants available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).

  4. Number of Participants With a Change From Baseline in Creatinine of >=26.5 Micromoles/Liter (UMOL/L) in Phase I [After Baseline (C1D1), on-treatment and 30 day follow-up]

    The number of participants with at least 1 change from Baseline in creatinine, with an increase >=26.5 UMOL/L are reported. Creatinine clearance is estimated using the Cockcroft-Gault formula which is a method to approximate kidney function. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1.

  5. Number of the Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Scores at the Indicated Time Points in Phase I [Screening, C1D1, C2D1, C2D8, C2D15, C3D1, C4D1, C4D22, C5D1, C5D8, C6D1, C6D15]

    ECOG-Zubrod scores for the performance status are defined as follows: Score 0: Fully active, 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2: ambulatory and capable of all self-care but unable to carry out any work activities, 3: capable of only limited self-care, 4: completely disabled, 5: dead. The data is presented for the participants with the ECOG performance score at the indicated time points during the study.

  6. Number of Participants With Electrocardiogram (ECG) Findings at Anytime Post-Baseline in Phase I [C2D4, C2D8, C5D8, C6D15]

    A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at screening and post-dose on C2D4. Three further ECGs were carried out at C2D8, C5D8 and C6D15. Change in ECG findings were categorized as 'Clinically significant change: favorable', 'No change or insignificant change' or 'Clinically significant change (CSC): unfavorable' as determined by the investigator. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Any time post-Baseline is defined by counting the participants under the worst result experienced post-Baseline. The best to worst order is 'Clinically significant change: favorable', 'No change or insignificant change', and then 'Clinically significant change (CSC): unfavorable. Only those participants available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).

  7. Mean Day 1 Scheduled Pre-chemotherapy Platelet Count Evaluated Across Cycles 1 to 6 in Phase II [Day 1 (averaged across cycles 1 to 6)]

    Scheduled pre-chemotherapy platelet count is defined within each cycle as the platelet count assessment on which the decision to give or delay chemotherapy was made. This was averaged for each participant across Cycles 1 to 6 and a natural log transformation was applied to the average. The log-transformed values were compared between eltrombopag and placebo groups using an analysis of covariance (ANCOVA) model adjusting for cycle duration (21-day vs. 28-day), Baseline loge(platelet count) and part of study (part 1 or 2 of phase II). Only those participants available at indicated time points were analyzed (represented by n=X,X).

Secondary Outcome Measures

  1. Average Pre-chemotherapy Platelet Count at the Indicated Time Points in Phase I [C1D1, C1D8, C1D15, C2D1, C2D8, C2D15, C3D1, C3D8, C3D15, C4D1,C4D8, C4D15, C5D1,C5D8, C5D15, C6D1,C6D8 and C6D15]

    Pre-chemotherapy platelet count is defined for Cycle 1 as the platelet count (from central laboratory data) immediately preceding the first dose of chemotherapy within Cycle 1. For all subsequent cycles it is defined as the platelet count (from central laboratory data) immediately preceding, but limited to within 2 days prior to the first dose of chemotherapy at Day 1. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet count at the following time points: Group A; Days 1 and 8 of Cycles 1 to 6. Group B; Days 1, 8 and 15 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).

  2. Average Within-subject Central Laboratory Platelet Count Prior to Scheduled Chemotherapy Across Cycles 2 to 6 in Phase I [Day 1 (averaged across Cycles 2 to 6), Day 8 (averaged across Cycles 2 to 6)]

    Within-subject platelet count for each participant was calculated by summing up the visit platelet counts from each of Cycles 1 to 6 and dividing it by the number of cycles in which the participant had data. The average within a treatment group was calculated by summing up the values from each participant within the treatment group and dividing it by the number of participants. These platelet counts are different from the pre-chemotherapy platelet counts for cycles where the chemotherapy dose was delayed. Average within-subject central laboratory platelet count prior to scheduled chemotherapy across Cycles 2 to 6 are summarized. Blood samples were collected on Days 1 and 8 of Cycles 2 to 6 for Group A and on Days 1, 8 and 15 from Cycles 2 to 6 for Group B to estimate the average within subject platelet count prior to scheduled chemotherapy. Only those participants available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).

  3. Platelet Count Nadir for Each Chemotherapy Cycle in Phase I [Cycle 1 to Cycle 6]

    Platelet nadir is defined as the lowest platelet count (from central laboratory data) reported after the first dose of chemotherapy within each cycle. Platelet count nadir is defined for each cycle. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet nadir count at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 and 2, at Days 1, 4, 8, 15 and 17 of Cycle 3 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).

  4. Central Laboratory Average Daily Area Under the Curve Platelet-time Course Across Cycles 2 to 6 in Phase I [All assessments from Cycle 2 Day 1 to last assessment in Cycle 6]

    The average daily area under the platelet-time course was normalized by dividing the area under curve by total duration. This gives an estimated average platelet value over the time period from cycles 2 to 6. For 21-Day Cycle, the chemotherapy cycle consisted of 21 days and for 28-Day Cycle, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate thrombocytes at the following time points: 21-Day Cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-Day Cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6.

  5. Number of Participants With Thrombocytopenia of Grade 1, 2, 3 or 4 Across All the Chemotherapy Cycles in Phase I, Using Central Laboratory Platelet Count [Cycle 1 to Cycle 6]

    As per the CTCAE version 4.0, par. with a platelet count <LLN but >=75 x 10^9/L (Gi/L) were considered to have Grade 1 thrombocytopenia; par. with a platelet count <75Gi/L, but >=50Gi/L were considered to have Grade 2 thrombocytopenia; par. with a platelet count <50Gi/L, but >=25Gi/L were considered to have Grade 3 thrombocytopenia and par. with a platelet count <25Gi/L were considered to have Grade 4 thrombocytopenia. Blood samples were collected to estimate thrombocytes at the following time points: For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate thrombocytes at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Par. experiencing thrombocytopenia (Platelets <150Gi/L) at least once within a cycle are presented in the category title as n=X,X,X,X.

  6. Maximum Duration of Thrombocytopenia Across Cycles 2 to 6 in Phase I, Estimated Using Central Laboratory Platelet Counts [Cycle 2 to Cycle 6]

    Duration of thrombocytopenia is defined as a period of time in days from the first report of a platelet count with NCI CTCAE Grade 1-4 until the first subsequent report of a platelet count no longer meeting those criteria, regardless of rescue medication usage. It was assessed between Day 1 of Cycle 2 and up to and including any Conclusion/Early Withdrawal visit assigned to the same cycle for participants completing up to 6 cycles, and between Day 1 of Cycle 2 and up to and including the end of Cycle 6 for participants continuing beyond 6 cycles. The chemotherapy cycle for Group A was 21 days and for Group B was 28 days. Blood samples were collected to estimate thrombocytes at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 2 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 2 to 6.

  7. Central Laboratory Platelet Count for Time Taken to Reach Platelet Nadir for Each Chemotherapy Cycle in Phase I [Cycle 1 to Cycle 6]

    Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. The time taken to reach platelet nadir is defined within each cycle. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet nadir count at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).

  8. Time to Recovery From Platelet Nadir for Each Chemotherapy Cycle in Phase I, Estimated Using Central Laboratory Platelet Counts [Cycle 1 to Cycle 6]

    Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. Time to recovery (TR) (>100Gi/L or >150Gi/L) from platelet nadir is defined within each cycle as the time in days from the platelet nadir to the time at which platelet count returns to >=100Gi/L or >=150Gi/L within the same cycle or up to and including Day 1 of the next cycle. For the last cycle in the study, time to recovery was calculated in the same manner but up to and including any Conclusion/Early Withdrawal visit which has been assigned to the same cycle. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet count at: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. Group B; Days 1, 4, 8, 15, 22, and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).

  9. Dose Intensity of Gemcitabine Plus Cisplatin (G+Cis)/Gemcitabine Plus Carboplatin (G+Cb) and Gemcitabine Across Chemotherapy Cycles 1 to 6 in Phase I [Cycle 1 to Cycle 6]

    Dose intensity of chemotherapy is defined as the actual dose of chemotherapy given as a percentage of the scheduled C1D1/C1D8 dose, as applicable, within this study: Cycle Dose Intensity (%) = Total Actual dose (mg/m^2) within Cycle *100/ Total Scheduled dose (mg/m^2) in Cycle 1; wherein Actual Dose (mg/m^2) = Actual dose (mg)/Body Surface Area reported on electronic case report form (eCRF).

  10. Number of Participants With at Least One Delay in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase I [All time on chemotherapy treatment]

    Any delay in a scheduled dose of gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin was evaluated for eltrombopag and placebo treated participants.

  11. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase II [From first dose of investigational product (IP) until 30 days after discontinuation of IP (Longer for AEs related to study participation)]

    AE is any untoward medical occurrence temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a MP. For marketed MPs, this also includes failure to produce expected benefits, abuse, or misuse. SAE event is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect.

  12. Number of Participants With Any Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale, Across Cycles 1-6 in Phase II [Screening, Day -5, Day 1 and 8 of Cycles 1 to 6 of 21-day cycle schedule, Day 1, 8 and 15 of cycles 1 to 6 of 28-day schedule, treatment withdrawal and 30-day follow-up]

    The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross bleeding; Grade 4=debilitating blood loss. The WHO grades were further classified into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. Baseline is defined as the Day 1 assessment or the latest possible screening assessment. Across Cycles 1-6 included all assessments after first dose of chemotherapy up to the end of Cycle 6. Data exclused for participants taking drugs that affect platelet function or anticoagulants, from the time that the medication was started.

  13. Number of Participants Requiring a Platelet Transfusion in Phase II [Screening, Day -5, throughout cycles 1 to 6 and up to 30 days after IP discontinuation]

    Platelet transfusion was used as a rescue medication for the treatment of thrombocytopenia. Number of participants requiring a platelet transfusion during Cycles 1-6 was summarized and compared between treatment groups using a logistic regression model adjusted for cycle duration. Each cycle included assessments starting at Day 1 of the cycle.

  14. Number of Participants With at Least One Delay in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase II [Cycle 1 to Cycle 6]

    Any delay in scheduled dose of gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin was evaluated for eltrombopag and placebo treated participants. Number of participants with any delay in dose during 21-day cycle or 28-day cycle, in part 1 or part 2 of the study is summarized and presented. Only those participants who actually received chemotherapy are included for the cisplatin and carboplatin components and all participants are included for the gemcitabine components (represented by n=X,X in the category titles).

  15. Number of Participants With Any Dose Reduction in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase II [Cycle 1 to Cycle 6]

    Dose reductions are required following potential drug-related toxicities. Number of participants with any dose reduction during 21-day cycle or 28-day cycle, in part 1 or part 2 of the study is summarized and presented. Only participants who actually received chemotherapy were included for the cisplatin and carboplatin components. All participants were included for the gemcitabine components.

  16. Dose Intensity of Gemcitabine Plus Cisplatin(G+Cis)/Gemcitabine Plus Carboplatin (G+Cb) and Gemcitabine Across Chemotherapy Cycles 1-6 in Phase II [Cycle 1 to Cycle 6]

    Dose intensity of chemotherapy is defined as the actual dose of chemotherapy given as a percentage of the scheduled C1D1/C1D8 dose, as applicable, within this study: cycle Dose Intensity (%) = Total Actual dose (mg/m^2) within cycle *100/ Total Scheduled dose (mg/m^2) in Cycle 1; wherein Actual Dose (mg/m^2) = Actual dose (mg)/Body Surface Area reported on eCRF. The average chemotherapy dose intensity at Day 1 across Cycles 1 to 6, Day 8 across Cycles 1 to 6 and Day 15 across Cycles 1 to 6 was summarized and compared between treatment groups using an ANCOVA model adjusted for cycle duration and part of the study.

  17. Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Hematology Parameters, at Anytime Post-Baseline in Phase II [After baseline (C1D1), on-treatment and 30 day follow-up]

    Hematology parameters with a related NCI CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment, the maximum toxicity grade reached by a participant post-Baseline was summarized. Hematology parameters included Hemoglobin (Hb) increased, Anemia, Lymphocyte count (Lym), platelet count, White Blood Cell count (WBC) and Total Absolute Neutrophil Count (Total ANC). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. participants with missing Baseline value were assumed to have normal Baseline value. Only those Participant available at the indicated time points were analyzed (represented by n=X,X in the category titles).

  18. Number of Participants With Indicated Worst-case Change From Baseline in Clinical Chemistry Laboratory Parameters Using CTCAE Toxicity Grading, at Anytime Post-Baseline in Phase II [After baseline (C1D1), on-treatment (collected on days 1 and 8 for subjects on 21-day cycle and on days 1, 8 and 15 for subjects on 28-day cycle) and 30 day follow-up]

    Clinical chemistry laboratory parameters with a related CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment. Worst-case grade change of the laboratory parameters at anytime post-Baseline is presented as "Any grade increase", "Increase to Grade 3 or Grade 4". Clinical chemistry laboratory parameters included Albumin (Al), creatinine, AST, ALT, ALP, TB, Calcium hypercalcemia (CaHy)/hypocalcemia (CaHo), Glucose hyperglycemia (GluHy)/hypoglycemia (GluHo), Potassium hypernatremia (KHy)/hyponatremia (KHo) and Sodium hypernatremia (NaHy)/hyponatremia (NaHo). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. Only those Participant available at the indicated time points were analyzed (represented by n=X,X in the category titles).

  19. Number of Participants With Change From Baseline in Creatinine of >=26.5 UMOL/L in Phase II [After baseline (C1D1), on-treatment (collected on days 1 and 8 for subjects on 21-day cycle and on days 1, 8 and 15 for subjects on 28-day cycle) and 30 day follow-up]

    Number of participants with at least 1 assessment of change from Baseline in creatinine, with increase >=26.5 UMOL/L are presented. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of IP.

  20. Number of the Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Scores at the Indicated Time Points in Phase II [Screening, C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1 and C17D1]

    ECOG-Zubrod scores for the Performance Status were defined as follows: 0: Fully active, 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2: Ambulatory and capable of all self-care but unable to carry out any work activities, 3: Capable of only limited self-care, 4: Completely disabled, 5 and Unknown: Dead. The data is presented for the participants with the ECOG performance score at different time points during the study. Only those participants available at the indicated time points were analyzed (represented by n=X,X in the category titles).

  21. Number of Participants With Electrocardiogram (ECG) Findings at Cycle 1 Day 4 (2 to 6 Hours Post-dose) in Phase II [C1D4]

    A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at screening and 2 to 6 hours post-dose on C1D4. Change in ECG findings were categorized as 'Clinically significant change (CSC): favorable', 'No change or insignificant change' or 'Clinically significant change (CSC): unfavorable' as determined by the investigator. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of investigational product. Only those participants available at the indicated time points were analyzed (represented by n=X,X in the category titles).

  22. Mean Day 8 Scheduled Pre-chemotherapy Platelet Counts Evaluated Across Cycles 1 to 6 in Phase II [Day 8 (averaged across cycles 1 to 6)]

    Scheduled pre-chemotherapy platelet count is defined within each cycle as the platelet count assessment on which the decision to give or delay chemotherapy was made. This was averaged for each subject across cycles 1 to 6 and a natural log transformation was applied to the average. The log-transformed values were compared between eltrombopag and placebo groups using an analysis of covariance (ANCOVA) model adjusting for cycle duration (21-day vs. 28-day), baseline loge(platelet count) and part of study (part 1 or 2 of phase II). The number of participants analyzed is the number with a Day 8 scheduled platelet count.

  23. Mean Day 15 Scheduled Pre-chemotherapy Platelet Counts Evaluated Across Cycles 1 to 6 in Phase II [Day 15 (averaged across cycles 1 to 6)]

    Scheduled pre-chemotherapy platelet count is defined within each cycle as the platelet count assessment on which the decision to give or delay chemotherapy was made. This was averaged for each subject across cycles 1 to 6 and a natural log transformation was applied to the average. The log-transformed values were compared between eltrombopag and placebo groups using an analysis of covariance (ANCOVA) model adjusting for cycle duration (21-day vs. 28-day), baseline loge(platelet count) and part of study (part 1 or 2 of phase II). The number of participants analyzed is the number with a Day 15 scheduled platelet count.

  24. Mean Within-subject Platelet Count Prior to Scheduled Chemotherapy Across Cycles 1 to 6 in Phase II [Day 1, Day 8, Day 15 (all averaged across cycles 1 to 6)]

    Within-subject platelet count for each par. was calculated by summing up the visit platelet counts from each of Cycles 1 to 6 and dividing it by the number of cycles in which the par. had data. The average within a treatment group was calculated by summing up the values from each par. within the treatment 21-day cycle dividing it by the number of par. These platelet counts are different from the pre-chemotherapy platelet counts for cycles where the chemotherapy dose was delayed. Average within-subject central laboratory platelet count prior to scheduled chemotherapy across Cycles 1 to 6 are summarized. Blood samples were collected on Day 1 and 8 of Cycles 1 to 6 for 21-day cycle and on Day 1, 8 and 15 from Cycles 1 to 6 for 28-day cycle to estimate the average within subject platelet count prior to scheduled chemotherapy. Only those participants available at the indicated time points were analyzed (represented by n=X,X in the category titles).

  25. Platelet Count Nadir for Each Chemotherapy Cycle in Phase II [Cycle 1 to Cycle 6]

    Platelet nadir is defined as the lowest platelet count reported after the first dose of chemotherapy within each cycle. Platelet count nadir is defined for each cycle. Blood samples were collected to estimate platelet nadir count at the following time points: 21-day cycle; Day 1, Day 4, Day 8, Day 15 and Day 17 of Cycles 1 to 6. 28-day cycle; Day 1, Day 4, Day 8, Day 15, Day 22, Day 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X).

  26. Average Daily Area Under the Platelet-time Course Across Cycles 1 to 6 in Phase II [All assessments from Cycle 1 Day 1 to last assessment in Cycle 6]

    The average daily area under the platelet-time course was normalized by dividing the area under curve by total duration. This gives an estimated average platelet value over the time period from cycles 1 to 6. Blood samples were collected to estimate platelet count at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6.

  27. Number of Participants With Thrombocytopenia of Grade 1, 2, 3 or 4 Across Cycles 1 to 6 in Phase II [Cycle 1 to Cycle 6]

    As per the CTCAE version 4.0, participants with a platelet count <LLN but >=75 x 10^9/L (Gi/L) were considered to have Grade 1 thrombocytopenia; participants with a platelet count <75Gi/L, but >=50Gi/L were considered to have Grade 2 thrombocytopenia; participants with a platelet count <50Gi/L, but >=25Gi/L were considered to have Grade 3 thrombocytopenia and participants with a platelet count <25Gi/L were considered to have Grade 4 thrombocytopenia. Blood samples were collected to estimate thrombocytes at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Participants experiencing thrombocytopenia(Platelets <150Gi/L) at least once within cycle are presented in the category title as n=X,X.

  28. Maximum Duration of Thrombocytopenia Across Cycles 1 to 6 in Phase II [Cycle 1 to Cycle 6]

    Duration of thrombocytopenia is defined as a period of time in days from the first report of a platelet count with NCI CTCAE Grade 1-4 until the first subsequent report of a platelet count no longer meeting those criteria, regardless of rescue medication usage. It was assessed between Day 1 of Cycle 2 and up to and including any Conclusion/Early Withdrawal visit assigned to the same cycle for participants completing up to 6 cycles, and between Day 1 of Cycle 2 and up to and including the end of Cycle 6 for participants continuing beyond 6 cycles. The chemotherapy cycle for 21-day cycle was 21 days and for 28-day cycle was 28 days. Blood samples were collected to estimate thrombocytes at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 2 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 2 to 6.

  29. Time Taken to Reach Platelet Nadir for Each Chemotherapy Cycle in Phase II [Cycle 1 to Cycle 6]

    Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. The time taken to reach platelet nadir is defined within each cycle. Blood samples were collected to estimate platelet nadir count at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X).

  30. Time to Recovery From Platelet Nadir for Each Chemotherapy Cycle in Phase II [Cycle 1 to Cycle 6]

    Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. TR (>100Gi/L or >150Gi/L) from platelet nadir is defined within each cycle as the time in days from the platelet nadir to the time at which platelet count returns to >=100Gi/L or >=150Gi/L within the same cycle or up to and including Day 1 of the next cycle. For the last cycle in the study, time to recovery was calculated in the same manner but up to and including any Conclusion/Early Withdrawal visit which has been assigned to the same cycle. Blood samples were collected to estimate platelet count at: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22, and 24of Cycles 1 to 6. Time to recover censored if platelet count did not return to >=100/150 Gi/L. Censored results are excluded from calculation of summary statistics. Only those participants available at indicated time points were analyzed (represented by n=X, X).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria:Inclusion Criteria Subjects eligible for enrolment in Phase I and II of the study must meet all of the following criteria:

  • Signed written informed consent.

  • Age ≥ 18 years.

  • Subjects with confirmed solid tumor and scheduled to receive at least two cycles of either gemcitabine monotherapy OR gemcitabine in combination with carboplatin or cisplatin at the same dosages and schedule in the study. Novel anticancer agents (e.g. bevacizumab, erlotinib) may be allowed if considered a standard treatment by the investigator. Subjects with only ONE current diagnosis of primary solid tumor will be allowed into the study.

  • Note: For patients scheduled to receive any novel anticancer agents (e.g. bevacizumab, erlotinib), consultation and approval from the GSK medical monitor should occur before the subject is enrolled into the study.

  • Life expectancy of at least 3 months, in the opinion of the investigator.

  • ECOG-Zubrod performance status ≤ 2

  • For Phase I: Pre-chemotherapy platelet count ≤ 300 Gi/L in the screening period before the subject start their first planned cycle of treatment with gemcitabine monotherapy OR gemcitabine in combination with carboplatin or cisplatin in the study.

  • For Phase II (Part 1 and 2): Subjects must meet one of the following platelet count entry criteria:

  1. Subjects have not started the first cycle in this disease setting and have a platelet count < 150 Gi/L in the screening period as measured within 3 days before Day -5, OR

  2. Subjects started chemotherapy for this disease setting and had platelet count < 150 Gi/L on Day 1 in the preceding cycle before entry into the study, OR

  3. Platelet count < 100 Gi/L at Day 8 in the preceding cycle before entry into the study, OR

  4. Platelet count < 100 Gi/L at Day 15 in the preceding cycle before entry into the study (for subjects receiving Gemcitabine monotherapy) Note: For any of these platelet counts, a repeated platelet count may be allowed only once to ensure that the subject meets the above platelet count criteria and the latest count will be taken for the assessment of eligibility to the study..

  • Subjects with previous chemotherapy treatment in a previous disease setting are allowed provided they have recovered from chemotherapy related toxicity except alopecia (and the lab parameters mentioned in Inclusion criteria in #9).

  • Adequate organ function during screening period defined by the criteria below (adequate baseline organ function):

  • SYSTEM LABORATORY VALUES

  • Hematologic

  • Platelets, see Inclusion criteria

  • ANC (absolute neutrophil count) ≥1.5 × 109/L

  • Hemoglobin ≥9 g/dL

  • Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) Within 80 to 120% of the normal range

  • Hepatic

  • Albumin ≥2.5 g/dL

  • Serum bilirubin ≤1.5 x ULN AST and ALT

  • 3 × ULN without liver metastases

  • 5 × ULN if documented liver metastases

  • Renal

  • Serum Creatinine ≤ 1.2 x ULN

  • Subjects with AST, ALT or bilirubin values outside the range(s) in the table due to Gilbert's syndrome or asymptomatic gall stones are not excluded.

  • Women of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to randomization and agree to use effective contraception, during the study and for 4 weeks following the last dose of investigational product.

  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from 2 weeks prior to randomization until 13 weeks after the last dose of study treatment.

  • Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

Exclusion Criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:

  • Lactating females.

  • 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), unstable angina, or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block) at study entry, or myocardial infarction within the preceding 6 months. Subjects with a34 pacemaker or defibrillator are not excluded provided that their cardiac function is within normal ranges.

  • Note: For patients with pre-existing NYHA Grade II cardiovascular disease, the investigator should consult with GSK medical monitor before enrolling the subject into the study.

  • Patients with known factor V leiden, antiphospholipid antibody syndrome, prothrombin gene mutations, ATIII deficiency, protein C deficiency, protein S deficiency OR recent history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the preceding 6 months.

  • Note: for patients with known risk factors for thromboembolism e.g., diabetes, hypercholesterolemia, recent major surgery etc., the investigator should consult with GSK medical monitor before enrolling the patient into the study and all risk factors should be documented in the CRF.

  • Prior surgery within two weeks before study randomization or radiotherapy (RT) within four weeks before study randomization. Subjects with prior surgery or RT are not permitted into the study unless they have completely recovered from surgery and/or acute RT toxicity except for alopecia.

  • Note: Note: patients with minor surgeries or outpatient procedures (e.g. insertion of central venous catheter) are immediately allowed in the study provided that there were no complications from the procedure or surgery.

  • History of prior radiotherapy to more than 20% bone marrow bearing sites.

  • History of platelet agglutination abnormality, platelet disorders or dysfunction or bleeding disorder that prevents reliable measurement of platelet counts.

  • 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 unless properly treated. Subjects with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to randomization will be excluded.

  • Treated brain metastases are defined

  • Having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed.

  • Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician.

Note: if subject has performed a CT scan immediately prior to the screening period and CT could not be repeated, an MRI should be performed in the screening period to exclude the development of brain metastases and/or the progression of the pre-existing brain metastatic lesion(s).

  • Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of investigational product in the study. Concurrent participation in another interventional clinical trial or administration of any investigational drug during the study is also not permitted.

  • A known immediate or delayed hypersensitivity reaction or idiosyncrasy that, in the opinion of the Investigator or GSK Medical Monitor is due to drugs chemically related to eltrombopag or excipients (e.g. mannitol).

  • Subjects with known Hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV). Subjects with Gilbert's Syndrome are permitted into the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Sedona Arizona United States 86336
2 GSK Investigational Site Hot Springs Arkansas United States 71913
3 GSK Investigational Site Rancho Cucamonga California United States 91730
4 GSK Investigational Site Norwich Connecticut United States 06360
5 GSK Investigational Site Jacksonville Florida United States 32256
6 GSK Investigational Site New Port Richey Florida United States 34655
7 GSK Investigational Site Rome Georgia United States 30165
8 GSK Investigational Site Savannah Georgia United States 31405
9 GSK Investigational Site Wichita Kansas United States 67214
10 GSK Investigational Site Bethesda Maryland United States 20817
11 GSK Investigational Site Rockville Maryland United States 20850
12 GSK Investigational Site Columbia Missouri United States 65201
13 GSK Investigational Site Las Vegas Nevada United States 89169
14 GSK Investigational Site Cherry Hill New Jersey United States 08003
15 GSK Investigational Site Albany New York United States 12206
16 GSK Investigational Site Greensboro North Carolina United States 27403
17 GSK Investigational Site Bend Oregon United States 97701
18 GSK Investigational Site Philadelphia Pennsylvania United States 19106
19 GSK Investigational Site Wynnewood Pennsylvania United States 19096
20 GSK Investigational Site Providence Rhode Island United States 02903
21 GSK Investigational Site Providence Rhode Island United States 02906
22 GSK Investigational Site Greenville South Carolina United States 29605
23 GSK Investigational Site Arlington Texas United States 76014
24 GSK Investigational Site Austin Texas United States 78731
25 GSK Investigational Site Bedford Texas United States 76022
26 GSK Investigational Site Dallas Texas United States 75246
27 GSK Investigational Site San Antonio Texas United States 78217
28 GSK Investigational Site Tyler Texas United States 75702
29 GSK Investigational Site Norfolk Virginia United States 23502
30 GSK Investigational Site Edmunds Washington United States 98026
31 GSK Investigational Site Tacoma Washington United States 98405
32 GSK Investigational Site Vancouver Washington United States 98684
33 GSK Investigational Site Yakima Washington United States 98902
34 GSK Investigational Site Charleroi Belgium 6000
35 GSK Investigational Site Leuven Belgium 3000
36 GSK Investigational Site Libramont Belgium 6800
37 GSK Investigational Site Namur Belgium 5000
38 GSK Investigational Site Edmonton Alberta Canada T6G 1Z2
39 GSK Investigational Site Toronto Ontario Canada M5G 2M9
40 GSK Investigational Site Olomouc Czech Republic 775 20
41 GSK Investigational Site Praha 10 Czech Republic 100 00
42 GSK Investigational Site Praha 5 Czech Republic 150 06
43 GSK Investigational Site Helsinki Finland 00290
44 GSK Investigational Site Tampere Finland 33520
45 GSK Investigational Site Freiburg Baden-Wuerttemberg Germany 79106
46 GSK Investigational Site Augsburg Bayern Germany 86150
47 GSK Investigational Site Muenchen Bayern Germany 80335
48 GSK Investigational Site Muenchen Bayern Germany 81241
49 GSK Investigational Site Goslar Niedersachsen Germany 38642
50 GSK Investigational Site Hannover Niedersachsen Germany 30171
51 GSK Investigational Site Essen Nordrhein-Westfalen Germany 45122
52 GSK Investigational Site Dresden Sachsen Germany 01127
53 GSK Investigational Site Dresden Sachsen Germany 01307
54 GSK Investigational Site Berlin Germany 10367
55 GSK Investigational Site Berlin Germany 14169
56 GSK Investigational Site Athens Greece 115 27
57 GSK Investigational Site Athens Greece 115 28
58 GSK Investigational Site Heraklion, Crete Greece 71100
59 GSK Investigational Site Thessaloniki Greece 564 29
60 GSK Investigational Site Budapest Hungary 1529
61 GSK Investigational Site Győr Hungary 9022
62 GSK Investigational Site Kaposvár Hungary 7400
63 GSK Investigational Site Törökbálint Hungary
64 GSK Investigational Site Zalaegerszeg Hungary 8900
65 GSK Investigational Site Madurai India 625107
66 GSK Investigational Site Pune India 411001
67 GSK Investigational Site Pune India 411004
68 GSK Investigational Site Dublin Ireland 4
69 GSK Investigational Site Dublin Ireland 7
70 GSK Investigational Site Tallaght, Dublin Ireland 24
71 GSK Investigational Site Ashkelon Israel 78306
72 GSK Investigational Site Haifa Israel 34362
73 GSK Investigational Site Jerusalem Israel 91031
74 GSK Investigational Site Kfar Saba Israel 44281
75 GSK Investigational Site Tel Aviv Israel 64239
76 GSK Investigational Site Zrifin Israel 70300
77 GSK Investigational Site Modena Emilia-Romagna Italy 41100
78 GSK Investigational Site Aviano (PN) Friuli-Venezia-Giulia Italy 33081
79 GSK Investigational Site Milano Lombardia Italy 20133
80 GSK Investigational Site Sassari Sardegna Italy 07100
81 GSK Investigational Site Pisa Toscana Italy 56126
82 GSK Investigational Site Bialystok Poland 15-540
83 GSK Investigational Site Konin Poland 62-500
84 GSK Investigational Site Olsztyn Poland 10-357
85 GSK Investigational Site Poznan Poland 60-569
86 GSK Investigational Site Poznan Poland 61-866

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01147809
Other Study ID Numbers:
  • 112765
First Posted:
Jun 22, 2010
Last Update Posted:
Apr 18, 2016
Last Verified:
Mar 1, 2016
Keywords provided by GlaxoSmithKline
Solid Tumor
Eltrombopag
chemotherapy-induced thrombocytopenia
Thrombocytopenia
Additional relevant MeSH terms:
Thrombocytopenia

Study Results

Participant Flow

Recruitment Details Participants (par.) with solid tumors receiving gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin were eligible for enrollment into the study. The study comprised of 2 phases (I & II), with eligible par. being randomized to receive placebo or eltrombopag in each phase.
Pre-assignment Detail A total of 108 par. were randomized, of which 101 par. received at least 1 dose of study drug. A maximum of 6 cycles (with some exceptions) of chemotherapy with eltrombopag/placebo were allowed in each phase (either 21-day or 28-day cycle) followed by the 30 day Follow-up visit.
Arm/Group Title Phase I: 21-Day Cycle Placebo Phase I: 21-Day Cycle Eltrombopag 100 mg Phase I: 28-Day Cycle Placebo Phase I: 28-Day Cycle Eltrombopag 100 mg Phase II: Placebo Phase II: Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of the 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of the 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of the 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of the 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Period Title: Phase I (168 Days)
STARTED 3 9 4 10 0 0
COMPLETED 2 8 2 5 0 0
NOT COMPLETED 1 1 2 5 0 0
Period Title: Phase I (168 Days)
STARTED 0 0 0 0 23 52
Ongoing 0 0 0 0 1 0
COMPLETED 0 0 0 0 7 19
NOT COMPLETED 0 0 0 0 16 33

Baseline Characteristics

Arm/Group Title Phase I: 21-Day Cycle Placebo Phase I: 21-Day Cycle Eltrombopag 100 mg Phase I: 28-Day Cycle Placebo Phase I: 28-Day Cycle Eltrombopag 100 mg Phase II: Placebo Phase II: Eltrombopag 100 mg Total
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Total of all reporting groups
Overall Participants 3 9 4 10 23 52 101
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
53.3
(3.79)
53.8
(11.27)
61.8
(22.82)
65.6
(8.41)
64.4
(9.96)
66.3
(8.98)
64.1
(10.56)
Sex: Female, Male (Count of Participants)
Female
1
33.3%
7
77.8%
3
75%
3
30%
13
56.5%
23
44.2%
50
49.5%
Male
2
66.7%
2
22.2%
1
25%
7
70%
10
43.5%
29
55.8%
51
50.5%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage
1
33.3%
1
11.1%
0
0%
0
0%
1
4.3%
0
0%
3
3%
White
2
66.7%
8
88.9%
3
75%
8
80%
22
95.7%
52
100%
95
94.1%
Central/South Asian Heritage
0
0%
0
0%
1
25%
0
0%
0
0%
0
0%
1
1%
Japanese/East Asian Heritage/South East Asian
0
0%
0
0%
0
0%
2
20%
0
0%
0
0%
2
2%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase I
Description AEs are coded using the standard Medical Dictionary for Regulatory Activities (MedDRA) and were graded by the investigator according to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), version 4.0. AE is any untoward medical occurrence temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a MP. For marketed MPs, this also includes failure to produce expected benefits, abuse, or misuse. SAE event is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect.
Time Frame From Cycle 1, Day 1 (C1D1) until at least 30 days post-investigational product discontinuation (longer for AEs considered related to study participation)

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Any AE Pre-therapy
3
100%
8
88.9%
4
100%
9
90%
Any SAE Pre-therapy
1
33.3%
0
0%
0
0%
1
10%
Any AE On-therapy+30 days
3
100%
9
100%
3
75%
10
100%
Any SAE On-therapy+30 days
1
33.3%
5
55.6%
1
25%
2
20%
Any AE Post-therapy
0
0%
0
0%
0
0%
3
30%
Any SAE Post-therapy
0
0%
0
0%
0
0%
1
10%
Treatment-related AEs On-therapy+30 days
2
66.7%
3
33.3%
1
25%
6
60%
>=Grade 3 AEs On-therapy+30 days
2
66.7%
7
77.8%
2
50%
3
30%
Liver AEs On-therapy+30 days
0
0%
2
22.2%
0
0%
2
20%
Renal AEs On-therapy+30 days
0
0%
3
33.3%
2
50%
0
0%
Thromboembolic events On-therapy+30 days
0
0%
2
22.2%
0
0%
1
10%
Cardiac AEs On-therapy+30 days
0
0%
1
11.1%
1
25%
1
10%
Neutropenia On-therapy+30 days
3
100%
4
44.4%
2
50%
5
50%
Anemia On-therapy+30 days
1
33.3%
4
44.4%
1
25%
4
40%
Thrombocytopenia On-therapy+30 days
2
66.7%
3
33.3%
3
75%
3
30%
Leukopenia On-therapy+30 days
1
33.3%
2
22.2%
2
50%
3
30%
Thrombocytosis On-therapy+30 days
2
66.7%
2
22.2%
1
25%
2
20%
Platelet count increased On-therapy+30 days
0
0%
0
0%
0
0%
3
30%
2. Primary Outcome
Title Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Hematology Parameters, at Anytime Post-Baseline in Phase I
Description Hematology parameters with a related NCI CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment, the maximum toxicity grade reached by a participant post-Baseline was summarized. Hematology parameters included hemoglobin (increased), hemoglobin (anemia), lymphocytes (increased), lymphocytes (decreased), total absolute neutrophil count (ANC), platelets (PLT) and white blood cells (WBC). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. Only those participant available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).
Time Frame After Baseline (C1D1), on-treatment and 30 day follow-up

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Hemoglobin (Increased), Grade 0, n=3,9,4,10
3
100%
9
100%
4
100%
10
100%
Hemoglobin (Anemia), Grade 1, n=3,9,4,10
2
66.7%
1
11.1%
0
0%
3
30%
Hemoglobin (Anemia), Grade 2, n=3,9,4,10
0
0%
6
66.7%
2
50%
4
40%
Hemoglobin (Anemia), Grade 3, n=3,9,4,10
1
33.3%
2
22.2%
2
50%
3
30%
Lymphocytes (Increased), Grade 0, n=3,9,4,10
3
100%
8
88.9%
4
100%
10
100%
Lymphocytes (Increased), Grade 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
0
0%
Lymphocytes (Decreased), Grade 0, n=3,9,4,10
1
33.3%
1
11.1%
0
0%
3
30%
Lymphocytes (Decreased), Grade 1, n=3,9,4,10
0
0%
2
22.2%
0
0%
0
0%
Lymphocytes (Decreased), Grade 2, n=3,9,4,10
1
33.3%
1
11.1%
1
25%
4
40%
Lymphocytes (Decreased), Grade 3, n=3,9,4,10
1
33.3%
5
55.6%
3
75%
2
20%
Lymphocytes (Decreased), Grade 4, n=3,9,4,10
0
0%
0
0%
0
0%
1
10%
Total ANC, Grade 0, n=1,2,1,2
0
0%
2
22.2%
1
25%
0
0%
Total ANC, Grade 1, n=1,2,1,2
1
33.3%
0
0%
0
0%
2
20%
PLT, Grade 0, n=3,9,4,10
0
0%
1
11.1%
0
0%
2
20%
PLT, Grade 1, n=3,9,4,10
0
0%
1
11.1%
1
25%
3
30%
PLT, Grade 2, n=3,9,4,10
0
0%
3
33.3%
1
25%
3
30%
PLT, Grade 3, n=3,9,4,10
1
33.3%
2
22.2%
2
50%
1
10%
PLT, Grade 4, n=3,9,4,10
2
66.7%
2
22.2%
0
0%
1
10%
WBC, Grade 0, n=3,9,4,10
0
0%
0
0%
1
25%
2
20%
WBC, Grade 1, n=3,9,4,10
0
0%
1
11.1%
0
0%
2
20%
WBC, Grade 2, n=3,9,4,10
2
66.7%
2
22.2%
1
25%
2
20%
WBC, Grade 3, n=3,9,4,10
1
33.3%
5
55.6%
2
50%
3
30%
WBC, Grade 4, n=3,9,4,10
0
0%
1
11.1%
0
0%
1
10%
3. Primary Outcome
Title Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Clinical Chemistry Laboratory Parameters, at Anytime Post-Baseline in Phase I
Description Clinical chemistry laboratory parameters with a related NCI CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment. Clinical chemistry laboratory parameters included albumin (Alb), urea/blood urea nitrogen (BUN), creatinine, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), direct bilirubin (DB) and international normalized ratio/Prothrombin time (PT). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. Only those participants available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).
Time Frame After Baseline (C1D1), on-treatment and 30 day follow-up

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Alb, Grade 0, n=3,9,4,10
2
66.7%
4
44.4%
0
0%
4
40%
Alb, Grade 1, n=3,9,4,10
1
33.3%
2
22.2%
2
50%
5
50%
Alb, Grade 2, n=3,9,4,10
0
0%
3
33.3%
1
25%
1
10%
Alb, Grade 3, n=3,9,4,10
0
0%
0
0%
1
25%
0
0%
ALP, Grade 0, n=3,9,4,10
2
66.7%
3
33.3%
3
75%
6
60%
ALP, Grade 1, n=3,9,4,10
1
33.3%
5
55.6%
1
25%
1
10%
ALP, Grade 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
2
20%
ALP, Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
1
10%
ALT, Grade 0, n=3,9,4,10
2
66.7%
3
33.3%
3
75%
4
40%
ALT, Grade 1, n=3,9,4,10
1
33.3%
4
44.4%
1
25%
5
50%
ALT, Grade 2, n=3,9,4,10
0
0%
2
22.2%
0
0%
0
0%
ALT, Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
1
10%
AST, Grade 0, n=3,9,4,10
2
66.7%
4
44.4%
2
50%
5
50%
AST, Grade 1, n=3,9,4,10
1
33.3%
3
33.3%
2
50%
3
30%
AST, Grade 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
1
10%
AST, Grade 3, n=3,9,4,10
0
0%
1
11.1%
0
0%
1
10%
TB, Grade 0, n=3,9,4,10
3
100%
5
55.6%
3
75%
8
80%
TB, Grade 1, n=3,9,4,10
0
0%
2
22.2%
0
0%
0
0%
TB, Grade 2, n=3,9,4,10
0
0%
2
22.2%
1
25%
0
0%
TB, Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
2
20%
Ca (hypercalcemia), Grade 0, n=3,9,4,10
3
100%
8
88.9%
4
100%
10
100%
Ca (hypercalcemia), Grade 1, n=3,9,4,10
0
0%
1
11.1%
0
0%
0
0%
Ca (hypercalcemia), Grade 2, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Ca (hypercalcemia), Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Ca (hypocalcemia), Grade 0, n=3,9,4,10
2
66.7%
7
77.8%
3
75%
9
90%
Ca (hypocalcemia), Grade 1, n=3,9,4,10
1
33.3%
1
11.1%
0
0%
0
0%
Ca (hypocalcemia), Grade 2, n=3,9,4,10
0
0%
1
11.1%
1
25%
1
10%
Ca (hypocalcemia), Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Creatinine, Grade 0, n=3,9,4,10
3
100%
7
77.8%
4
100%
9
90%
Creatinine, Grade 1, n=3,9,4,10
0
0%
1
11.1%
0
0%
1
10%
Creatinine, Grade 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
0
0%
Creatinine, Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Glu (hyperglycemia), Grade 0, n=3,9,4,10
2
66.7%
3
33.3%
1
25%
2
20%
Glu (hyperglycemia), Grade 1, n=3,9,4,10
0
0%
4
44.4%
2
50%
4
40%
Glu (hyperglycemia), Grade 2, n=3,9,4,10
1
33.3%
2
22.2%
1
25%
4
40%
Glu (hyperglycemia), Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Glu (hypoglycemia), Grade 0, n=3,9,4,10
3
100%
8
88.9%
4
100%
8
80%
Glu (hypoglycemia), Grade 1, n=3,9,4,10
0
0%
0
0%
0
0%
1
10%
Glu (hypoglycemia), Grade 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
1
10%
Glu (hypoglycemia), Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
K (hyperkalemia), Grade 0, n=3,9,4,10
1
33.3%
8
88.9%
3
75%
9
90%
K (hyperkalemia), Grade 1, n=3,9,4,10
2
66.7%
1
11.1%
0
0%
0
0%
K (hyperkalemia), Grade 2, n=3,9,4,10
0
0%
0
0%
1
25%
1
10%
K (hyperkalemia), Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
K (hypokalemia), Grade 0, n=3,9,4,10
2
66.7%
5
55.6%
3
75%
7
70%
K (hypokalemia), Grade 1, n=3,9,4,10
1
33.3%
3
33.3%
1
25%
3
30%
K (hypokalemia), Grade 2, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
K (hypokalemia), Grade 3, n=3,9,4,10
0
0%
1
11.1%
0
0%
0
0%
Na (hypernatremia), Grade 0, n=3,9,4,10
2
66.7%
9
100%
3
75%
10
100%
Na (hypernatremia), Grade 1, n=3,9,4,10
1
33.3%
0
0%
1
25%
0
0%
Na (hypernatremia), Grade 2, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Na (hypernatremia), Grade 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Na (hyponatremia), Grade 0, n=3,9,4,10
2
66.7%
4
44.4%
2
50%
5
50%
Na (hyponatremia), Grade 1, n=3,9,4,10
1
33.3%
4
44.4%
0
0%
5
50%
Na (hyponatremia), Grade 2, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
Na (hyponatremia), Grade 3, n=3,9,4,10
0
0%
1
11.1%
2
50%
0
0%
4. Primary Outcome
Title Number of Participants With a Change From Baseline in Creatinine of >=26.5 Micromoles/Liter (UMOL/L) in Phase I
Description The number of participants with at least 1 change from Baseline in creatinine, with an increase >=26.5 UMOL/L are reported. Creatinine clearance is estimated using the Cockcroft-Gault formula which is a method to approximate kidney function. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1.
Time Frame After Baseline (C1D1), on-treatment and 30 day follow-up

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Number [Participants]
0
0%
3
33.3%
1
25%
2
20%
5. Primary Outcome
Title Number of the Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Scores at the Indicated Time Points in Phase I
Description ECOG-Zubrod scores for the performance status are defined as follows: Score 0: Fully active, 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2: ambulatory and capable of all self-care but unable to carry out any work activities, 3: capable of only limited self-care, 4: completely disabled, 5: dead. The data is presented for the participants with the ECOG performance score at the indicated time points during the study.
Time Frame Screening, C1D1, C2D1, C2D8, C2D15, C3D1, C4D1, C4D22, C5D1, C5D8, C6D1, C6D15

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Screening, Score 0, n=3,9,4,10
3
100%
5
55.6%
1
25%
3
30%
Screening, Score 1, n=3,9,4,10
0
0%
3
33.3%
3
75%
7
70%
Screening, Score 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
0
0%
Screening, Score 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
C1D1, Score 0, n=3,9,4,10
3
100%
5
55.6%
2
50%
3
30%
C1D1, Score 1, n=3,9,4,10
0
0%
3
33.3%
2
50%
7
70%
C1D1, Score 2, n=3,9,4,10
0
0%
1
11.1%
0
0%
0
0%
C1D1, Score 3, n=3,9,4,10
0
0%
0
0%
0
0%
0
0%
C2D1, Score 0, n=3,8,4,10
1
33.3%
3
33.3%
2
50%
2
20%
C2D1, Score 1, n=3,8,4,10
1
33.3%
4
44.4%
1
25%
8
80%
C2D1, Score 2, n=3,8,4,10
1
33.3%
1
11.1%
1
25%
0
0%
C2D1, Score 3, n=3,8,4,10
0
0%
0
0%
0
0%
0
0%
C2D8, Score 0, n=1,0,1,0
1
33.3%
NA
NaN
0
0%
NA
NaN
C2D8, Score 1, n=1,0,1,0
0
0%
NA
NaN
0
0%
NA
NaN
C2D8, Score 2, n=1,0,1,0
0
0%
NA
NaN
1
25%
NA
NaN
C2D8, Score 3, n=1,0,1,0
1
33.3%
NA
NaN
0
0%
NA
NaN
C2D15, Score 0, n=0,1,0,1
NA
NaN
0
0%
NA
NaN
0
0%
C2D15, Score 1, n=0,1,0,1
NA
NaN
0
0%
NA
NaN
1
10%
C2D15, Score 2, n=0,1,0,1
NA
NaN
1
11.1%
NA
NaN
0
0%
C2D15, Score 3, n=0,1,0,1
NA
NaN
0
0%
NA
NaN
0
0%
C3D1, Score 0, n=2,6,2,7
1
33.3%
2
22.2%
2
50%
4
40%
C3D1, Score 1, n=2,6,2,7
1
33.3%
2
22.2%
0
0%
3
30%
C3D1, Score 2, n=2,6,2,7
0
0%
1
11.1%
0
0%
0
0%
C3D1, Score 3, n=2,6,2,7
0
0%
1
11.1%
0
0%
0
0%
C4D1, Score 0, n=2,6,1,7
1
33.3%
1
11.1%
0
0%
4
40%
C4D1, Score 1, n=2,6,1,7
1
33.3%
3
33.3%
1
25%
3
30%
C4D1, Score 2, n=2,6,1,7
0
0%
1
11.1%
0
0%
0
0%
C4D1, Score 3, n=2,6,1,7
0
0%
1
11.1%
0
0%
0
0%
C4D22, Score 0, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
0
0%
C4D22, Score 1, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
0
0%
C4D22, Score 2, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
1
10%
C4D22, Score 3, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
0
0%
C5D1, Score 0, n=1,3,1,4
0
0%
0
0%
0
0%
2
20%
C5D1, Score 1, n=1,3,1,4
1
33.3%
1
11.1%
1
25%
2
20%
C5D1, Score 2, n=1,3,1,4
0
0%
1
11.1%
0
0%
0
0%
C5D1, Score 3, n=1,3,1,4
0
0%
1
11.1%
0
0%
0
0%
C5D8, Score 0, n=0,1,0,0
NA
NaN
0
0%
NA
NaN
NA
NaN
C5D8, Score 1, n=0,1,0,0
NA
NaN
0
0%
NA
NaN
NA
NaN
C5D8, Score 2, n=0,1,0,0
NA
NaN
0
0%
NA
NaN
NA
NaN
C5D8, Score 3, n=0,1,0,0
NA
NaN
1
11.1%
NA
NaN
NA
NaN
C6D1, Score 0, n=1,1,1,4
0
0%
1
11.1%
0
0%
2
20%
C6D1, Score 1, n=1,1,1,4
1
33.3%
0
0%
1
25%
2
20%
C6D1, Score 2, n=1,1,1,4
0
0%
0
0%
0
0%
0
0%
C6D1, Score 3, n=1,1,1,4
0
0%
0
0%
0
0%
0
0%
C6D15, Score 0, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
0
0%
C6D15, Score 1, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
1
10%
C6D15, Score 2, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
0
0%
C6D15, Score 3, n=0,0,0,1
NA
NaN
NA
NaN
NA
NaN
0
0%
6. Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Findings at Anytime Post-Baseline in Phase I
Description A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at screening and post-dose on C2D4. Three further ECGs were carried out at C2D8, C5D8 and C6D15. Change in ECG findings were categorized as 'Clinically significant change: favorable', 'No change or insignificant change' or 'Clinically significant change (CSC): unfavorable' as determined by the investigator. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Any time post-Baseline is defined by counting the participants under the worst result experienced post-Baseline. The best to worst order is 'Clinically significant change: favorable', 'No change or insignificant change', and then 'Clinically significant change (CSC): unfavorable. Only those participants available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).
Time Frame C2D4, C2D8, C5D8, C6D15

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
No change or insignificant change n=3,9,3,8
3
100%
8
88.9%
3
75%
7
70%
CSC: unfavorable, n=3,9,3,8
0
0%
1
11.1%
0
0%
1
10%
7. Primary Outcome
Title Mean Day 1 Scheduled Pre-chemotherapy Platelet Count Evaluated Across Cycles 1 to 6 in Phase II
Description Scheduled pre-chemotherapy platelet count is defined within each cycle as the platelet count assessment on which the decision to give or delay chemotherapy was made. This was averaged for each participant across Cycles 1 to 6 and a natural log transformation was applied to the average. The log-transformed values were compared between eltrombopag and placebo groups using an analysis of covariance (ANCOVA) model adjusting for cycle duration (21-day vs. 28-day), Baseline loge(platelet count) and part of study (part 1 or 2 of phase II). Only those participants available at indicated time points were analyzed (represented by n=X,X).
Time Frame Day 1 (averaged across cycles 1 to 6)

Outcome Measure Data

Analysis Population Description
Intent-to Treat (ITT) Population: all randomized participants.
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 48
Geometric Mean (Geometric Coefficient of Variation) [Giga (10^9) cells per liter (Gi/L)]
193.34
(54.5)
246.20
(49.8)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 21-Day Cycle Placebo, 21-Day Cycle Eltrombopag 100 mg
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.103
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Percent difference
Estimated Value 21.1
Confidence Interval (2-Sided) 95%
-3.9 to 52.5
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Average Pre-chemotherapy Platelet Count at the Indicated Time Points in Phase I
Description Pre-chemotherapy platelet count is defined for Cycle 1 as the platelet count (from central laboratory data) immediately preceding the first dose of chemotherapy within Cycle 1. For all subsequent cycles it is defined as the platelet count (from central laboratory data) immediately preceding, but limited to within 2 days prior to the first dose of chemotherapy at Day 1. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet count at the following time points: Group A; Days 1 and 8 of Cycles 1 to 6. Group B; Days 1, 8 and 15 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).
Time Frame C1D1, C1D8, C1D15, C2D1, C2D8, C2D15, C3D1, C3D8, C3D15, C4D1,C4D8, C4D15, C5D1,C5D8, C5D15, C6D1,C6D8 and C6D15

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
C1 D1, n=3,9,4,9
239.3
(75.87)
244.8
(48.47)
223.8
(79.96)
207.7
(65.51)
C1 D8, n=3,6,3,9
180.7
(65.03)
143.8
(33.88)
144.0
(44.17)
135.6
(52.52)
C1 D15, n=0,0,2, 6
NA
(NA)
NA
(NA)
135.0
(84.85)
97.5
(39.15)
C2 D1, n=2,9,4,8
443.0
(168.29)
545.8
(131.66)
284.8
(84.11)
473.3
(117.07)
C2 D8, n=2,7,3,9
221.0
(94.75)
335.6
(134.06)
163.3
(35.30)
333.0
(146.59)
C2 D15, n=0,0,2,6
NA
(NA)
NA
(NA)
80.5
(0.71)
142.7
(63.14)
C3 D1, n=2,5,2,7
464.0
(36.77)
484.6
(188.16)
290.5
(180.31)
435.4
(145.57)
C3 D8, n=2,6,2,5
285.0
(39.60)
292.2
(161.11)
293.0
(199.40)
465.2
(260.20)
C3 D15, n=0,0,2,5
NA
(NA)
NA
(NA)
92.0
(45.25)
183.4
(119.12)
C4 D1, n=1,6,1,6
298.0
(NA)
394.7
(154.28)
609.0
(NA)
388.3
(166.07)
C4 D8, n=1,5,1,6
261.0
(NA)
249.8
(122.29)
335.0
(NA)
366.5
(143.75)
C4 D15, n=0,0,1,6
NA
(NA)
NA
(NA)
86.0
(NA)
169.8
(120.56)
C5 D1, n=1,2,1,4
245.0
(NA)
529.5
(340.12)
337.0
(NA)
406.0
(174.89)
C5 D8, n=1,1,1,4
144.0
(NA)
123.0
(NA)
311.0
(NA)
403.5
(195.31)
C5 D15, n=0,0,1,4
NA
(NA)
NA
(NA)
75.0
(NA)
140.5
(42.93)
C6 D1, n=1,1,1,3
512.0
(NA)
123.0
(NA)
440.0
(NA)
360.3
(133.45)
C6 D8, n=1,1,0,3
251.0
(NA)
137.0
(NA)
NA
(NA)
428.0
(210.71)
C6 D15, n=0,0,1,2
NA
(NA)
NA
(NA)
113.0
(NA)
101.0
(48.08)
9. Secondary Outcome
Title Average Within-subject Central Laboratory Platelet Count Prior to Scheduled Chemotherapy Across Cycles 2 to 6 in Phase I
Description Within-subject platelet count for each participant was calculated by summing up the visit platelet counts from each of Cycles 1 to 6 and dividing it by the number of cycles in which the participant had data. The average within a treatment group was calculated by summing up the values from each participant within the treatment group and dividing it by the number of participants. These platelet counts are different from the pre-chemotherapy platelet counts for cycles where the chemotherapy dose was delayed. Average within-subject central laboratory platelet count prior to scheduled chemotherapy across Cycles 2 to 6 are summarized. Blood samples were collected on Days 1 and 8 of Cycles 2 to 6 for Group A and on Days 1, 8 and 15 from Cycles 2 to 6 for Group B to estimate the average within subject platelet count prior to scheduled chemotherapy. Only those participants available at the indicated time points were analyzed (represented by n=X,X,X,X in the category titles).
Time Frame Day 1 (averaged across Cycles 2 to 6), Day 8 (averaged across Cycles 2 to 6)

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
G+Cb, Day 1, n=1,3,0,0
296.80
(NA)
275.00
(144.253)
NA
(NA)
NA
(NA)
G+Cb, Day 8, n=1,3,0,0
235.00
(NA)
232.10
(77.329)
NA
(NA)
NA
(NA)
G+Cis, Day 1, n=2,6,0,0
322.50
(82.731)
526.00
(86.408)
NA
(NA)
NA
(NA)
G+Cis, Day 8, n=2,6,0,0
326.85
(119.006)
296.75
(119.342)
NA
(NA)
NA
(NA)
Gm, Day1, n=0,0,4,9
NA
(NA)
NA
(NA)
309.20
(123.133)
442.79
(114.593)
Gm, Day8, n=0,0,4,10
NA
(NA)
NA
(NA)
204.20
(80.822)
355.09
(148.539)
Gm, Day15, n=0,0,3,10
NA
(NA)
NA
(NA)
75.37
(18.292)
164.24
(94.905)
10. Secondary Outcome
Title Platelet Count Nadir for Each Chemotherapy Cycle in Phase I
Description Platelet nadir is defined as the lowest platelet count (from central laboratory data) reported after the first dose of chemotherapy within each cycle. Platelet count nadir is defined for each cycle. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet nadir count at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 and 2, at Days 1, 4, 8, 15 and 17 of Cycle 3 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Cycle 1, n=3,9,4,10
30.67
(20.404)
106.56
(113.338)
60.50
(22.664)
99.00
(75.700)
Cycle 2, n=2,9,4,10
66.00
(9.899)
122.44
(115.794)
103.50
(62.952)
135.50
(73.951)
Cycle 3, n=2,7,2,7
47.00
(4.243)
88.29
(71.807)
78.50
(43.134)
151.00
(111.946)
Cycle 4, n=2,6,1,7
76.50
(4.950)
87.50
(79.173)
86.00
(NA)
142.86
(91.908)
Cycle 5, n=1,2,1,4
14.00
(NA)
148.00
(182.434)
75.00
(NA)
113.25
(34.683)
Cycle 6, n=1,1,1,4
24.00
(NA)
13.00
(NA)
110.00
(NA)
122.75
(63.163)
11. Secondary Outcome
Title Central Laboratory Average Daily Area Under the Curve Platelet-time Course Across Cycles 2 to 6 in Phase I
Description The average daily area under the platelet-time course was normalized by dividing the area under curve by total duration. This gives an estimated average platelet value over the time period from cycles 2 to 6. For 21-Day Cycle, the chemotherapy cycle consisted of 21 days and for 28-Day Cycle, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate thrombocytes at the following time points: 21-Day Cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-Day Cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6.
Time Frame All assessments from Cycle 2 Day 1 to last assessment in Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg) 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Mean (Standard Deviation) [Giga (10^9) cells per liter (G cells/L)]
260.97
(67.581)
307.59
(95.110)
183.68
(55.366)
291.18
(99.718)
12. Secondary Outcome
Title Number of Participants With Thrombocytopenia of Grade 1, 2, 3 or 4 Across All the Chemotherapy Cycles in Phase I, Using Central Laboratory Platelet Count
Description As per the CTCAE version 4.0, par. with a platelet count <LLN but >=75 x 10^9/L (Gi/L) were considered to have Grade 1 thrombocytopenia; par. with a platelet count <75Gi/L, but >=50Gi/L were considered to have Grade 2 thrombocytopenia; par. with a platelet count <50Gi/L, but >=25Gi/L were considered to have Grade 3 thrombocytopenia and par. with a platelet count <25Gi/L were considered to have Grade 4 thrombocytopenia. Blood samples were collected to estimate thrombocytes at the following time points: For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate thrombocytes at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Par. experiencing thrombocytopenia (Platelets <150Gi/L) at least once within a cycle are presented in the category title as n=X,X,X,X.
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Grade 1, n=3,9,4,10
0
0%
2
22.2%
1
25%
3
30%
Grade 2, n=3,9,4,10
0
0%
3
33.3%
1
25%
4
40%
Grade 3, n=3,9,4,10
1
33.3%
1
11.1%
1
25%
0
0%
Grade 4, n=3,9,4,10
1
33.3%
2
22.2%
0
0%
0
0%
Grade 0 / None, n=3,9,4,10
1
33.3%
1
11.1%
1
25%
3
30%
13. Secondary Outcome
Title Maximum Duration of Thrombocytopenia Across Cycles 2 to 6 in Phase I, Estimated Using Central Laboratory Platelet Counts
Description Duration of thrombocytopenia is defined as a period of time in days from the first report of a platelet count with NCI CTCAE Grade 1-4 until the first subsequent report of a platelet count no longer meeting those criteria, regardless of rescue medication usage. It was assessed between Day 1 of Cycle 2 and up to and including any Conclusion/Early Withdrawal visit assigned to the same cycle for participants completing up to 6 cycles, and between Day 1 of Cycle 2 and up to and including the end of Cycle 6 for participants continuing beyond 6 cycles. The chemotherapy cycle for Group A was 21 days and for Group B was 28 days. Blood samples were collected to estimate thrombocytes at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 2 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 2 to 6.
Time Frame Cycle 2 to Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population. Participants experiencing thrombocytopenia with subsequent increase in platelet count to >=150Gi/L are included.
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 2 8 3 7
Mean (Standard Deviation) [Days]
11.0
(4.24)
10.6
(5.63)
14.7
(7.77)
13.4
(5.06)
14. Secondary Outcome
Title Central Laboratory Platelet Count for Time Taken to Reach Platelet Nadir for Each Chemotherapy Cycle in Phase I
Description Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. The time taken to reach platelet nadir is defined within each cycle. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet nadir count at the following time points: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. Group B; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
Cycle 1, n=3,9,4,10
15.7
(0.58)
11.4
(5.53)
13.8
(6.13)
13.8
(4.73)
Cycle 2, n=2,9,4,10
15.0
(1.41)
12.9
(4.68)
14.0
(5.72)
19.2
(4.42)
Cycle 3, n=2,7,2,7
15.0
(1.41)
12.9
(3.02)
23.5
(0.71)
17.6
(4.50)
Cycle 4, n=2,6,1,7
14.0
(0.00)
13.5
(3.33)
14.0
(NA)
17.4
(6.16)
Cycle 5, n=1,2,1,4
15.0
(NA)
11.5
(6.36)
14.0
(NA)
21.5
(1.00)
Cycle 6, n=1,1,1,4
16.0
(NA)
14.0
(NA)
23.0
(NA)
15.5
(5.20)
15. Secondary Outcome
Title Time to Recovery From Platelet Nadir for Each Chemotherapy Cycle in Phase I, Estimated Using Central Laboratory Platelet Counts
Description Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. Time to recovery (TR) (>100Gi/L or >150Gi/L) from platelet nadir is defined within each cycle as the time in days from the platelet nadir to the time at which platelet count returns to >=100Gi/L or >=150Gi/L within the same cycle or up to and including Day 1 of the next cycle. For the last cycle in the study, time to recovery was calculated in the same manner but up to and including any Conclusion/Early Withdrawal visit which has been assigned to the same cycle. For Group A, the chemotherapy cycle consisted of 21 days and for Group B, the chemotherapy cycle consisted of 28 days. Blood samples were collected to estimate platelet count at: Group A; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. Group B; Days 1, 4, 8, 15, 22, and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X, X, X).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
TR(<100Gi/L to >=100Gi/L), Cycle 1, n=3,6,4,7
5.3
(0.58)
7.2
(2.56)
7.0
(0.00)
7.7
(2.87)
TR(<100Gi/L to >=100Gi/L), Cycle 2, n=2,5,3,4
6.5
(2.12)
6.6
(3.65)
6.0
(4.00)
7.0
(5.10)
TR(<100Gi/L to >=100Gi/L), Cycle 3, n=1,4,0,2
7.0
(NA)
8.5
(3.70)
NA
(NA)
6.0
(1.41)
TR(<100Gi/L to >=100Gi/L), Cycle 4, n=1,4,1,2
2.0
(NA)
6.5
(5.20)
14.0
(NA)
5.0
(2.83)
TR(<100Gi/L to >=100Gi/L), Cycle 5, n=1,1,1,1
5.0
(NA)
5.0
(NA)
9.0
(NA)
7.0
(NA)
TR(<100Gi/L to >=100Gi/L), Cycle 6, n=0,1,0,0
NA
(NA)
7.0
(NA)
NA
(NA)
NA
(NA)
TR(<150Gi/L to >=150Gi/L), Cycle 1, n=3,7,4,8
5.3
(0.58)
7.6
(2.57)
7.0
(0.00)
8.5
(3.46)
TR(<150Gi/L to >=150Gi/L), Cycle 2, n=2,4,3,5
6.5
(2.12)
7.8
(2.99)
9.0
(4.36)
9.4
(4.28)
TR(<150Gi/L to >=150Gi/L), Cycle 3, n=1,6,1,5
7.0
(NA)
8.0
(2.97)
7.0
(NA)
6.2
(1.10)
TR(<150Gi/L to >=150Gi/L), Cycle 4, n=1,4,1,4
8.0
(NA)
7.8
(4.27)
14.0
(NA)
8.3
(3.95)
TR(<150Gi/L to >=150Gi/L), Cycle 5, n=1,0,1,3
5.0
(NA)
NA
(NA)
14.0
(NA)
4.7
(2.52)
TR(<150Gi/L to >=150Gi/L), Cycle 6, n=0,0,1,0
NA
(NA)
NA
(NA)
5.0
(NA)
NA
(NA)
16. Secondary Outcome
Title Dose Intensity of Gemcitabine Plus Cisplatin (G+Cis)/Gemcitabine Plus Carboplatin (G+Cb) and Gemcitabine Across Chemotherapy Cycles 1 to 6 in Phase I
Description Dose intensity of chemotherapy is defined as the actual dose of chemotherapy given as a percentage of the scheduled C1D1/C1D8 dose, as applicable, within this study: Cycle Dose Intensity (%) = Total Actual dose (mg/m^2) within Cycle *100/ Total Scheduled dose (mg/m^2) in Cycle 1; wherein Actual Dose (mg/m^2) = Actual dose (mg)/Body Surface Area reported on electronic case report form (eCRF).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 3 9 4 10
G+Cis, Gemcitabine, Cycle 1, n=2,5,0,0
100.0
(0.00)
99.8
(0.45)
NA
(NA)
NA
(NA)
G+Cis, Gemcitabine, Cycle 2, n=1,5,0,0
100.0
(NA)
92.8
(24.83)
NA
(NA)
NA
(NA)
G+Cis, Gemcitabine, Cycle 3, n=1,4,0,0
100.0
(NA)
104.3
(8.50)
NA
(NA)
NA
(NA)
G+Cis, Gemcitabine, Cycle 4, n=1,3,0,0
100.0
(NA)
83.3
(28.87)
NA
(NA)
NA
(NA)
G+Cis, Cisplatin, Cycle 1, n=2,6,0,0
100.0
(0.00)
100.3
(1.03)
NA
(NA)
NA
(NA)
G+Cis, Cisplatin, Cycle 2, n=1,6,0,0
100.0
(NA)
102.8
(6.05)
NA
(NA)
NA
(NA)
G+Cis, Cisplatin, Cycle 3, n=1,5,0,0
100.0
(NA)
93.8
(24.34)
NA
(NA)
NA
(NA)
G+Cis, Cisplatin, Cycle 4, n=1,4,0,0
100.0
(NA)
100.3
(0.96)
NA
(NA)
NA
(NA)
G+Cis, Cisplatin, Cycle 5, n=0,1,0,0
NA
(NA)
50
(NA)
NA
(NA)
NA
(NA)
G+Cb, Gemcitabine, Cycle 1, n=1,2,0,0
99.0
(NA)
100.0
(0.00)
NA
(NA)
NA
(NA)
G+Cb, Gemcitabine, Cycle 2, n=1,2,0,0
99.0
(NA)
88.5
(17.68)
NA
(NA)
NA
(NA)
G+Cb, Gemcitabine, Cycle 3, n=1,2,0,0
99.0
(NA)
100.0
(0.00)
NA
(NA)
NA
(NA)
G+Cb, Gemcitabine, Cycle 4, n=1,2,0,0
49.0
(NA)
99.5
(0.71)
NA
(NA)
NA
(NA)
G+Cb, Gemcitabine, Cycle 5, n=1,1,0,0
99.0
(NA)
74.0
(NA)
NA
(NA)
NA
(NA)
G+Cb, Gemcitabine, Cycle 6, n=1,1,0,0
99.0
(NA)
74.0
(NA)
NA
(NA)
NA
(NA)
G+Cb, Carboplatin, Cycle 1, n=1,3,0,0
101.0
(NA)
88.7
(14.05)
NA
(NA)
NA
(NA)
G+Cb, Carboplatin, Cycle 2, n=1,3,0,0
100.0
(NA)
103.0
(5.20)
NA
(NA)
NA
(NA)
G+Cb, Carboplatin, Cycle 3, n=1,2,0,0
93.0
(NA)
105.0
(5.66)
NA
(NA)
NA
(NA)
G+Cb, Carboplatin, Cycle 4, n=1,2,0,0
91.0
(NA)
107.5
(2.12)
NA
(NA)
NA
(NA)
G+Cb, Carboplatin, Cycle 5, n=1,1,0,0
100.0
(NA)
71.0
(NA)
NA
(NA)
NA
(NA)
G+Cb, Carboplatin, Cycle 6, n=1,1,0,0
87.0
(NA)
79.0
(NA)
NA
(NA)
NA
(NA)
Gemcitabine, Cycle 1, n=0,0,1,7
NA
(NA)
NA
(NA)
100.0
(NA)
94.7
(6.75)
Gemcitabine, Cycle 2, n=0,0,1,7
NA
(NA)
NA
(NA)
100.0
(NA)
85.0
(17.48)
Gemcitabine, Cycle 3, n=0,0,1,4
NA
(NA)
NA
(NA)
100.0
(NA)
79.5
(21.44)
Gemcitabine, Cycle 4, n=0,0,0,4
NA
(NA)
NA
(NA)
NA
(NA)
94.8
(4.11)
Gemcitabine, Cycle 5, n=0,0,0,3
NA
(NA)
NA
(NA)
NA
(NA)
93.7
(3.79)
Gemcitabine, Cycle 6, n=0,0,0,3
NA
(NA)
NA
(NA)
NA
(NA)
72.7
(17.01)
17. Secondary Outcome
Title Number of Participants With at Least One Delay in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase I
Description Any delay in a scheduled dose of gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin was evaluated for eltrombopag and placebo treated participants.
Time Frame All time on chemotherapy treatment

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title 21-Day Cycle Placebo 21-Day Cycle Eltrombopag 100 mg 28-Day Cycle Placebo 28-Day Cycle Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles.
Measure Participants 1 3 4 10
Number [Participants]
1
33.3%
2
22.2%
2
50%
1
10%
18. Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE): Pre-therapy, On-therapy + 30 Days and Post-therapy in Phase II
Description AE is any untoward medical occurrence temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a MP. For marketed MPs, this also includes failure to produce expected benefits, abuse, or misuse. SAE event is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect.
Time Frame From first dose of investigational product (IP) until 30 days after discontinuation of IP (Longer for AEs related to study participation)

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Any AE Pre Therapy
0
0%
1
11.1%
Any SAE Pre Therapy
0
0%
0
0%
Any AE On Therapy+30 days
23
766.7%
48
533.3%
Any SAE On Therapy+30 days
12
400%
16
177.8%
Any AE Post Therapy
4
133.3%
2
22.2%
Any SAE Post Therapy
2
66.7%
1
11.1%
Blood/lymphatic system disorders On-therapy+30 day
21
700%
40
444.4%
Thrombocytopenia On-therapy+30 days
11
366.7%
19
211.1%
Anemia On-therapy+30 days
16
533.3%
26
288.9%
Neutopenia On-therapy+30 days
13
433.3%
21
233.3%
Gastrointestinal disorders On-therapy+30 days
12
400%
25
277.8%
Blood Creatinine increased On-therapy+30 days
3
100%
2
22.2%
Vascular discorders On-therapy+30 days
2
66.7%
6
66.7%
Cardiac disorders On-therapy+30 days
1
33.3%
3
33.3%
Pulmonary embolism On-therapy+30 days
0
0%
1
11.1%
Portal vein thrombosis On-therapy+30 days
1
33.3%
0
0%
Deaths On-therapy+30 days
9
300%
13
144.4%
19. Secondary Outcome
Title Number of Participants With Any Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale, Across Cycles 1-6 in Phase II
Description The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross bleeding; Grade 4=debilitating blood loss. The WHO grades were further classified into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. Baseline is defined as the Day 1 assessment or the latest possible screening assessment. Across Cycles 1-6 included all assessments after first dose of chemotherapy up to the end of Cycle 6. Data exclused for participants taking drugs that affect platelet function or anticoagulants, from the time that the medication was started.
Time Frame Screening, Day -5, Day 1 and 8 of Cycles 1 to 6 of 21-day cycle schedule, Day 1, 8 and 15 of cycles 1 to 6 of 28-day schedule, treatment withdrawal and 30-day follow-up

Outcome Measure Data

Analysis Population Description
ITT Population: Participants with at least one visit within the cycle.
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 12 35
Grade 0
11
366.7%
34
377.8%
Grade 1
1
33.3%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
1
11.1%
20. Secondary Outcome
Title Number of Participants Requiring a Platelet Transfusion in Phase II
Description Platelet transfusion was used as a rescue medication for the treatment of thrombocytopenia. Number of participants requiring a platelet transfusion during Cycles 1-6 was summarized and compared between treatment groups using a logistic regression model adjusted for cycle duration. Each cycle included assessments starting at Day 1 of the cycle.
Time Frame Screening, Day -5, throughout cycles 1 to 6 and up to 30 days after IP discontinuation

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Cycle 1
0
0%
4
44.4%
Cycle 2
2
66.7%
3
33.3%
Cycle 3
0
0%
2
22.2%
Cycle 4
1
33.3%
1
11.1%
Cycle 5
0
0%
0
0%
Cycle 6
0
0%
0
0%
21. Secondary Outcome
Title Number of Participants With at Least One Delay in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase II
Description Any delay in scheduled dose of gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin was evaluated for eltrombopag and placebo treated participants. Number of participants with any delay in dose during 21-day cycle or 28-day cycle, in part 1 or part 2 of the study is summarized and presented. Only those participants who actually received chemotherapy are included for the cisplatin and carboplatin components and all participants are included for the gemcitabine components (represented by n=X,X in the category titles).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Gemcitabine, 21-day cycle, n=11,22
5
166.7%
7
77.8%
Carboplatin, 21-day cycle, n=4,12
4
133.3%
5
55.6%
Cisplatin, 21-day cycle, n=7,9
1
33.3%
2
22.2%
Gemcitabine, 28-day cycle, n=12,30
4
133.3%
4
44.4%
22. Secondary Outcome
Title Number of Participants With Any Dose Reduction in Their Scheduled Dose of Chemotherapy in Any Cycle in Phase II
Description Dose reductions are required following potential drug-related toxicities. Number of participants with any dose reduction during 21-day cycle or 28-day cycle, in part 1 or part 2 of the study is summarized and presented. Only participants who actually received chemotherapy were included for the cisplatin and carboplatin components. All participants were included for the gemcitabine components.
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Gemcitabine, 21-day cycle, n=11,22
7
233.3%
6
66.7%
Carboplatin, 21-day cycle, n=4,12
2
66.7%
2
22.2%
Cisplatin, 21-day cycle, n=7,9
0
0%
3
33.3%
Gemcitabine, 28-day cycle, n=12,30
8
266.7%
8
88.9%
23. Secondary Outcome
Title Dose Intensity of Gemcitabine Plus Cisplatin(G+Cis)/Gemcitabine Plus Carboplatin (G+Cb) and Gemcitabine Across Chemotherapy Cycles 1-6 in Phase II
Description Dose intensity of chemotherapy is defined as the actual dose of chemotherapy given as a percentage of the scheduled C1D1/C1D8 dose, as applicable, within this study: cycle Dose Intensity (%) = Total Actual dose (mg/m^2) within cycle *100/ Total Scheduled dose (mg/m^2) in Cycle 1; wherein Actual Dose (mg/m^2) = Actual dose (mg)/Body Surface Area reported on eCRF. The average chemotherapy dose intensity at Day 1 across Cycles 1 to 6, Day 8 across Cycles 1 to 6 and Day 15 across Cycles 1 to 6 was summarized and compared between treatment groups using an ANCOVA model adjusted for cycle duration and part of the study.
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Cycle 1, n=23,48
96.6
(10.65)
97.9
(6.19)
Cycle 2, n=19,37
113.1
(33.91)
97.8
(24.99)
Cycle 3, n=13,26
102.6
(42.20)
98.7
(35.77)
Cycle 4, n=11,19
96.6
(27.65)
90.7
(30.00)
Cycle 5, n=6,12
102.2
(31.88)
81.3
(25.39)
Cycle 6, n=5,7
84.4
(21.92)
65.2
(25.48)
Cycle 1-6, n=23,49
98.5
(18.26)
94.6
(15.71)
24. Secondary Outcome
Title Number of Participants With Indicated Maximum Toxicity Grades for the Indicated Hematology Parameters, at Anytime Post-Baseline in Phase II
Description Hematology parameters with a related NCI CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment, the maximum toxicity grade reached by a participant post-Baseline was summarized. Hematology parameters included Hemoglobin (Hb) increased, Anemia, Lymphocyte count (Lym), platelet count, White Blood Cell count (WBC) and Total Absolute Neutrophil Count (Total ANC). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. participants with missing Baseline value were assumed to have normal Baseline value. Only those Participant available at the indicated time points were analyzed (represented by n=X,X in the category titles).
Time Frame After baseline (C1D1), on-treatment and 30 day follow-up

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Hb (Increased), Grade 0, n=23,52
23
766.7%
52
577.8%
Hb (Increased), Grade 1, n=23,52
0
0%
0
0%
Hb (Increased), Grade 2, n=23,52
0
0%
0
0%
Hb (Increased), Grade 3, n=23,52
0
0%
0
0%
Hb (Increased), Grade 4, n=23,52
0
0%
0
0%
Hb (Anemia), Grade 0, n=23,52
0
0%
4
44.4%
Hb (Anemia), Grade 1, n=23,52
4
133.3%
16
177.8%
Hb (Anemia), Grade 2, n=23,52
13
433.3%
16
177.8%
Hb (Anemia), Grade 3, n=23,52
6
200%
16
177.8%
Hb (Anemia), Grade 4, n=23,52
0
0%
0
0%
Lym (Increased), Grade 0, n=23,52
22
733.3%
47
522.2%
Lym (Increased), Grade 1, n=23,52
0
0%
0
0%
Lym (Increased), Grade 2, n=23,52
1
33.3%
2
22.2%
Lym (Increased), Grade 3, n=23,52
0
0%
1
11.1%
Lym (Increased), Grade 4, n=23,52
0
0%
0
0%
Lym (Decreased), Grade 0, n=23,52
1
33.3%
7
77.8%
Lym (Decreased), Grade 1, n=23,52
3
100%
10
111.1%
Lym (Decreased), Grade 2, n=23,52
8
266.7%
14
155.6%
Lym (Decreased), Grade 3, n=23,52
9
300%
16
177.8%
Lym (Decreased), Grade 4, n=23,52
2
66.7%
3
33.3%
Total ANC, Grade 0, n=23,52
4
133.3%
16
177.8%
Total ANC, Grade 1, n=23,52
1
33.3%
4
44.4%
Total ANC, Grade2, n=23,52
3
100%
17
188.9%
Total ANC, Grade 3, n=23,52
10
333.3%
10
111.1%
Total ANC, Grade 4, n=23,52
5
166.7%
3
33.3%
Platelet count, Grade 0, n=23,52
0
0%
7
77.8%
Platelet count, Grade 1, n=23,52
4
133.3%
9
100%
Platelet count, Grade 2, n=23,52
3
100%
9
100%
Platelet count, Grade 3, n=23,52
6
200%
15
166.7%
Platelet count, Grade 4, n=23,52
10
333.3%
12
133.3%
WBC count, Grade 0, n=23,52
4
133.3%
14
155.6%
WBC count, Grade 1, n=23,52
3
100%
10
111.1%
WBC count, Grade 2, n=23,52
8
266.7%
17
188.9%
WBC count, Grade 3, n=23,52
6
200%
11
122.2%
WBC count, Grade 4, n=23,52
2
66.7%
0
0%
25. Secondary Outcome
Title Number of Participants With Indicated Worst-case Change From Baseline in Clinical Chemistry Laboratory Parameters Using CTCAE Toxicity Grading, at Anytime Post-Baseline in Phase II
Description Clinical chemistry laboratory parameters with a related CTCAE (version 4.0) toxicity grading were summarized by toxicity grade at each scheduled assessment. Worst-case grade change of the laboratory parameters at anytime post-Baseline is presented as "Any grade increase", "Increase to Grade 3 or Grade 4". Clinical chemistry laboratory parameters included Albumin (Al), creatinine, AST, ALT, ALP, TB, Calcium hypercalcemia (CaHy)/hypocalcemia (CaHo), Glucose hyperglycemia (GluHy)/hypoglycemia (GluHo), Potassium hypernatremia (KHy)/hyponatremia (KHo) and Sodium hypernatremia (NaHy)/hyponatremia (NaHo). The Baseline value is defined as the value reported immediately prior to the administration of the first dose of chemotherapy in Cycle 1. Post-Baseline is defined as any time after the first dose of chemotherapy in Cycle 1 up to and including all follow-up visits. Only those Participant available at the indicated time points were analyzed (represented by n=X,X in the category titles).
Time Frame After baseline (C1D1), on-treatment (collected on days 1 and 8 for subjects on 21-day cycle and on days 1, 8 and 15 for subjects on 28-day cycle) and 30 day follow-up

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Al, Any grade increase, n=23,51
10
333.3%
22
244.4%
Al, Increase to Grade 3, n=23,51
0
0%
2
22.2%
Al, Increase to Grade 4, n=23,51
0
0%
0
0%
ALP, Any grade increase, n=23,52
11
366.7%
16
177.8%
ALP, Increase to Grade 3, n=23,52
1
33.3%
2
22.2%
ALP, Increase to Grade 4, n=23,52
0
0%
0
0%
ALT, Any grade increase, n=23,52
12
400%
16
177.8%
ALT, Increase to Grade 3, n=23,52
3
100%
2
22.2%
ALT, Increase to Grade 4, n=23,52
0
0%
0
0%
AST, Any grade increase, n=23,52
11
366.7%
15
166.7%
AST, Increase to Grade 3, n=23,52
3
100%
2
22.2%
AST, Increase to Grade 4, n=23,52
0
0%
0
0%
TB, Any grade increase, n=23,52
5
166.7%
11
122.2%
TB, Increase to Grade 3, n=23,52
3
100%
2
22.2%
TB, Increase to Grade 4, n=23,52
0
0%
0
0%
CaHy, Any grade increase, n=23,51
0
0%
1
11.1%
CaHy, Increase to Grade 3, n=23,51
0
0%
0
0%
CaHy, Increase to Grade 4, n=23,51
0
0%
0
0%
CaHo, Any grade increase, n=23,51
3
100%
10
111.1%
CaHo, Increase to Grade 3, n=23,51
1
33.3%
2
22.2%
CaHo, Increase to Grade 4, n=23,51
0
0%
0
0%
Creatinine, Any grade increase, n=23,52
5
166.7%
11
122.2%
Creatinine, Increase to Grade 3, n=23,52
1
33.3%
0
0%
Creatinine, Increase to Grade 4, n=23,52
0
0%
0
0%
GluHy, Any grade increase, n=23,52
13
433.3%
31
344.4%
GluHy, Increase to Grade 3, n=23,52
2
66.7%
3
33.3%
GluHy, Increase to Grade 4, n=23,52
0
0%
0
0%
GluHo, Any grade increase, n=23,52
2
66.7%
4
44.4%
GluHo, Increase to Grade 3, n=23,52
0
0%
0
0%
GluHo, Increase to Grade 4, n=23,52
1
33.3%
0
0%
NaHy, Any grade increase, n=23,52
0
0%
2
22.2%
NaHy, Increase to Grade 3, n=23,52
0
0%
0
0%
NaHy, Increase to Grade 4, n=23,52
0
0%
0
0%
NaHo, Any grade increase, n=23,52
4
133.3%
15
166.7%
NaHo, Increase to Grade 3, n=23,52
1
33.3%
1
11.1%
NaHo, Increase to Grade 4, n=23,52
0
0%
0
0%
KHy, Any grade increase, n=23,52
4
133.3%
10
111.1%
KHy, Increase to Grade 3, n=23,52
1
33.3%
1
11.1%
KHy, Increase to Grade 4, n=23,52
0
0%
0
0%
KHo, Any grade increase, n=23,52
5
166.7%
11
122.2%
KHo, Increase to Grade 3, n=23,52
1
33.3%
4
44.4%
KHo, Increase to Grade 4, n=23,52
0
0%
1
11.1%
26. Secondary Outcome
Title Number of Participants With Change From Baseline in Creatinine of >=26.5 UMOL/L in Phase II
Description Number of participants with at least 1 assessment of change from Baseline in creatinine, with increase >=26.5 UMOL/L are presented. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of IP.
Time Frame After baseline (C1D1), on-treatment (collected on days 1 and 8 for subjects on 21-day cycle and on days 1, 8 and 15 for subjects on 28-day cycle) and 30 day follow-up

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Number [participants]
5
166.7%
11
122.2%
27. Secondary Outcome
Title Number of the Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Scores at the Indicated Time Points in Phase II
Description ECOG-Zubrod scores for the Performance Status were defined as follows: 0: Fully active, 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2: Ambulatory and capable of all self-care but unable to carry out any work activities, 3: Capable of only limited self-care, 4: Completely disabled, 5 and Unknown: Dead. The data is presented for the participants with the ECOG performance score at different time points during the study. Only those participants available at the indicated time points were analyzed (represented by n=X,X in the category titles).
Time Frame Screening, C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1 and C17D1

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Screening, Score 0, n=23,52
3
100%
19
211.1%
Screening, Score 1, n=23,52
19
633.3%
32
355.6%
Screening, Score 2, n=23,52
1
33.3%
1
11.1%
C1D1, Score 0, n=23,49
4
133.3%
20
222.2%
C1D1, Score 1, n=23,49
17
566.7%
28
311.1%
C1D1, Score 2, n=23,49
0
0%
1
11.1%
C1D1, Unknown, n=23,49
2
66.7%
0
0%
C2D1, Score 0, n=19,36
4
133.3%
16
177.8%
C2D1, Score 1, n=19,36
13
433.3%
18
200%
C2D1, Score 2, n=19,36
2
66.7%
2
22.2%
C3D1, Score 0, n=13,27
3
100%
9
100%
C3D1, Score 1, n=13,27
9
300%
16
177.8%
C3D1, Score 2, n=13,27
1
33.3%
2
22.2%
C4D1, Score 0, n=11,19
4
133.3%
8
88.9%
C4D1, Score 1, n=11,19
7
233.3%
10
111.1%
C4D1, Score 2, n=11,19
0
0%
1
11.1%
C5D1, Score 0, n=6,12
2
66.7%
5
55.6%
C5D1, Score 1, n=6,12
4
133.3%
6
66.7%
C5D1, Score 2, n=6,12
0
0%
1
11.1%
C6D1, Score 0, n=6,7
2
66.7%
3
33.3%
C6D1, Score 1, n=6,7
4
133.3%
4
44.4%
C7D1, Score 0, n=3,2
1
33.3%
0
0%
C7D1, Score 1, n=3,2
2
66.7%
2
22.2%
C8D1, Score 0, n=2,1
1
33.3%
0
0%
C8D1, Score 1, n=2,1
1
33.3%
1
11.1%
C9D1, Score 1, n=2,1
2
66.7%
1
11.1%
C10D1, Score1 n=2,0
2
66.7%
0
0%
C11D1, Score 1, n=2,0
1
33.3%
0
0%
C11D1, Score 2, n=2,0
1
33.3%
0
0%
C12D1, Score 1, n=2,0
2
66.7%
0
0%
C13D1, Score 0, n=2,0
1
33.3%
0
0%
C13D1, Score 1, n=2,0
1
33.3%
0
0%
C14D1, Score 0, n=2,0
1
33.3%
0
0%
C14D1, Score 1, n=2,0
1
33.3%
0
0%
C15D1, Score 1, n=2,0
2
66.7%
0
0%
C16D1, Score 0, n=1,0
1
33.3%
0
0%
C17D1, Score 2, n=1,0
1
33.3%
0
0%
28. Secondary Outcome
Title Number of Participants With Electrocardiogram (ECG) Findings at Cycle 1 Day 4 (2 to 6 Hours Post-dose) in Phase II
Description A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at screening and 2 to 6 hours post-dose on C1D4. Change in ECG findings were categorized as 'Clinically significant change (CSC): favorable', 'No change or insignificant change' or 'Clinically significant change (CSC): unfavorable' as determined by the investigator. The Baseline value is defined as the value reported immediately prior to the administration of the first dose of investigational product. Only those participants available at the indicated time points were analyzed (represented by n=X,X in the category titles).
Time Frame C1D4

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
CSC favorable, n=22,45
0
0%
2
22.2%
No change or insignificant change, n=22,45
20
666.7%
42
466.7%
CSC: unfavorable, n=22,45
2
66.7%
1
11.1%
29. Secondary Outcome
Title Mean Day 8 Scheduled Pre-chemotherapy Platelet Counts Evaluated Across Cycles 1 to 6 in Phase II
Description Scheduled pre-chemotherapy platelet count is defined within each cycle as the platelet count assessment on which the decision to give or delay chemotherapy was made. This was averaged for each subject across cycles 1 to 6 and a natural log transformation was applied to the average. The log-transformed values were compared between eltrombopag and placebo groups using an analysis of covariance (ANCOVA) model adjusting for cycle duration (21-day vs. 28-day), baseline loge(platelet count) and part of study (part 1 or 2 of phase II). The number of participants analyzed is the number with a Day 8 scheduled platelet count.
Time Frame Day 8 (averaged across cycles 1 to 6)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 20 42
Geometric Mean (Geometric Coefficient of Variation) [Giga (10^9) cells per liter (G cells/L)]
162.18
(74.2)
180.65
(59.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 21-Day Cycle Placebo, 21-Day Cycle Eltrombopag 100 mg
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.407
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Percent difference
Estimated Value 12.9
Confidence Interval (2-Sided) 95%
-15.6 to 51.1
Parameter Dispersion Type:
Value:
Estimation Comments
30. Secondary Outcome
Title Mean Day 15 Scheduled Pre-chemotherapy Platelet Counts Evaluated Across Cycles 1 to 6 in Phase II
Description Scheduled pre-chemotherapy platelet count is defined within each cycle as the platelet count assessment on which the decision to give or delay chemotherapy was made. This was averaged for each subject across cycles 1 to 6 and a natural log transformation was applied to the average. The log-transformed values were compared between eltrombopag and placebo groups using an analysis of covariance (ANCOVA) model adjusting for cycle duration (21-day vs. 28-day), baseline loge(platelet count) and part of study (part 1 or 2 of phase II). The number of participants analyzed is the number with a Day 15 scheduled platelet count.
Time Frame Day 15 (averaged across cycles 1 to 6)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 9 22
Geometric Mean (Geometric Coefficient of Variation) [Giga (10^9) cells per liter (G cells/L)]
95.10
(23.3)
95.29
(52.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 21-Day Cycle Placebo, 21-Day Cycle Eltrombopag 100 mg
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.802
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Percent difference
Estimated Value -4.4
Confidence Interval (2-Sided) 95%
-33.5 to 37.4
Parameter Dispersion Type:
Value:
Estimation Comments
31. Secondary Outcome
Title Mean Within-subject Platelet Count Prior to Scheduled Chemotherapy Across Cycles 1 to 6 in Phase II
Description Within-subject platelet count for each par. was calculated by summing up the visit platelet counts from each of Cycles 1 to 6 and dividing it by the number of cycles in which the par. had data. The average within a treatment group was calculated by summing up the values from each par. within the treatment 21-day cycle dividing it by the number of par. These platelet counts are different from the pre-chemotherapy platelet counts for cycles where the chemotherapy dose was delayed. Average within-subject central laboratory platelet count prior to scheduled chemotherapy across Cycles 1 to 6 are summarized. Blood samples were collected on Day 1 and 8 of Cycles 1 to 6 for 21-day cycle and on Day 1, 8 and 15 from Cycles 1 to 6 for 28-day cycle to estimate the average within subject platelet count prior to scheduled chemotherapy. Only those participants available at the indicated time points were analyzed (represented by n=X,X in the category titles).
Time Frame Day 1, Day 8, Day 15 (all averaged across cycles 1 to 6)

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Day1, n=23,48
221.0
(128.23)
272.9
(120.92)
Day 8, n=20,42
201.0
(143.75)
207.4
(110.93)
Day 15, n=9,22
97.5
(24.82)
106.7
(54.73)
32. Secondary Outcome
Title Platelet Count Nadir for Each Chemotherapy Cycle in Phase II
Description Platelet nadir is defined as the lowest platelet count reported after the first dose of chemotherapy within each cycle. Platelet count nadir is defined for each cycle. Blood samples were collected to estimate platelet nadir count at the following time points: 21-day cycle; Day 1, Day 4, Day 8, Day 15 and Day 17 of Cycles 1 to 6. 28-day cycle; Day 1, Day 4, Day 8, Day 15, Day 22, Day 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Cycle 1, n=23,48
68.3
(47.74)
77.2
(76.43)
Cycle 2, n=19,37
61.5
(35.82)
68.5
(48.92)
Cycle 3, n=13,26
71.6
(53.80)
84.7
(60.03)
Cycle 4, n=11, 19
89.7
(116.73)
86.9
(56.11)
Cycle 5, n=6,11
51.7
(12.23)
83.0
(58.63)
Cycle 6, n=5,5
69.6
(62.76)
136.6
(151.88)
33. Secondary Outcome
Title Average Daily Area Under the Platelet-time Course Across Cycles 1 to 6 in Phase II
Description The average daily area under the platelet-time course was normalized by dividing the area under curve by total duration. This gives an estimated average platelet value over the time period from cycles 1 to 6. Blood samples were collected to estimate platelet count at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6.
Time Frame All assessments from Cycle 1 Day 1 to last assessment in Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population:Participants with platelet count data in at least one cycle in the study.
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 48
Mean (Standard Deviation) [Giga (10^9) cells per liter (G cells/L)]
153.00
(96.079)
189.48
(79.583)
34. Secondary Outcome
Title Number of Participants With Thrombocytopenia of Grade 1, 2, 3 or 4 Across Cycles 1 to 6 in Phase II
Description As per the CTCAE version 4.0, participants with a platelet count <LLN but >=75 x 10^9/L (Gi/L) were considered to have Grade 1 thrombocytopenia; participants with a platelet count <75Gi/L, but >=50Gi/L were considered to have Grade 2 thrombocytopenia; participants with a platelet count <50Gi/L, but >=25Gi/L were considered to have Grade 3 thrombocytopenia and participants with a platelet count <25Gi/L were considered to have Grade 4 thrombocytopenia. Blood samples were collected to estimate thrombocytes at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Participants experiencing thrombocytopenia(Platelets <150Gi/L) at least once within cycle are presented in the category title as n=X,X.
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 50
Grade 1
4
133.3%
9
100%
Grade 2
3
100%
9
100%
Grade 3
8
266.7%
15
166.7%
Grade 4
8
266.7%
12
133.3%
None
0
0%
5
55.6%
35. Secondary Outcome
Title Maximum Duration of Thrombocytopenia Across Cycles 1 to 6 in Phase II
Description Duration of thrombocytopenia is defined as a period of time in days from the first report of a platelet count with NCI CTCAE Grade 1-4 until the first subsequent report of a platelet count no longer meeting those criteria, regardless of rescue medication usage. It was assessed between Day 1 of Cycle 2 and up to and including any Conclusion/Early Withdrawal visit assigned to the same cycle for participants completing up to 6 cycles, and between Day 1 of Cycle 2 and up to and including the end of Cycle 6 for participants continuing beyond 6 cycles. The chemotherapy cycle for 21-day cycle was 21 days and for 28-day cycle was 28 days. Blood samples were collected to estimate thrombocytes at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 2 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 2 to 6.
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population: Participants with at least one period of thrombocytopenia where duration could be calculated.
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 45
Mean (Standard Deviation) [Days]
32.6
(20.31)
23.5
(18.68)
36. Secondary Outcome
Title Time Taken to Reach Platelet Nadir for Each Chemotherapy Cycle in Phase II
Description Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. The time taken to reach platelet nadir is defined within each cycle. Blood samples were collected to estimate platelet nadir count at the following time points: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22 and 24 of Cycles 1 to 6. Only those participants available at indicated time points were analyzed (represented by n=X, X).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
Cycle 1, n=23,48
14.7
(4.85)
15.7
(6.12)
Cycle 2, n=19,37
15.1
(4.41)
15.4
(3.62)
Cycle 3, n=13,26
15.8
(5.64)
14.3
(4.76)
Cycle 4, n=11,19
15.4
(5.48)
14.7
(5.19)
Cycle 5, n=6,11
15.5
(6.38)
13.8
(4.45)
Cycle 6, n=5,5
13.6
(7.37)
10.4
(6.31)
Cycle 7,n=2,2
15.0
(0.00)
7.5
(0.71)
Cycle 8, n=2,1
12.5
(3.54)
8.0
(NA)
Cycle 9, n=2,0
12.5
(3.54)
NA
(NA)
37. Secondary Outcome
Title Time to Recovery From Platelet Nadir for Each Chemotherapy Cycle in Phase II
Description Platelet nadir is defined within each cycle as the lowest platelet count reported after the Day 1 chemotherapy dose. TR (>100Gi/L or >150Gi/L) from platelet nadir is defined within each cycle as the time in days from the platelet nadir to the time at which platelet count returns to >=100Gi/L or >=150Gi/L within the same cycle or up to and including Day 1 of the next cycle. For the last cycle in the study, time to recovery was calculated in the same manner but up to and including any Conclusion/Early Withdrawal visit which has been assigned to the same cycle. Blood samples were collected to estimate platelet count at: 21-day cycle; Days 1, 4, 8, 15 and 17 of Cycles 1 to 6. 28-day cycle; Days 1, 4, 8, 15, 22, and 24of Cycles 1 to 6. Time to recover censored if platelet count did not return to >=100/150 Gi/L. Censored results are excluded from calculation of summary statistics. Only those participants available at indicated time points were analyzed (represented by n=X, X).
Time Frame Cycle 1 to Cycle 6

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag 100 mg
Arm/Group Description Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
Measure Participants 23 52
TR(<100Gi/L to >=100Gi/L), Cycle 1, n=17, 32
8.1
(3.15)
8.5
(3.70)
TR(<150Gi/L to >=150Gi/L), Cycle 1, n=12, 29
9.3
(3.89)
9.1
(3.26)
TR(<100Gi/L to >=100Gi/L), Cycle 2, n=13, 24
9.9
(3.64)
8.3
(2.56)
TR(<150Gi/L to >=150Gi/L), Cycle 2, n=11, 21
10.5
(4.50)
9.0
(3.31)
TR(<100Gi/L to >=100Gi/L), Cycle 3, n=9, 12
10.1
(5.01)
8.8
(3.16)
TR(<150Gi/L to >=150Gi/L), Cycle 3, n=7, 14
10.4
(5.74)
9.6
(3.43)
TR(<100Gi/L to >=100Gi/L), Cycle 4, n=8, 10
10.0
(5.63)
10.9
(4.77)
TR(<150Gi/L to >=150Gi/L), Cycle 4, n=5, 11
10.2
(6.65)
10.6
(5.39)
TR(<100Gi/L to >=100Gi/L), Cycle 5, n=5,6
7.8
(1.10)
8.8
(4.79)
TR(<150Gi/L to >=150Gi/L), Cycle 5, n=2,4
8.0
(0.00)
7.3
(1.50)
TR(<100Gi/L to >=100Gi/L), Cycle 6, n=2,2
10.5
(6.36)
8.5
(0.71)
TR(<150Gi/L to >=150Gi/L), Cycle 6, n=2,1
10.5
(6.36)
8.0
(NA)
TR(<100Gi/L to >=100Gi/L), Cycle 7, n=1,1
15.0
(NA)
22.0
(NA)
TR(<150Gi/L to >=150Gi/L), Cycle 7, n=1,1
15.0
(NA)
22.0
(NA)
TR(<100Gi/L to >=100Gi/L), Cycle 8, n=1,1
14.0
(1.41)
20.0
(NA)
TR(<150Gi/L to >=150Gi/L), Cycle 8, n=1,0
15.0
(NA)
NA
(NA)
TR(<100Gi/L to >=100Gi/L), Cycle 9, n=2,
14.0
(11.31)
NA
(NA)
TR(<150Gi/L to >=150Gi/L), Cycle 9, n=0,
NA
(NA)
NA
(NA)

Adverse Events

Time Frame AEs and SAEs were collected from Cycle 1, Day 1 for Phase I; and from the time the first dose of investigational product (IP) is administered for Phase II; up to 30 days following discontinuation of IP.
Adverse Event Reporting Description
Arm/Group Title Phase I: 21-Day Cycle Placebo Phase I: 21-Day Cycle Eltrombopag Phase I: 28-Day Cycle Placebo Phase I: 28-Day Cycle Eltrombopag 100 mg Phase II: Placebo Phase II: Eltrombopag
Arm/Group Description Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1 and Day 8 plus carboplatin (G+Cb) or cisplatin (G+Cis) on Day 1 (Cis may be divided on Day 1 and Day 8) as a part of the 21-day chemotherapy cycle were administered eltrombopag 100 milligrams (mg) once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine on Day 1, Day 8 and Day 15 as a part of 28-day chemotherapy cycle, were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of Cycle 2 and subsequent chemotherapy cycles. Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle, were administered placebo once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles). Participants receiving gemcitabine plus carboplatin or cisplatin as a part of 21-day chemotherapy cycle or gemcitabine alone as a part of 28-day chemotherapy cycle were administered eltrombopag 100 mg once daily for 5 days before and 5 days after Day 1 of each chemotherapy cycle (up to a maximum of 6 cycles).
All Cause Mortality
Phase I: 21-Day Cycle Placebo Phase I: 21-Day Cycle Eltrombopag Phase I: 28-Day Cycle Placebo Phase I: 28-Day Cycle Eltrombopag 100 mg Phase II: Placebo Phase II: Eltrombopag
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Phase I: 21-Day Cycle Placebo Phase I: 21-Day Cycle Eltrombopag Phase I: 28-Day Cycle Placebo Phase I: 28-Day Cycle Eltrombopag 100 mg Phase II: Placebo Phase II: Eltrombopag
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/3 (33.3%) 5/9 (55.6%) 1/4 (25%) 2/10 (20%) 13/23 (56.5%) 17/52 (32.7%)
Blood and lymphatic system disorders
Anaemia 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 4/52 (7.7%)
Febrile neutropenia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Neutropenia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Pancytopenia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Thrombocytopenia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 2/23 (8.7%) 1/52 (1.9%)
Cardiac disorders
Atrial fibrillation 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Cardiac failure congestive 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Myocardial infarction 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Gastrointestinal disorders
Diarrhoea 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Intestinal obstruction 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Nausea 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Oesophageal varices haemorrhage 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Small intestinal obstruction 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Vomiting 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
General disorders
General physical health deterioration 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Device damage 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 0/52 (0%)
Hepatobiliary disorders
Cholecystitis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Cholestasis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Hepatic function abnormal 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Jaundice 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 2/52 (3.8%)
Jaundice cholestatic 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Cholangitis 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 0/52 (0%)
Immune system disorders
Hypersensitivity 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Infections and infestations
Arthritis infective 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Bacterial sepsis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Cellulitis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Diverticulitis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Pneumonia 1/3 (33.3%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 3/52 (5.8%)
Respiratory tract infection 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Sepsis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Tracheobronchitis 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Viral infection 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Investigations
Alanine aminotransferase increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 1/23 (4.3%) 0/52 (0%)
Aspartate aminotransferase increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Blood alkaline phosphatase increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Blood bilirubin increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 2/23 (8.7%) 0/52 (0%)
Platelet count decreased 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 0/52 (0%)
Metabolism and nutrition disorders
Dehydration 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 2/52 (3.8%)
Nervous system disorders
Hypoglycaemic coma 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Seizure cluster 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 0/23 (0%) 0/52 (0%)
Psychiatric disorders
Confusional state 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Renal and urinary disorders
Calculus urinary 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Renal failure acute 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 2/23 (8.7%) 0/52 (0%)
Oliguria 0/3 (0%) 0/9 (0%) 1/4 (25%) 0/10 (0%) 0/23 (0%) 0/52 (0%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 1/52 (1.9%)
Pleural effusion 0/3 (0%) 0/9 (0%) 1/4 (25%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Pneumonitis 1/3 (33.3%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Pulmonary embolism 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Haemoptysis 1/3 (33.3%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 0/52 (0%)
Skin and subcutaneous tissue disorders
Petechiae 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 0/52 (0%)
Rash maculo-papular 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 1/52 (1.9%)
Vascular disorders
Deep vein thrombosis 0/3 (0%) 2/9 (22.2%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 0/52 (0%)
Other (Not Including Serious) Adverse Events
Phase I: 21-Day Cycle Placebo Phase I: 21-Day Cycle Eltrombopag Phase I: 28-Day Cycle Placebo Phase I: 28-Day Cycle Eltrombopag 100 mg Phase II: Placebo Phase II: Eltrombopag
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/3 (100%) 9/9 (100%) 4/4 (100%) 10/10 (100%) 22/23 (95.7%) 47/52 (90.4%)
Blood and lymphatic system disorders
Anaemia 1/3 (33.3%) 4/9 (44.4%) 3/4 (75%) 5/10 (50%) 15/23 (65.2%) 24/52 (46.2%)
Leukopenia 2/3 (66.7%) 2/9 (22.2%) 2/4 (50%) 3/10 (30%) 2/23 (8.7%) 9/52 (17.3%)
Lymphopenia 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 5/23 (21.7%) 7/52 (13.5%)
Neutropenia 3/3 (100%) 5/9 (55.6%) 2/4 (50%) 6/10 (60%) 13/23 (56.5%) 21/52 (40.4%)
Thrombocytopenia 3/3 (100%) 3/9 (33.3%) 4/4 (100%) 5/10 (50%) 10/23 (43.5%) 18/52 (34.6%)
Thrombocytosis 2/3 (66.7%) 2/9 (22.2%) 1/4 (25%) 2/10 (20%) 2/23 (8.7%) 4/52 (7.7%)
Gastrointestinal disorders
Abdominal pain 0/3 (0%) 1/9 (11.1%) 1/4 (25%) 1/10 (10%) 3/23 (13%) 7/52 (13.5%)
Abdominal pain upper 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 4/52 (7.7%)
Constipation 0/3 (0%) 4/9 (44.4%) 0/4 (0%) 1/10 (10%) 4/23 (17.4%) 4/52 (7.7%)
Diarrhoea 1/3 (33.3%) 0/9 (0%) 1/4 (25%) 1/10 (10%) 4/23 (17.4%) 5/52 (9.6%)
Dry mouth 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 4/52 (7.7%)
Dyspepsia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 0/23 (0%) 5/52 (9.6%)
Nausea 1/3 (33.3%) 6/9 (66.7%) 1/4 (25%) 1/10 (10%) 2/23 (8.7%) 10/52 (19.2%)
Vomiting 1/3 (33.3%) 1/9 (11.1%) 0/4 (0%) 3/10 (30%) 3/23 (13%) 5/52 (9.6%)
General disorders
Asthenia 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 4/23 (17.4%) 8/52 (15.4%)
Fatigue 1/3 (33.3%) 1/9 (11.1%) 2/4 (50%) 3/10 (30%) 3/23 (13%) 13/52 (25%)
Oedema peripheral 0/3 (0%) 1/9 (11.1%) 2/4 (50%) 2/10 (20%) 1/23 (4.3%) 5/52 (9.6%)
Pain 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 2/52 (3.8%)
Peripheral swelling 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 5/23 (21.7%) 3/52 (5.8%)
Pyrexia 1/3 (33.3%) 1/9 (11.1%) 2/4 (50%) 0/10 (0%) 4/23 (17.4%) 3/52 (5.8%)
Infections and infestations
Bronchitis 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 5/23 (21.7%) 0/52 (0%)
Investigations
Alanine aminotransferase increased 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 5/52 (9.6%)
Aspartate aminotransferase increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 3/52 (5.8%)
Blood alkaline phosphatase increased 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 2/10 (20%) 3/23 (13%) 4/52 (7.7%)
Blood bilirubin increased 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 1/10 (10%) 1/23 (4.3%) 3/52 (5.8%)
Blood creatinine increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 3/23 (13%) 2/52 (3.8%)
Lymphocyte count decreased 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 3/23 (13%) 6/52 (11.5%)
Neutrophil count decreased 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 3/23 (13%) 3/52 (5.8%)
Platelet count decreased 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 5/23 (21.7%) 6/52 (11.5%)
White blood cell count decreased 0/3 (0%) 0/9 (0%) 0/4 (0%) 3/10 (30%) 3/23 (13%) 4/52 (7.7%)
Platelet count increased 0/3 (0%) 0/9 (0%) 0/4 (0%) 3/10 (30%) 1/23 (4.3%) 1/52 (1.9%)
Metabolism and nutrition disorders
Decreased appetite 0/3 (0%) 1/9 (11.1%) 1/4 (25%) 2/10 (20%) 6/23 (26.1%) 7/52 (13.5%)
Diabetes mellitus 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 3/23 (13%) 1/52 (1.9%)
Hypocalcaemia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 4/52 (7.7%)
Hypokalaemia 0/3 (0%) 1/9 (11.1%) 1/4 (25%) 1/10 (10%) 1/23 (4.3%) 7/52 (13.5%)
Hyperglycamia 1/3 (33.3%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 2/52 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 5/23 (21.7%) 2/52 (3.8%)
Back pain 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 2/23 (8.7%) 7/52 (13.5%)
Musculoskeletal chest pain 0/3 (0%) 0/9 (0%) 0/4 (0%) 0/10 (0%) 2/23 (8.7%) 0/52 (0%)
Pain in extremity 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 1/23 (4.3%) 5/52 (9.6%)
Nervous system disorders
Dizziness 0/3 (0%) 0/9 (0%) 2/4 (50%) 1/10 (10%) 2/23 (8.7%) 1/52 (1.9%)
Polyneuropathy 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 2/23 (8.7%) 1/52 (1.9%)
headache 0/3 (0%) 2/9 (22.2%) 1/4 (25%) 2/10 (20%) 1/23 (4.3%) 2/52 (3.8%)
Psychiatric disorders
Depression 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 0/10 (0%) 1/23 (4.3%) 4/52 (7.7%)
Insomnia 0/3 (0%) 2/9 (22.2%) 2/4 (50%) 0/10 (0%) 4/23 (17.4%) 4/52 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 2/52 (3.8%)
Dyspnoea 1/3 (33.3%) 1/9 (11.1%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 5/52 (9.6%)
Epistaxis 0/3 (0%) 1/9 (11.1%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 1/52 (1.9%)
Productive cough 0/3 (0%) 0/9 (0%) 0/4 (0%) 1/10 (10%) 2/23 (8.7%) 1/52 (1.9%)
Skin and subcutaneous tissue disorders
Alopecia 0/3 (0%) 0/9 (0%) 1/4 (25%) 1/10 (10%) 1/23 (4.3%) 0/52 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01147809
Other Study ID Numbers:
  • 112765
First Posted:
Jun 22, 2010
Last Update Posted:
Apr 18, 2016
Last Verified:
Mar 1, 2016