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This was a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Chinese subjects with refractory or relapsed severe aplastic anemia (SAA). Treatment with eltrombopag was started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day. The hematological response rate was assessed at 3, 6 months and 1 year after starting the study treatment (Week 13, 26 and 52).
This was a bridging study to support China registration. An estimation strategy rather than a formal hypothesis testing was pursued. Twenty subjects were enrolled into the study.
Treatment with eltrombopag started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count, up to 150 mg/day. Hematological response rate was assessed at 3, 6 months and 1 year (Week 13, 26 and 52) after starting the study treatment. Subjects in whom the treatment was found to be effective at 6 months continued to receive the treatment. Eltrombopag was discontinued if the treatment was ineffective at 6 months. Subjects discontinued eltrombopag before 6 months if any of the treatment discontinuation criteria was met.
Analysis set for the primary endpoint was Full Analysis Set (FAS) and subjects who discontinue from the study before Week 26 were treated as non-responders in the response analysis. Eltrombopag treatment was provided to subjects who were considered to require continued treatment at Week 26. After Week 26, if all of the hematologic response criteria (i.e., platelet count > 50×109/L, hemoglobin level > 100 g/L without transfusion, and neutrophil count > 1.0×109/L) remained fulfilled for more than 8 weeks, the dose of eltrombopag was decreased by half. If the response continued for further 8 weeks even at the decreased dose, the treatment was discontinued. If a decrease in any of the hematologic values (i.e., platelet count < 30×109/L, hemoglobin < 90 g/L, or neutrophil count < 0.5×109/L) was found after dose reduction, the dose was increased to the previous level. Furthermore, after treatment interruption, the treatment was restarted if any of the hematologic values decreased to the above-mentioned levels. The response assessment and safety evaluation were performed at Week 52.
The Extension part of this study started 1 year (Week 52) after the initiation of study treatment. This part was included in the study with an ethical consideration for subjects who required continued treatment. The continued treatment was provided up to the launch of eltrombopag after approval. Follow-up visit was performed 30 days after the discontinuation of eltrombopag treatment.
To better understand the pharmacokinetics (PK) characteristics of eltrombopag in Chinese severe aplastic anemia (SAA) patient population, intensive PK blood samples were collected only in the initial 12 Chinese subjects receiving 25 mg/day dose after reaching steady-state, to provide evaluable full PK profiles. Steady-state trough concentrations were collected at other dose levels and in other subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eltrombopag | Experimental | Subjects started eltrombopag treatment at 25 mg/day since Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eltrombopag | Drug | Eltrombopag are film-coated tablets containing 25 mg of eltrombopag free acid in each tablet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hematologic Response Rate at 6 Months (Week 26) by Investigator | Hematologic response rate: percentage of subjects who met any of the International Working Group criteria: Platelet count: If platelet transfusion independent at baseline (BL): Transfusion independent and increase from BL by 20×10^9/L or more; If platelet transfusion dependent at BL: No platelet transfusion requirement for 8 weeks; Hemoglobin: If red blood cells (RBC) transfusion independent at BL: transfusion independent and increase from BL by 15 g/L or more; If RBC transfusion dependent at BL: A decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period (1 unit = RBC derived from 200 mL blood) or no RBC transfusion requirement for 8 weeks; Neutrophil count: In the absence of granulocyte colony stimulating factor (G-CSF) taken within 21 days preceding the blood sample collection: Increase from BL by 0.5×10^9/L or more, or (if < 0.5×10^9/L at BL) increase by 100% or more. Patients who discontinued from the trial before week 26 were treated as non-responders. | 6 months (Week 26) |
| Measure | Description | Time Frame |
|---|---|---|
| Hematologic Response Rate by Investigator | Hematologic response rate: percentage of subjects who met any of the International Working Group criteria: Platelet count: If platelet transfusion independent at baseline (BL): Transfusion independent and increase from BL by 20×10^9/L or more; If platelet transfusion dependent at BL: No platelet transfusion requirement for 8 wks; Hemoglobin: If red blood cells (RBC) transfusion independent at BL: transfusion independent and increase from BL by 15 g/L or more; If RBC transfusion dependent at BL: A decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period (1 unit =RBC derived from 200 mL blood) or no RBC transfusion requirement for 8 wks; Neutrophil count: In the absence of granulocyte colony stimulating factor (G-CSF) taken within 21 days preceding the blood sample collection: Increase from BL by 0.5×10^9/L or more, or (if < 0.5×10^9/L at BL) increase by 100% or more. Patients who discontinued from the trial before wks 13 & 26 were treated as non-responders. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Nanjing | Jiangsu | 210000 | China | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37919313 | Derived | Chang H, He G, Fu R, Li F, Han B, Li T, Liu L, Mittal H, Jin H, Zhang F. Efficacy and safety of eltrombopag in Chinese patients with refractory or relapsed severe aplastic anemia. Sci Rep. 2023 Nov 2;13(1):18955. doi: 10.1038/s41598-023-45607-0. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com
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One of the main criteria for enrollment was for Chinese patients aged ≥ 18 years, previously diagnosed with SAA and who had insufficient response following at least one treatment course in the period time of > 6 months of immunosuppression with a regimen containing anti-thymocyte globulin (ATG), anti-lymphocyte Immunoglobulin (ALG), and/or cyclophosphamide, or alemtuzumab.
The study enrolled all 20 participants from 5 sites in China.
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| ID | Title | Description |
|---|---|---|
| FG000 | Eltrombopag | Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Eltrombopag | Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hematologic Response Rate at 6 Months (Week 26) by Investigator | Hematologic response rate: percentage of subjects who met any of the International Working Group criteria: Platelet count: If platelet transfusion independent at baseline (BL): Transfusion independent and increase from BL by 20×10^9/L or more; If platelet transfusion dependent at BL: No platelet transfusion requirement for 8 weeks; Hemoglobin: If red blood cells (RBC) transfusion independent at BL: transfusion independent and increase from BL by 15 g/L or more; If RBC transfusion dependent at BL: A decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period (1 unit = RBC derived from 200 mL blood) or no RBC transfusion requirement for 8 weeks; Neutrophil count: In the absence of granulocyte colony stimulating factor (G-CSF) taken within 21 days preceding the blood sample collection: Increase from BL by 0.5×10^9/L or more, or (if < 0.5×10^9/L at BL) increase by 100% or more. Patients who discontinued from the trial before week 26 were treated as non-responders. | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. The patients who discontinued from the trial before Week 26 were treated as non-responders. | Posted | Number | 90% Confidence Interval | Percentage of participants | 6 months (Week 26) |
Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period.
Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eltrombopag (On-treatment) | Safety data collected from first dose of study medication up to 30 days after last dose. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | MedDRA (26.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Disclosure Office | Novartis Pharmaceuticals | 862-778-3000 | novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 2, 2019 | May 9, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 22, 2023 | May 9, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000741 | Anemia, Aplastic |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000080983 | Bone Marrow Failure Disorders |
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| ID | Term |
|---|---|
| C520809 | eltrombopag |
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| Week (Wk) 13, Week 52 |
| Change From Baseline in Platelet Count | Change (increase from baseline) in platelet count (in the absence of platelet transfusion) were calculated according to the lab test results entered into the case report form (CRF) that were summarized at each visit using descriptive statistics. Platelet Count (×109/L) was assessed in hematology test. | Baseline, Week 13, Week 26, Week 52 |
| Change From Baseline in Hemoglobin Levels | Change (increase from baseline) in hemoglobin (in the absence of red blood cell (RBC) transfusion) were calculated according to the lab test results entered into the CRF that were summarized at each visit using descriptive statistics. Hemoglobin level (g/L) was assessed in hematology test. | Baseline, Week 13, Week 26 and Week 52 |
| Change From Baseline in Neutrophil Count | Change (increase from baseline) in neutrophil count (in the absence of granulocyte colony stimulating factor (G-CSF) and calculated according to the lab test results entered into the CRF that were summarized at each visit using descriptive statistics). Neutrophil count (×109/L) was assessed in hematology test. | Baseline, Week 13, Week 26 and Week 52 |
| Time to Hematologic Response by Investigator | Time to hematological response was defined as the time from the date of first study drug administration to the first hematological response. If a participant did not meet hematological response before or at the cutoff date, censoring was performed using the date of last assessment. | Baseline to Week 26 |
| Duration of Hematologic Response by Investigator | Duration of hematologic response (any response according to the response criteria for the primary endpoint). For subjects who responded, duration of response was defined as the number of weeks from the first date of hematological response until the first date of relapse or death. Only participants with at least two response assessments were included for the duration of hematologic response assessment. | up to approx. 3.5 years |
| Frequency of Platelets Transfusion | For subjects receiving transfusion (platelets) at baseline, the frequency of platelet transfusion in each period (Baseline: 4 weeks before Day 1; Week 13, 26, 52: 4 weeks before each visit day) was summarized using descriptive statistics. | Baseline, Week 13, Week 26 and Week 52 |
| Amount of Platelets Transfusion | The amount of transfusion was defined as the sum of transfusion multiplied by the volume of transfusion. | Baseline, Week 13, Week 26 and Week 52 |
| Frequency of Red Blood Cells (RBC) Transfusion | For subjects receiving transfusion (RBC (Red Blood Cell)) at baseline, the frequency of RBC transfusion in each period (Baseline: 8 weeks before Day 1; Week 13, 26, 52: 8 weeks before each visit day) was summarized using descriptive statistics. | Baseline, Week 13, Week 26 and Week 52 |
| Amount of Red Blood Cells (RBC) Transfusion | The amount of RBC transfusion was defined as the sum of transfusion multiplied by the volume of transfusion. | Baseline, Week 13, Week 26 and Week 52 |
| Plasma PK Parameters of Eltrombopag: Cmax | Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass*volume-1). Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
| Plasma PK Parameters of Eltrombopag: Tmax | Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time). Blood samples were collected from all patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
| Plasma PK Parameters of Eltrombopag: AUCtau & AUClast | AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state (amount*time*volume-1). AUClast is the AUC calculated from time 0 to the time of the last quantifiable concentration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
| Plasma PK Parameters of Eltrombopag: CLss/F | Steady State (CLss/F) is the apparent systemic (or total body) clearance at steady state from plasma (volume/time) following drug administration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
| Plasma Trough Concentration of Eltrombopag | Ctrough is the pre-dose concentration at the end of dose interval (mass*volume-1). Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. Sparse PK blood samples were collected for the other doses and in the rest of the patients for Ctrough assessment. | Pre-dose sample on the 15th day after each new dose level was started |
| Number of Participants With Clonal Evolution | Number of participants with clonal evolution with a normal karyotype at baseline including clonal evolution to PNH (Paroxysmal Nocturnal Hemoglobinuria), evolution to AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes). | From Baseline up to approx. 2.9 years |
| Nanchang |
| Jiangxi |
| 330006 |
| China |
| Novartis Investigative Site | Chengdu | Sichuan | 610041 | China |
| Novartis Investigative Site | Tianjin | 300020 | China |
| Novartis Investigative Site | Tianjin | 300052 | China |
| Death |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
|
|
|
| Secondary | Hematologic Response Rate by Investigator | Hematologic response rate: percentage of subjects who met any of the International Working Group criteria: Platelet count: If platelet transfusion independent at baseline (BL): Transfusion independent and increase from BL by 20×10^9/L or more; If platelet transfusion dependent at BL: No platelet transfusion requirement for 8 wks; Hemoglobin: If red blood cells (RBC) transfusion independent at BL: transfusion independent and increase from BL by 15 g/L or more; If RBC transfusion dependent at BL: A decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period (1 unit =RBC derived from 200 mL blood) or no RBC transfusion requirement for 8 wks; Neutrophil count: In the absence of granulocyte colony stimulating factor (G-CSF) taken within 21 days preceding the blood sample collection: Increase from BL by 0.5×10^9/L or more, or (if < 0.5×10^9/L at BL) increase by 100% or more. Patients who discontinued from the trial before wks 13 & 26 were treated as non-responders. | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. | Posted | Number | 90% Confidence Interval | Percentage of participants | Week (Wk) 13, Week 52 |
|
|
|
| Secondary | Change From Baseline in Platelet Count | Change (increase from baseline) in platelet count (in the absence of platelet transfusion) were calculated according to the lab test results entered into the case report form (CRF) that were summarized at each visit using descriptive statistics. Platelet Count (×109/L) was assessed in hematology test. | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. These were the patients in FAS with a valid assessment for the outcome measure at baseline and at Weeks 13, 26 and 52. | Posted | Mean | Standard Deviation | 10^9 platelets/liter | Baseline, Week 13, Week 26, Week 52 |
|
|
|
| Secondary | Change From Baseline in Hemoglobin Levels | Change (increase from baseline) in hemoglobin (in the absence of red blood cell (RBC) transfusion) were calculated according to the lab test results entered into the CRF that were summarized at each visit using descriptive statistics. Hemoglobin level (g/L) was assessed in hematology test. | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. These were the patients in FAS with a valid assessment for the outcome measure at baseline and at Weeks 13, 26 and 52. | Posted | Mean | Standard Deviation | gram/liter | Baseline, Week 13, Week 26 and Week 52 |
|
|
|
| Secondary | Change From Baseline in Neutrophil Count | Change (increase from baseline) in neutrophil count (in the absence of granulocyte colony stimulating factor (G-CSF) and calculated according to the lab test results entered into the CRF that were summarized at each visit using descriptive statistics). Neutrophil count (×109/L) was assessed in hematology test. | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. These were the patients in FAS with a valid assessment for the outcome measure at baseline and at Weeks 13, 26 and 52. | Posted | Mean | Standard Deviation | 10^9 neutrophils/liter | Baseline, Week 13, Week 26 and Week 52 |
|
|
|
| Secondary | Time to Hematologic Response by Investigator | Time to hematological response was defined as the time from the date of first study drug administration to the first hematological response. If a participant did not meet hematological response before or at the cutoff date, censoring was performed using the date of last assessment. | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment and achieved a hematologic response. | Posted | Median | 90% Confidence Interval | Weeks | Baseline to Week 26 |
|
|
|
| Secondary | Duration of Hematologic Response by Investigator | Duration of hematologic response (any response according to the response criteria for the primary endpoint). For subjects who responded, duration of response was defined as the number of weeks from the first date of hematological response until the first date of relapse or death. Only participants with at least two response assessments were included for the duration of hematologic response assessment. | Participants in the FAS who achieved a hematologic response. The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment and achieved a hematologic response. | Posted | Median | 90% Confidence Interval | Weeks | up to approx. 3.5 years |
|
|
|
| Secondary | Frequency of Platelets Transfusion | For subjects receiving transfusion (platelets) at baseline, the frequency of platelet transfusion in each period (Baseline: 4 weeks before Day 1; Week 13, 26, 52: 4 weeks before each visit day) was summarized using descriptive statistics. | Participants in the FAS who were platelet transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52). | Posted | Mean | Standard Deviation | occurrences | Baseline, Week 13, Week 26 and Week 52 |
|
|
|
| Secondary | Amount of Platelets Transfusion | The amount of transfusion was defined as the sum of transfusion multiplied by the volume of transfusion. | Participants in the FAS who were platelet transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52). | Posted | Mean | Standard Deviation | Units | Baseline, Week 13, Week 26 and Week 52 |
|
|
|
| Secondary | Frequency of Red Blood Cells (RBC) Transfusion | For subjects receiving transfusion (RBC (Red Blood Cell)) at baseline, the frequency of RBC transfusion in each period (Baseline: 8 weeks before Day 1; Week 13, 26, 52: 8 weeks before each visit day) was summarized using descriptive statistics. | Participants in the FAS who were RBC transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52). | Posted | Mean | Standard Deviation | occurrences | Baseline, Week 13, Week 26 and Week 52 |
|
|
|
| Secondary | Amount of Red Blood Cells (RBC) Transfusion | The amount of RBC transfusion was defined as the sum of transfusion multiplied by the volume of transfusion. | Participants in the FAS who were RBC transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52). | Posted | Mean | Standard Deviation | Units | Baseline, Week 13, Week 26 and Week 52 |
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|
|
| Secondary | Plasma PK Parameters of Eltrombopag: Cmax | Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass*volume-1). Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | Participants in the pharmacokinetic analysis set (PAS) who had an evaluable pharmacokinetic (PK) profile at steady state. The pharmacokinetic analysis set (PAS) included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample. | Posted | Mean | Standard Deviation | ng/mL | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
|
|
|
| Secondary | Plasma PK Parameters of Eltrombopag: Tmax | Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time). Blood samples were collected from all patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | Participants in the pharmacokinetic analysis set (PAS) who had an evaluable pharmacokinetic (PK) profile at steady state. The pharmacokinetic analysis set (PAS) included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample. | Posted | Median | Full Range | hour | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
|
|
|
| Secondary | Plasma PK Parameters of Eltrombopag: AUCtau & AUClast | AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state (amount*time*volume-1). AUClast is the AUC calculated from time 0 to the time of the last quantifiable concentration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | Participants in the pharmacokinetic analysis set (PAS) who had an evaluable pharmacokinetic (PK) profile at steady state. The pharmacokinetic analysis set (PAS) included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample. | Posted | Mean | Standard Deviation | h*ng/mL | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
|
|
|
| Secondary | Plasma PK Parameters of Eltrombopag: CLss/F | Steady State (CLss/F) is the apparent systemic (or total body) clearance at steady state from plasma (volume/time) following drug administration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. | Participants in the pharmacokinetic analysis set (PAS) who had an evaluable PK profile at steady state and who had a valid value for the outcome measure. The PAS included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample. | Posted | Mean | Standard Deviation | L/h | pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14 |
|
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| Secondary | Plasma Trough Concentration of Eltrombopag | Ctrough is the pre-dose concentration at the end of dose interval (mass*volume-1). Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. Sparse PK blood samples were collected for the other doses and in the rest of the patients for Ctrough assessment. | The pharmacokinetic analysis set (PAS) included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose sample on the 15th day after each new dose level was started |
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| Secondary | Number of Participants With Clonal Evolution | Number of participants with clonal evolution with a normal karyotype at baseline including clonal evolution to PNH (Paroxysmal Nocturnal Hemoglobinuria), evolution to AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes). | The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned. | Posted | Count of Participants | Participants | From Baseline up to approx. 2.9 years |
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| Post-Hoc | All Collected Deaths | Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. | All enrolled participants. | Posted | Number | Participants | On-treatment deaths: up to approx. 3.5 years, post-treatment deaths: up to approx. 3.5 years |
|
|
|
| 0 |
| 20 |
| 8 |
| 20 |
| 19 |
| 20 |
| EG001 | Eltrombopag (Post-treatment) | Deaths collected from 31 days after last dose of study medication up to end of study. These are not considered adverse events. | 1 | 20 | 0 | 0 | 0 | 0 |
| Gastritis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
|
| Liver injury | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
| Spermatic cord funiculitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
| Intentional product misuse | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
|
| Abnormal uterine bleeding | Reproductive system and breast disorders | MedDRA (26.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (26.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
|
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
|
| Liver injury | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Electrocardiogram T wave abnormal | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (26.0) | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Iron overload | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in clinical trial or disclosure of trial results in their entirety.
| D001855 | Bone Marrow Diseases |
|
| Change from BL at Week 26/Day 183 |
|
|
| Change from BL at Week 52/Day 365 |
|
|
|
| Change from baseline at Week 26/Day 183 |
|
|
| Change from BL at Week 52/Day 365 |
|
|
|
| Change from baseline at Week 26/Day 183 (n = 14) |
|
|
| Change from BL at Week 52/Day 365 (n = 14) |
|
|
|
| Week 26 |
|
|
| Week 52 |
|
|
|
| Week 26 |
|
|
| Week 52 |
|
|
|
| Week 26 |
|
|
| Week 52 |
|
|
|
| Week 25 |
|
|
| Week 52 |
|
|
|
|
| concentration at 75 mg |
|
|
| concentration at 100 mg |
|
|
| concentration at 125 mg |
|
|
| concentration at 150 mg |
|
|
| Title | Measurements |
|---|---|
|