ASPIRE: A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01440374
Collaborator
(none)
162
120
4
51
1.4
0
Study Details
Study Description
Brief Summary
This was a worldwide, three-part (Part 1: open-label, Part 2: randomized, double-blind, Part 3: extension), multi-center study to evaluate the effect of eltrombopag in subjects with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who have thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy. This objective was assessed by a composite primary endpoint that consists of the following: the proportion of ≥Grade 3 hemorrhagic adverse events, or platelet counts <10 Gi/L, or platelet transfusions. Patients with MDS or AML and Grade 4 thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy were enrolled in the study. No low or intermediate-1 risk MDS subjects were enrolled in the study. Subjects must have had at least one of the following during the 4 weeks prior to enrolment: platelet count <10 Gi/L, platelet transfusion, or symptomatic hemorrhagic event. Supportive standard of care (SOC), including hydroxyurea, was allowed as indicated by local practice throughout the study. The study had 3 sequential parts. Subjects who were enrolled in Part 1 (open-label) cannot be enrolled in Part 2 of the study (randomized, double-blind); however, subjects who completed the treatment period for Part 1 or Part 2 (8 and 12 weeks, respectively) continued in Part 3 (extension) if the investigator determined that the subject was receiving clinical benefit on treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
162 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
Official Title:
A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia (Part 1: Open-label, Part 2: Randomized, Double-blind, Part 3: Extension)
Study Start Date
:
Sep 1, 2011
Actual Primary Completion Date
:
Mar 1, 2015
Actual Study Completion Date
:
Dec 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1, Open Label 100 mg daily (50 mg for subjects of East Asian heritage), intrasubject dose escalations to a maximum dose 300 mg (150 mg for subjects of East Asian heritage) are allowed. |
Drug: eltrombopag
100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
Other Names:
|
| Experimental: Part 2, eltrombopag arm 100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage) |
Drug: eltrombopag
100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
Other Names:
|
| Experimental: Part 2, placebo arm 100 mg matching placebo daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg matching placebo (150 mg for subjects of East Asian heritage) |
Drug: placebo
100 mg matching placebo daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg matching placebo (150 mg for subjects of East Asian heritage)
|
| Experimental: part 3 extension 100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage) |
Drug: eltrombopag
100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Platelet Response up to Week 8 During Part 1 [From Baseline up to Week 8 during Part 1]
A participant was considered as a responder if he/she met the following response criteria: a Baseline platelet count <20 Giga cells per liter (Gi/L) and a post-Baseline increased to >20 Gi/L and at least 2 times the Baseline value; or a Baseline platelet count >=20 Gi/L and a post-Baseline absolute platelet count increased to >=50 Gi/L and at least 2 times the Baseline value. The response criteria was evaluated at each visit. Increase in platelet count observed up to 3 days after a platelet transfusion was not considered as a platelet response. The Part 1 Population was comprised of all participants enrolled into Part 1.
- Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2 [From Week 5 up to Week 12 during Part 2]
A participant was considered to have a CRTE at a given assessment if he/she had platelet counts <10 Gi/L, or platelet transfusions, or >=Grade 3 hemorrhagic adverse events. CRTEs during Weeks 5 to 12 were compared between treatments using a generalized linear mixed model. Average of weekly proportion of subjects with CRTE during Week 5 to 12 was estimated for each treatment. Intent to Treat (ITT) Population was comprised of all randomized participants during Part 2.
Secondary Outcome Measures
- Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) [Day 1 to week 8]
- Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) [Day 1 to week 12]
- Mean Number of Platelet Transfusions [Weeks 5 to 12]
- Hematologic Improvement [Weeks 5 to 12]
Definitions of hematologic improvement for platelets, neutrophils, and hemoglobin were based on modified International Working Group (IWG) consensus criteria.
- Change in Mean Platelet Count [Baseline to Week 12]
- Maximum Duration of Platelet Transfusion Independence [Weeks 5 to 12]
- Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale [Weeks 5 to 12]
Occurrence and severity of bleeding, measured using the WHO Bleeding Scale Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross blood loss; Grade 4=debilitating blood loss.
- Independent Reviewer-Assessed Best Response [up to week 12]
Participants were evaluated in accordance with the modified International Working Group (Cheson, 2006). CR: Bone marrow blasts <5%, Hgb ≥11g/dL, Hematologic Improvement - Platelets (Baseline <20Gi/L: >20 Gi/L and 2x baseline; Baseline ≥20 Gi/L: ≥50 Gi/L and 2x baseline), Neutrophils ≥1.0 Gi/L, Peripheral blasts 0%. PR: Bone marrow blasts decreased by ≥50% but >5%, Peripheral blood as in CR. Marrow CR: Bone marrow blasts <5% and decrease by ≥50%, Note any Hematologic Improvements, Stable disease: Failure to achieve PR, but no evidence of progression for >8w, Cytogenetic response: Complete: disappearance of chromosomal abnormality; no new abnormalities Partial: ≥50% reduction of chromosomal abnormality.
- Independent Reviewer Assessed Disease Progression [Up to week 12]
- Median Overall Survival [Up to 13 months]
- Summary of Health Outcomes [week 12]
The number of subject with medical resource utilization (MRU) data are reported in this table. MRU included number of emergency room visits, number of home healthcare visits, number of hospitalization days, number of medication or surgery specialist visits, number of procedures inpatient, number of procedures outpatient, number of non-study radiology visits, number of non-study laboratory visits, number of nurse practitioner/physician assistance/nurse visits, number of primary care physician visits, number of telephone consultations.
- Functional Assessment of Cancer Therapy (FACT) [Change from baseline, up to week 12]
The FACT-Th-18 is the most widely used and accepted tool evaluating health-related quality-of-life outcomes in cancer patients with chronically low platelets (where Th designates thrombocytopenia). The entire FACT-Th-18 was used in this trial, which includes the 18-item thrombocytopenia subscale used to assess the impact of symptoms, signs, and functional consequences of thrombocytopenia in MDS and AML subjects. The FACT-Th-18 is a validated and reliable instrument with known psychometric properties. FACT-ThS is an 18 item questionnaire specific to assessing the impact of symptoms, signs, and functional consequences of Thrombocytopenia. ThS score ranges from 0 to 72 with higher the score, the better the QoL. FACT G total score moves from 0 to 108 where higher the score, the better the HRQL. FACT-Th Total Score is calculated by adding the FACT-ThS and FACT-G score. Total score ranges from 0 to 180 and again, higher the score, the better the HRQL.
- EQ-5D Utility Score Analysis [Change from baseline, up to week 12]
EuroQoL Five Dimensions Questionnaire (EQ-5D) is a standardized generic preference based health related quality of life instrument. It records how one's health is "today" and consists of a descriptive system. The Descriptive system is Comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life. EQ-ED is a score.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 110 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts ≤50%) with thrombocytopenia due to bone marrow insufficiency from the disease or prior treatment. Subjects with transient thrombocytopenia due to active treatment with disease modifying agents or chemotherapy (except for hydroxyurea) are excluded.
-
Subjects must have Grade 4 thrombocytopenia (platelet counts <25 Gi/L) due to bone marrow insufficiency (or Grade 4 thrombocytopenia, but platelet count greater than or equal to 25 Gi/L due to platelet transfusion). In addition, subjects must have had at least one of the following during the 4 week screening period: platelet transfusion, or symptomatic bleeding or platelet count <10 Gi/L. Subjects whose thrombocytopenia below 10 Gi/L is due to causes other than bone marrow insufficiency (e.g., fever, infection, autoimmune disease) are not eligible.
-
Subjects must have platelet count, bleeding and platelet transfusion data available over a period of at least 4 weeks prior to randomization.
-
Prior systemic treatment for malignancy, with the exception of hydroxyurea, must have been discontinued prior to entry into the study: at least 4 weeks before Day 1 for the following: chemotherapy, demethylating agents (azacitidine or decitabine), lenalidomide, thalidomide, clofarabine and IL-11(oprelvekin); at least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin.
-
Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT.
-
Subjects must be stable and, in the opinion of the investigator, be expected to complete a 12 week treatment period.
-
ECOG Status 0-2.
-
Subject must be able to understand and comply with protocol requirements and instructions.
-
Subject has signed and dated an informed consent form.
-
Adequate baseline organ function defined by the criteria below: total bilirubin ≤ 1.5xULN except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect (hemolytic) bilirubin in the absence of ALT abnormality), ALT ≤ 3xULN, creatinine ≤ 2.5xULN
-
Women must be either of non-child bearing potential or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the first dose of study treatment.
-
In France, a subject eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Exclusion Criteria:
-
Subjects with MDS and an IPSS of low or intermediate-1 risk at screening.
-
Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML secondary to a myeloproliferative neoplasm.
-
History of treatment with romiplostim or other TPO-R agonists.
-
Subjects with a QTc >480 msec (QTc >510 msec for subjects with Bundle Branch Block).
-
Leukocytosis ≥25,000/uL on Day 1 of treatment with study medication.
-
Subjects with known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
-
Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day 1.
-
Current alcohol or drug abuse.
-
Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
-
Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).
-
Subjects infected with Human Immunodeficiency Virus (HIV).
-
Subjects with liver cirrhosis (as determined by the investigator).
-
Subjects receiving or planned to receive any prohibited medication.
-
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidone, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjects' participation.
-
In France, subjects who have participated in any study using an investigational drug during the previous 30 days.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Phoenix | Arizona | United States | 85016 |
| 2 | Novartis Investigative Site | Hot Springs | Arkansas | United States | 71913 |
| 3 | Novartis Investigative Site | Jonesboro | Arkansas | United States | 72401 |
| 4 | Novartis Investigative Site | Los Angeles | California | United States | 90095 |
| 5 | Novartis Investigative Site | Stanford | California | United States | 94305 |
| 6 | Novartis Investigative Site | Jacksonville | Florida | United States | 32256 |
| 7 | Novartis Investigative Site | Orlando | Florida | United States | 32806 |
| 8 | Novartis Investigative Site | West Palm Beach | Florida | United States | 33401 |
| 9 | Novartis Investigative Site | Augusta | Georgia | United States | 30912 |
| 10 | Novartis Investigative Site | Baltimore | Maryland | United States | 21201 |
| 11 | Novartis Investigative Site | Boston | Massachusetts | United States | 02115 |
| 12 | Novartis Investigative Site | Kansas City | Missouri | United States | 64128 |
| 13 | Novartis Investigative Site | Hackensack | New Jersey | United States | 07601 |
| 14 | Novartis Investigative Site | Voorhees | New Jersey | United States | 08043 |
| 15 | Novartis Investigative Site | The Bronx | New York | United States | 10467 |
| 16 | Novartis Investigative Site | Philadelphia | Pennsylvania | United States | 19140 |
| 17 | Novartis Investigative Site | Seattle | Washington | United States | 98108 |
| 18 | Novartis Investigative Site | Milwaukee | Wisconsin | United States | 53226 |
| 19 | Novartis Investigative Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1431FWO |
| 20 | Novartis Investigative Site | La Plata | Buenos Aires | Argentina | B1900AXI |
| 21 | Novartis Investigative Site | Ciudad Autonoma de Buenos Aires | Argentina | C1025ABH | |
| 22 | Novartis Investigative Site | Ciudad Autónoma de Buenos Aires | Argentina | 1405 | |
| 23 | Novartis Investigative Site | Ciudad Autónoma de Buenos Aires | Argentina | 1405 | |
| 24 | Novartis Investigative Site | Antwerpen | Belgium | 2060 | |
| 25 | Novartis Investigative Site | Brasschaat | Belgium | 2930 | |
| 26 | Novartis Investigative Site | Brugge | Belgium | 8000 | |
| 27 | Novartis Investigative Site | Bruxelles | Belgium | 1000 | |
| 28 | Novartis Investigative Site | Gent | Belgium | 9000 | |
| 29 | Novartis Investigative Site | Leuven | Belgium | 3000 | |
| 30 | Novartis Investigative Site | Yvoir | Belgium | 5530 | |
| 31 | Novartis Investigative Site | Goiânia - GO | Goiás | Brazil | 74605-020 |
| 32 | Novartis Investigative Site | Goiânia - GO | Goiás | Brazil | 74605-020 |
| 33 | Novartis Investigative Site | Curitiba | Paraná | Brazil | 81520-060 |
| 34 | Novartis Investigative Site | Curitiba | Paraná | Brazil | 81520-060 |
| 35 | Novartis Investigative Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 36 | Novartis Investigative Site | Barretos | São Paulo | Brazil | 14784-400 |
| 37 | Novartis Investigative Site | Barretos | São Paulo | Brazil | 14784-400 |
| 38 | Novartis Investigative Site | Rio de Janeiro | Brazil | 20211-030 | |
| 39 | Novartis Investigative Site | São Paulo | Brazil | 01236030 | |
| 40 | Novartis Investigative Site | São Paulo | Brazil | 01236030 | |
| 41 | Novartis Investigative Site | Halifax | Nova Scotia | Canada | B3H 2Y9 |
| 42 | Novartis Investigative Site | Toronto | Ontario | Canada | M5G 2M9 |
| 43 | Novartis Investigative Site | Montreal | Quebec | Canada | H3T 1E2 |
| 44 | Novartis Investigative Site | Brno | Czechia | 625 00 | |
| 45 | Novartis Investigative Site | Praha 10 | Czechia | 100 34 | |
| 46 | Novartis Investigative Site | Praha 2 | Czechia | 128 08 | |
| 47 | Novartis Investigative Site | Praha | Czechia | 128 20 | |
| 48 | Novartis Investigative Site | Mannheim | Baden-Wuerttemberg | Germany | 68167 |
| 49 | Novartis Investigative Site | Stuttgart | Baden-Wuerttemberg | Germany | 70199 |
| 50 | Novartis Investigative Site | Goettingen | Niedersachsen | Germany | 37075 |
| 51 | Novartis Investigative Site | Duesseldorf | Nordrhein-Westfalen | Germany | 40225 |
| 52 | Novartis Investigative Site | Koeln | Nordrhein-Westfalen | Germany | 50937 |
| 53 | Novartis Investigative Site | Dresden | Sachsen | Germany | 01307 |
| 54 | Novartis Investigative Site | Athens | Greece | 11527 | |
| 55 | Novartis Investigative Site | Heraklion, Crete | Greece | 71201 | |
| 56 | Novartis Investigative Site | Ioannina | Greece | 45 500 | |
| 57 | Novartis Investigative Site | Thessaloniki | Greece | 57010 | |
| 58 | Novartis Investigative Site | Chai Wan | Hong Kong | ||
| 59 | Novartis Investigative Site | Shatin, New Territories | Hong Kong | ||
| 60 | Novartis Investigative Site | Budapest | Hungary | 1088 | |
| 61 | Novartis Investigative Site | Debrecen | Hungary | 4012 | |
| 62 | Novartis Investigative Site | Kaposvár | Hungary | 7400 | |
| 63 | Novartis Investigative Site | Kaposvár | Hungary | 7400 | |
| 64 | Novartis Investigative Site | Szeged | Hungary | 6720 | |
| 65 | Novartis Investigative Site | Cork | Ireland | ||
| 66 | Novartis Investigative Site | Dublin | Ireland | 7 | |
| 67 | Novartis Investigative Site | James Street | Ireland | 8 | |
| 68 | Novartis Investigative Site | Limerick | Ireland | ||
| 69 | Novartis Investigative Site | Tallaght, Dublin | Ireland | 24 | |
| 70 | Novartis Investigative Site | Tullamore | Ireland | ||
| 71 | Novartis Investigative Site | Beer-Sheva | Israel | 84101 | |
| 72 | Novartis Investigative Site | Haifa | Israel | 31048 | |
| 73 | Novartis Investigative Site | Haifa | Israel | 31096 | |
| 74 | Novartis Investigative Site | Holon | Israel | 58100 | |
| 75 | Novartis Investigative Site | Jerusalem | Israel | 91120 | |
| 76 | Novartis Investigative Site | Petach-Tikva | Israel | 49100 | |
| 77 | Novartis Investigative Site | Ramat Gan | Israel | 52621 | |
| 78 | Novartis Investigative Site | Rehovot | Israel | 76100 | |
| 79 | Novartis Investigative Site | Tel Aviv | Israel | 64239 | |
| 80 | Novartis Investigative Site | Bologna | Emilia-Romagna | Italy | 40138 |
| 81 | Novartis Investigative Site | Brescia | Lombardia | Italy | 25123 |
| 82 | Novartis Investigative Site | Milano | Lombardia | Italy | 20122 |
| 83 | Novartis Investigative Site | Milano | Lombardia | Italy | 20162 |
| 84 | Novartis Investigative Site | Alessandria | Piemonte | Italy | 15100 |
| 85 | Novartis Investigative Site | Firenze | Toscana | Italy | 50134 |
| 86 | Novartis Investigative Site | Hwasun | Korea, Republic of | 519-809 | |
| 87 | Novartis Investigative Site | Seoul | Korea, Republic of | 110-744 | |
| 88 | Novartis Investigative Site | Seoul | Korea, Republic of | 120-752 | |
| 89 | Novartis Investigative Site | Monterrey | Nuevo León | Mexico | 64460 |
| 90 | Novartis Investigative Site | Monterrey | Nuevo León | Mexico | 64460 |
| 91 | Novartis Investigative Site | Chihuahua | Mexico | 31203 | |
| 92 | Novartis Investigative Site | Mexico City | Mexico | CP 14080 | |
| 93 | Novartis Investigative Site | Oaxaca | Mexico | 68000 | |
| 94 | Novartis Investigative Site | Amsterdam | Netherlands | 1081 HV | |
| 95 | Novartis Investigative Site | Chorzow | Poland | 41-500 | |
| 96 | Novartis Investigative Site | Torun | Poland | 87-100 | |
| 97 | Novartis Investigative Site | Warszawa | Poland | 02-097 | |
| 98 | Novartis Investigative Site | San Juan | Puerto Rico | 00927 | |
| 99 | Novartis Investigative Site | Nizhniy Novgorod | Russian Federation | 603126 | |
| 100 | Novartis Investigative Site | Petrozavodsk | Russian Federation | 185019 | |
| 101 | Novartis Investigative Site | St'Petersburg | Russian Federation | 191024 | |
| 102 | Novartis Investigative Site | St'Petersburg | Russian Federation | 197341 | |
| 103 | Novartis Investigative Site | St. Petersburg | Russian Federation | 197 089 | |
| 104 | Novartis Investigative Site | Barcelona | Spain | 08036 | |
| 105 | Novartis Investigative Site | Granada | Spain | ||
| 106 | Novartis Investigative Site | Madrid | Spain | 28034 | |
| 107 | Novartis Investigative Site | Málaga | Spain | 29010 | |
| 108 | Novartis Investigative Site | Málaga | Spain | 29010 | |
| 109 | Novartis Investigative Site | Pozuelo de Alarcón/Madrid | Spain | 28223 | |
| 110 | Novartis Investigative Site | Pozuelo de Alarcón/Madrid | Spain | 28223 | |
| 111 | Novartis Investigative Site | Salamanca | Spain | 37007 | |
| 112 | Novartis Investigative Site | Santander | Spain | 39008 | |
| 113 | Novartis Investigative Site | Kaohsiung City | Taiwan | 83301 | |
| 114 | Novartis Investigative Site | Tainan County | Taiwan | 736 | |
| 115 | Novartis Investigative Site | Taoyuan County | Taiwan | 333 | |
| 116 | Novartis Investigative Site | Bangkok | Thailand | 10330 | |
| 117 | Novartis Investigative Site | Bangkok | Thailand | 10400 | |
| 118 | Novartis Investigative Site | Bangkok | Thailand | 10700 | |
| 119 | Novartis Investigative Site | Khon Kaen | Thailand | 40002 | |
| 120 | Novartis Investigative Site | Songkla | Thailand | 90110 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01440374
Other Study ID Numbers:
- 114968
- 2011-000114-19
First Posted:
Sep 26, 2011
Last Update Posted:
Jun 5, 2017
Last Verified:
May 1, 2017
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Part 1, 17 subjects received open-label eltrombopag. Part 2, 145 subjects were randomized to receive eltrombopag plus SOC (N=98) or placebo plus SOC (N=47). Part 3, 59 subjects from Part 2 entered Part 3. SOC was allowed as needed throughout the study. Subjects could receive disease-modifying therapy as needed. |
|---|---|
| Pre-assignment Detail | Participants with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and Grade 4 thrombocytopenia due to bone marrow insufficiency and had at least one of the following: platelet count <10 Giga cells per liter, platelet transfusion or symptomatic hemorrhagic event during the 4 weeks prior to enrollment, were enrolled in the study. |
| Arm/Group Title | Part 1: Eltrombopag | Part 2: Placebo | Part 2: Eltrombopag | Part 3: Eltrombopag |
|---|---|---|---|---|
| Arm/Group Description | The eltrombopag starting dose the participants received was 100 milligrams (mg) daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | 23 subjects of the 47 randomized to the placebo group in Part 2 entered part 3. 36 subjects of the 98 randomized to the Etrombopag group in Part 2 entered part 3. All subjects received eltrombopag. Part 3 subjects could also have received treatment for their disease per local SOC, including azacitidine, decitabine, lenalidomide, and chemotherapy. The duration of Part 3 was to be 10 months for subjects from Part 1and 9 months for subjects from Part 2. |
| Period Title: Part 1: Open-label Phase | ||||
| STARTED | 17 | 0 | 0 | 0 |
| COMPLETED | 11 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 0 | 0 | 0 |
| Period Title: Part 1: Open-label Phase | ||||
| STARTED | 0 | 47 | 98 | 0 |
| COMPLETED | 0 | 27 | 43 | 0 |
| NOT COMPLETED | 0 | 20 | 55 | 0 |
| Period Title: Part 1: Open-label Phase | ||||
| STARTED | 0 | 0 | 0 | 59 |
| COMPLETED | 0 | 0 | 0 | 27 |
| NOT COMPLETED | 0 | 0 | 0 | 32 |
Baseline Characteristics
| Arm/Group Title | Part 1: Eltrombopag | Part 2: Placebo | Part 2: Eltrombopag | Total |
|---|---|---|---|---|
| Arm/Group Description | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Total of all reporting groups |
| Overall Participants | 17 | 47 | 98 | 162 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
71.5
(10.78)
|
70.6
(10.72)
|
72.3
(8.94)
|
71.8
(9.56)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
7
41.2%
|
16
34%
|
32
32.7%
|
55
34%
|
| Male |
10
58.8%
|
31
66%
|
66
67.3%
|
107
66%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||
| African American/African Heritage |
0
0%
|
0
0%
|
1
1%
|
1
0.6%
|
| Asian - East Asian Heritage |
3
17.6%
|
5
10.6%
|
9
9.2%
|
17
10.5%
|
| Asian - South East Asian Heritage |
0
0%
|
2
4.3%
|
2
2%
|
4
2.5%
|
| White - Arabic/North African Heritage |
0
0%
|
1
2.1%
|
5
5.1%
|
6
3.7%
|
| White - White/Caucasian/European Heritage |
14
82.4%
|
39
83%
|
81
82.7%
|
134
82.7%
|
Outcome Measures
| Title | Number of Participants With Platelet Response up to Week 8 During Part 1 |
|---|---|
| Description | A participant was considered as a responder if he/she met the following response criteria: a Baseline platelet count <20 Giga cells per liter (Gi/L) and a post-Baseline increased to >20 Gi/L and at least 2 times the Baseline value; or a Baseline platelet count >=20 Gi/L and a post-Baseline absolute platelet count increased to >=50 Gi/L and at least 2 times the Baseline value. The response criteria was evaluated at each visit. Increase in platelet count observed up to 3 days after a platelet transfusion was not considered as a platelet response. The Part 1 Population was comprised of all participants enrolled into Part 1. |
| Time Frame | From Baseline up to Week 8 during Part 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 1 Population: all subjects who enrolled in Part 1. |
| Arm/Group Title | Part 1: Eltrombopag |
|---|---|
| Arm/Group Description | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks. |
| Measure Participants | 17 |
| Number [Participants] |
4
23.5%
|
| Title | Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2 |
|---|---|
| Description | A participant was considered to have a CRTE at a given assessment if he/she had platelet counts <10 Gi/L, or platelet transfusions, or >=Grade 3 hemorrhagic adverse events. CRTEs during Weeks 5 to 12 were compared between treatments using a generalized linear mixed model. Average of weekly proportion of subjects with CRTE during Week 5 to 12 was estimated for each treatment. Intent to Treat (ITT) Population was comprised of all randomized participants during Part 2. |
| Time Frame | From Week 5 up to Week 12 during Part 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-To-Treat (ITT) Population: all randomized subjects in part 2) |
| Arm/Group Title | Part 2: Placebo | Part 2: Eltrombopag |
|---|---|---|
| Arm/Group Description | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 47 | 98 |
| Mean (95% Confidence Interval) [percentages of participants] |
69
405.9%
|
54
114.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: Eltrombopag, Part 2: Eltrombopag |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0315 |
| Comments | ||
| Method | Generalized Linear Mixed Models | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.202 | |
| Confidence Interval |
(2-Sided) 95% 0.047 to 0.868 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) |
|---|---|
| Description | |
| Time Frame | Day 1 to week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population: all subjects in All Subjects Population who had a PK blood sample obtained/analyzed. |
| Arm/Group Title | Part 1: Eltrombopag |
|---|---|
| Arm/Group Description | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks. |
| Measure Participants | 17 |
| Baseline/day 1 (Pre-dose PK) |
0
(0)
|
| Day8 week 1 (Pre-dose PK) |
7.7
(3.96)
|
| Day15 week 2 (Pre-dose PK) |
7.2
(5.17)
|
| Day22 week 3 (Pre-dose PK) |
14.3
(10.63)
|
| Day29 week 3 (2-6hrs post-dose PK) |
20.8
(14.98)
|
| Day36 week 5 (Pre-dose PK) |
20.2
(16.37)
|
| Day43 week6 (2-6hrs post-dose PK) |
41.2
(32.56)
|
| Day50 week 7 (Pre-dose PK) |
30.4
(27.95)
|
| Day57 week 8 (2-6hrs post-dose PK) |
30.1
(18.99)
|
| Title | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) |
|---|---|
| Description | |
| Time Frame | Day 1 to week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population |
| Arm/Group Title | Part 2: Eltrombopag |
|---|---|
| Arm/Group Description | The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks. |
| Measure Participants | 97 |
| Baseline/day 1 (Pre-dose PK) |
0
(0)
|
| Day15 week 2 (Pre-dose PK) |
10.1
(5.54)
|
| Day22 week 3 (2-6hrs post-dose PK) |
24.0
(14.6)
|
| Day29 week 4 (Pre-dose PK) |
20.2
(13.61)
|
| Day43 week 6 (Pre-dose PK) |
29.0
(18.13)
|
| Day50 week 7 (2-6hrs post-dose PK) |
42.9
(22.37)
|
| Day57 week8 (Pre-dose PK) |
36.3
(20.91)
|
| Day71 week 10 (Pre-dose PK) |
33.5
(20.40)
|
| Day78 week 11 (2-6hrs post-dose PK) |
41.2
(24.91)
|
| Day85 week12 (Pre-dose PK) |
30.7
(18.03)
|
| Title | Mean Number of Platelet Transfusions |
|---|---|
| Description | |
| Time Frame | Weeks 5 to 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Mean (Standard Deviation) [Number of platelet transfusions] |
18.8
(18.60)
|
15.7
(20.36)
|
| Title | Hematologic Improvement |
|---|---|
| Description | Definitions of hematologic improvement for platelets, neutrophils, and hemoglobin were based on modified International Working Group (IWG) consensus criteria. |
| Time Frame | Weeks 5 to 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Any Improvement |
10
|
4
|
| Platelets |
8
|
2
|
| Neutrophils |
4
|
4
|
| Hemoglobin |
0
|
0
|
| Platelets and neutrophils |
2
|
2
|
| Platelets and hemoglobin |
0
|
0
|
| Platelets, hemoglobin and neutrophils |
0
|
0
|
| Neutrophils and hemoglobin |
0
|
0
|
| Title | Change in Mean Platelet Count |
|---|---|
| Description | |
| Time Frame | Baseline to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Day8 week1 |
3.36
(11.795)
|
1.66
(6.249)
|
| Day15 week2 |
10.41
(60.225)
|
3.06
(9.675)
|
| Day22 week3 |
6.23
(22.872)
|
2.13
(9.258)
|
| Day29 week4 |
5.63
(17.582)
|
2.44
(11.215)
|
| Day36 week5 |
8.58
(22.504)
|
5.9
(16.000)
|
| Day43 week6 |
8.64
(19.779)
|
5.93
(21.960)
|
| Day50 week7 |
9.91
(25.561)
|
6.74
(31.074)
|
| Day57 week8 |
9.67
(23.243)
|
7.84
(34.213)
|
| Day64 week9 |
12.84
(27.272)
|
6.75
(31.709)
|
| Day71 week10 |
15.97
(33.866)
|
6.23
(30.941)
|
| Day78 week11 |
14.42
(36.901)
|
6.92
(26.906)
|
| Day 85 week12 |
9.06
(28.259)
|
4.85
(26.219)
|
| Title | Maximum Duration of Platelet Transfusion Independence |
|---|---|
| Description | |
| Time Frame | Weeks 5 to 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Mean (Standard Deviation) [maximum duration of platelet transfusion] |
26.3
(21.47)
|
25.4
(19.70)
|
| Title | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale |
|---|---|
| Description | Occurrence and severity of bleeding, measured using the WHO Bleeding Scale Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross blood loss; Grade 4=debilitating blood loss. |
| Time Frame | Weeks 5 to 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Grade 0 (no bleeding) |
15
|
4
|
| Grade 1 (petechiae) |
31
|
22
|
| Grade 2 (mild blood loss) |
41
|
14
|
| Grade 3 (gross blood loss) |
5
|
3
|
| Grade 4 (debilitating blood loss) |
1
|
3
|
| Grades 0 - 1 |
46
|
26
|
| Grades 1 - 4 |
78
|
42
|
| Grades 2 - 4 |
47
|
20
|
| Title | Independent Reviewer-Assessed Best Response |
|---|---|
| Description | Participants were evaluated in accordance with the modified International Working Group (Cheson, 2006). CR: Bone marrow blasts <5%, Hgb ≥11g/dL, Hematologic Improvement - Platelets (Baseline <20Gi/L: >20 Gi/L and 2x baseline; Baseline ≥20 Gi/L: ≥50 Gi/L and 2x baseline), Neutrophils ≥1.0 Gi/L, Peripheral blasts 0%. PR: Bone marrow blasts decreased by ≥50% but >5%, Peripheral blood as in CR. Marrow CR: Bone marrow blasts <5% and decrease by ≥50%, Note any Hematologic Improvements, Stable disease: Failure to achieve PR, but no evidence of progression for >8w, Cytogenetic response: Complete: disappearance of chromosomal abnormality; no new abnormalities Partial: ≥50% reduction of chromosomal abnormality. |
| Time Frame | up to week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Responder |
1
|
1
|
| Complete response (CR) |
0
|
0
|
| Morphologic CR |
0
|
1
|
| Morphologic leukemia-free state |
0
|
0
|
| Marrow CR |
1
|
0
|
| Cytogenetic CR |
0
|
0
|
| Molecular CR |
0
|
0
|
| Non-responder |
97
|
46
|
| Partial response |
0
|
0
|
| Stable disease (non-responder) |
18
|
10
|
| Progressive disease (non-responder) |
41
|
28
|
| Not evaluable (non-responder) |
36
|
8
|
| Missing (non-responder) |
2
|
0
|
| Title | Independent Reviewer Assessed Disease Progression |
|---|---|
| Description | |
| Time Frame | Up to week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Disease progression |
61
(21.47)
|
36
(19.70)
|
| No disease progression |
12
|
6
|
| Not evaluable |
23
|
5
|
| Missing |
2
|
0
|
| Title | Median Overall Survival |
|---|---|
| Description | |
| Time Frame | Up to 13 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Median (95% Confidence Interval) [Months] |
4.27
|
4.6
|
| Title | Summary of Health Outcomes |
|---|---|
| Description | The number of subject with medical resource utilization (MRU) data are reported in this table. MRU included number of emergency room visits, number of home healthcare visits, number of hospitalization days, number of medication or surgery specialist visits, number of procedures inpatient, number of procedures outpatient, number of non-study radiology visits, number of non-study laboratory visits, number of nurse practitioner/physician assistance/nurse visits, number of primary care physician visits, number of telephone consultations. |
| Time Frame | week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Number of emergency room visits (n=17, n=10) |
1
|
0
|
| Number of home healthcare visits (n=17, n=10) |
2
|
1
|
| Number of hospitalization days (n=17, n=10) |
5
|
4
|
| Number of med/surg specialist visits (n=17, n=10) |
1
|
3
|
| Number of procedures inpatient (n=17, n=10) |
2
|
1
|
| Number of procedures outpatient (n=17, n=10) |
1
|
1
|
| Number of non-study radiology visits (n=2, n=2) |
2
|
2
|
| Number of nurse prac/pa/nurse visits (n=17, n=10) |
5
|
3
|
| Number of primary care physician visits (n=17,10) |
7
|
1
|
| Number of telephone consultations (n=17, n=10) |
1
|
0
|
| Number of non-study laboratory visits (n=17, n=10) |
8
|
6
|
| Title | Functional Assessment of Cancer Therapy (FACT) |
|---|---|
| Description | The FACT-Th-18 is the most widely used and accepted tool evaluating health-related quality-of-life outcomes in cancer patients with chronically low platelets (where Th designates thrombocytopenia). The entire FACT-Th-18 was used in this trial, which includes the 18-item thrombocytopenia subscale used to assess the impact of symptoms, signs, and functional consequences of thrombocytopenia in MDS and AML subjects. The FACT-Th-18 is a validated and reliable instrument with known psychometric properties. FACT-ThS is an 18 item questionnaire specific to assessing the impact of symptoms, signs, and functional consequences of Thrombocytopenia. ThS score ranges from 0 to 72 with higher the score, the better the QoL. FACT G total score moves from 0 to 108 where higher the score, the better the HRQL. FACT-Th Total Score is calculated by adding the FACT-ThS and FACT-G score. Total score ranges from 0 to 180 and again, higher the score, the better the HRQL. |
| Time Frame | Change from baseline, up to week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| FACTG week 5 (n=61. n=34) |
-0.79
(1.64)
|
-3.15
(2.19)
|
| FACTG week 9 (n=46. n=28) |
-4.83
(1.82)
|
-2.76
(2.34)
|
| FACTG week12 (n=37. n=26) |
-3.38
(1.94)
|
-4.17
(2.39)
|
| FACTHTOI week 5 (n=61, n=34) |
0.91
(2.04)
|
-2.28
(2.74)
|
| FACTHTOI week 9 (n=46, n=28) |
-1.69
(2.24)
|
0.19
(2.89)
|
| FACTHTOI week 12 (n=37, n=26) |
-0.26
(2.37)
|
-1.56
(2.95)
|
| Title | EQ-5D Utility Score Analysis |
|---|---|
| Description | EuroQoL Five Dimensions Questionnaire (EQ-5D) is a standardized generic preference based health related quality of life instrument. It records how one's health is "today" and consists of a descriptive system. The Descriptive system is Comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life. EQ-ED is a score. |
| Time Frame | Change from baseline, up to week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Part 2 Population (Intent-to-Treat population) |
| Arm/Group Title | Part 2: Eltrombopag | Part 2: Placebo |
|---|---|---|
| Arm/Group Description | Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. |
| Measure Participants | 98 | 47 |
| Week 5 (n=55. n=34) |
-0.01
(0.04)
|
-0.15
(0.05)
|
| Week 9 (n=43. n=27) |
-0.08
(0.04)
|
-0.06
(0.05)
|
| Week 12 (n=36. n=26) |
-0.09
(0.05)
|
-0.11
(0.05)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Eltrombopag, Part 1 Subjects | Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects | Placebo, Part 2 Plus 1 Day From Part 2 Subjects | Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects | ||||
| Arm/Group Description | Eltrombopag, Part 1 subjects | Eltrombopag, Part 2 plus 1 day from Part 2 subjects | Placebo, Part 2 plus 1 day from Part 2 subjects | Eltrombopag, Part 3 plus 30 Days from Part 2 subjects | ||||
All Cause Mortality |
||||||||
| Eltrombopag, Part 1 Subjects | Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects | Placebo, Part 2 Plus 1 Day From Part 2 Subjects | Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Eltrombopag, Part 1 Subjects | Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects | Placebo, Part 2 Plus 1 Day From Part 2 Subjects | Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/17 (52.9%) | 56/97 (57.7%) | 32/47 (68.1%) | 39/59 (66.1%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/17 (0%) | 2/97 (2.1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Febrile neutropenia | 0/17 (0%) | 7/97 (7.2%) | 7/47 (14.9%) | 6/59 (10.2%) | ||||
| Haemolytic anaemia | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Leukocytosis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 3/59 (5.1%) | ||||
| Lymphadenopathy | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Splenic artery thrombosis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Splenic infarction | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Splenomegaly | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Thrombocytopenia | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Cardiac failure | 0/17 (0%) | 1/97 (1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Myocardial infarction | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Palpitations | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Endocrine disorders | ||||||||
| Adrenal disorder | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Eye disorders | ||||||||
| Retinal vein occlusion | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Vitreous haemorrhage | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/17 (5.9%) | 2/97 (2.1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Constipation | 0/17 (0%) | 2/97 (2.1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Diarrhoea | 0/17 (0%) | 1/97 (1%) | 3/47 (6.4%) | 1/59 (1.7%) | ||||
| Gastric haemorrhage | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Gastrointestinal haemorrhage | 0/17 (0%) | 2/97 (2.1%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Gastrointestinal hypomotility | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Intestinal haemorrhage | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Intestinal ischaemia | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Melaena | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Oral mucosal blistering | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Retroperitoneal haemorrhage | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Upper gastrointestinal haemorrhage | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 2/59 (3.4%) | ||||
| Vomiting | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| General disorders | ||||||||
| Asthenia | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 2/59 (3.4%) | ||||
| Chest discomfort | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Chills | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Death | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Disease progression | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Fatigue | 0/17 (0%) | 1/97 (1%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| General physical health deterioration | 0/17 (0%) | 2/97 (2.1%) | 2/47 (4.3%) | 2/59 (3.4%) | ||||
| Malaise | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Multi-organ failure | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Non-cardiac chest pain | 0/17 (0%) | 0/97 (0%) | 2/47 (4.3%) | 0/59 (0%) | ||||
| Pyrexia | 2/17 (11.8%) | 7/97 (7.2%) | 6/47 (12.8%) | 7/59 (11.9%) | ||||
| Sudden death | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Hepatobiliary disorders | ||||||||
| Bile duct stone | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cholangitis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Hepatitis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Infections and infestations | ||||||||
| Abscess neck | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Appendicitis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Bronchitis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 4/59 (6.8%) | ||||
| Catheter site cellulitis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cellulitis | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cholecystitis infective | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Clostridium difficile colitis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Cystitis | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Device related infection | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Endocarditis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Enteritis infectious | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Escherichia bacteraemia | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Escherichia sepsis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Gastroenteritis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Herpes zoster | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Infection | 0/17 (0%) | 2/97 (2.1%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Influenza | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Lower respiratory tract infection | 0/17 (0%) | 2/97 (2.1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Lung infection | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Osteomyelitis | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Otitis externa | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Pneumonia | 1/17 (5.9%) | 14/97 (14.4%) | 5/47 (10.6%) | 10/59 (16.9%) | ||||
| Respiratory tract infection | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Sepsis | 4/17 (23.5%) | 8/97 (8.2%) | 5/47 (10.6%) | 6/59 (10.2%) | ||||
| Septic shock | 2/17 (11.8%) | 1/97 (1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Splenic abscess | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Staphylococcal infection | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Staphylococcal sepsis | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Streptococcal sepsis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Tooth infection | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Upper respiratory tract infection | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Urinary tract infection | 0/17 (0%) | 3/97 (3.1%) | 1/47 (2.1%) | 5/59 (8.5%) | ||||
| Urosepsis | 0/17 (0%) | 1/97 (1%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Viral oesophagitis | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Head injury | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Subdural haematoma | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Subdural haemorrhage | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Transfusion reaction | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Wound haemorrhage | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Aspartate aminotransferase increased | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Blood bilirubin increased | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Haemoglobin decreased | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| International normalised ratio increased | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| White blood cell count increased | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Hypokalaemia | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Bone pain | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Muscular weakness | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 2/59 (3.4%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acute myeloid leukaemia | 0/17 (0%) | 2/97 (2.1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Lung neoplasm | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Myelodysplastic syndrome | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Nervous system disorders | ||||||||
| Cerebral haemorrhage | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Diabetic neuropathy | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Generalised tonic-clonic seizure | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Haemorrhage intracranial | 0/17 (0%) | 1/97 (1%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Seizure | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Subarachnoid haemorrhage | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Syncope | 0/17 (0%) | 2/97 (2.1%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Haematuria | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Renal failure | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory failure | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cough | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Dyspnoea | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Laryngeal oedema | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Lung consolidation | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Lung disorder | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Pneumonitis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Pulmonary alveolar haemorrhage | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Pulmonary embolism | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Pulmonary oedema | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Respiratory distress | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Respiratory failure | 1/17 (5.9%) | 2/97 (2.1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Vascular disorders | ||||||||
| Arterial thrombosis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Haematoma | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Hypotension | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Thrombophlebitis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Eltrombopag, Part 1 Subjects | Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects | Placebo, Part 2 Plus 1 Day From Part 2 Subjects | Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/17 (100%) | 89/97 (91.8%) | 44/47 (93.6%) | 54/59 (91.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 3/17 (17.6%) | 8/97 (8.2%) | 2/47 (4.3%) | 2/59 (3.4%) | ||||
| Blood disorder | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Disseminated intravascular coagulation | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Febrile neutropenia | 1/17 (5.9%) | 4/97 (4.1%) | 0/47 (0%) | 2/59 (3.4%) | ||||
| Haemolysis | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Leukocytosis | 0/17 (0%) | 3/97 (3.1%) | 1/47 (2.1%) | 4/59 (6.8%) | ||||
| Neutropenia | 1/17 (5.9%) | 2/97 (2.1%) | 2/47 (4.3%) | 3/59 (5.1%) | ||||
| Cardiac disorders | ||||||||
| Pericardial effusion | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Hypoacusis | 1/17 (5.9%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Vertigo | 1/17 (5.9%) | 1/97 (1%) | 2/47 (4.3%) | 2/59 (3.4%) | ||||
| Eye disorders | ||||||||
| Conjunctival haemorrhage | 1/17 (5.9%) | 2/97 (2.1%) | 4/47 (8.5%) | 0/59 (0%) | ||||
| Eye haemorrhage | 0/17 (0%) | 5/97 (5.2%) | 0/47 (0%) | 0/59 (0%) | ||||
| Ocular hyperaemia | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Ocular icterus | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 5/59 (8.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/17 (5.9%) | 6/97 (6.2%) | 3/47 (6.4%) | 5/59 (8.5%) | ||||
| Abdominal pain upper | 0/17 (0%) | 6/97 (6.2%) | 2/47 (4.3%) | 2/59 (3.4%) | ||||
| Colitis | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Constipation | 3/17 (17.6%) | 12/97 (12.4%) | 0/47 (0%) | 7/59 (11.9%) | ||||
| Diarrhoea | 4/17 (23.5%) | 20/97 (20.6%) | 5/47 (10.6%) | 11/59 (18.6%) | ||||
| Gingival bleeding | 1/17 (5.9%) | 13/97 (13.4%) | 8/47 (17%) | 7/59 (11.9%) | ||||
| Gingival swelling | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Mouth haemorrhage | 0/17 (0%) | 9/97 (9.3%) | 7/47 (14.9%) | 7/59 (11.9%) | ||||
| Nausea | 1/17 (5.9%) | 13/97 (13.4%) | 8/47 (17%) | 14/59 (23.7%) | ||||
| Vomiting | 2/17 (11.8%) | 6/97 (6.2%) | 5/47 (10.6%) | 6/59 (10.2%) | ||||
| General disorders | ||||||||
| Asthenia | 3/17 (17.6%) | 4/97 (4.1%) | 5/47 (10.6%) | 6/59 (10.2%) | ||||
| Catheter site related reaction | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Fatigue | 1/17 (5.9%) | 23/97 (23.7%) | 3/47 (6.4%) | 9/59 (15.3%) | ||||
| Oedema peripheral | 0/17 (0%) | 9/97 (9.3%) | 3/47 (6.4%) | 7/59 (11.9%) | ||||
| Pain | 1/17 (5.9%) | 2/97 (2.1%) | 1/47 (2.1%) | 2/59 (3.4%) | ||||
| Pyrexia | 4/17 (23.5%) | 18/97 (18.6%) | 10/47 (21.3%) | 12/59 (20.3%) | ||||
| Xerosis | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatotoxicity | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Hyperbilirubinaemia | 1/17 (5.9%) | 3/97 (3.1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Immune system disorders | ||||||||
| Drug hypersensitivity | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Infections and infestations | ||||||||
| Acute sinusitis | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Arthritis infective | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Bacterial infection | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Bronchopulmonary aspergillosis | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cellulitis | 0/17 (0%) | 2/97 (2.1%) | 3/47 (6.4%) | 2/59 (3.4%) | ||||
| Escherichia infection | 1/17 (5.9%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Klebsiella sepsis | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Nasopharyngitis | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 7/59 (11.9%) | ||||
| Otitis externa | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Pneumonia | 4/17 (23.5%) | 3/97 (3.1%) | 1/47 (2.1%) | 2/59 (3.4%) | ||||
| Skin infection | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Upper respiratory tract infection | 3/17 (17.6%) | 2/97 (2.1%) | 2/47 (4.3%) | 0/59 (0%) | ||||
| Urinary tract infection | 1/17 (5.9%) | 5/97 (5.2%) | 2/47 (4.3%) | 3/59 (5.1%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/17 (5.9%) | 4/97 (4.1%) | 3/47 (6.4%) | 5/59 (8.5%) | ||||
| Fall | 1/17 (5.9%) | 1/97 (1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Laceration | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Post procedural haematoma | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Transfusion reaction | 0/17 (0%) | 2/97 (2.1%) | 3/47 (6.4%) | 1/59 (1.7%) | ||||
| Wound | 0/17 (0%) | 0/97 (0%) | 0/47 (0%) | 3/59 (5.1%) | ||||
| Investigations | ||||||||
| Activated partial thromboplastin time prolonged | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Alanine aminotransferase increased | 3/17 (17.6%) | 10/97 (10.3%) | 5/47 (10.6%) | 5/59 (8.5%) | ||||
| Aspartate aminotransferase increased | 1/17 (5.9%) | 3/97 (3.1%) | 5/47 (10.6%) | 2/59 (3.4%) | ||||
| Blood albumin decreased | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Blood alkaline phosphatase increased | 1/17 (5.9%) | 2/97 (2.1%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Blood bilirubin increased | 1/17 (5.9%) | 6/97 (6.2%) | 2/47 (4.3%) | 5/59 (8.5%) | ||||
| Blood phosphorus decreased | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Blood sodium increased | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Blood urea increased | 0/17 (0%) | 2/97 (2.1%) | 3/47 (6.4%) | 2/59 (3.4%) | ||||
| Body temperature fluctuation | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Liver function test abnormal | 1/17 (5.9%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Platelet count decreased | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Serum ferritin increased | 2/17 (11.8%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Weight decreased | 1/17 (5.9%) | 1/97 (1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 2/17 (11.8%) | 14/97 (14.4%) | 7/47 (14.9%) | 10/59 (16.9%) | ||||
| Dehydration | 0/17 (0%) | 2/97 (2.1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Hyperkalaemia | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Hypoalbuminaemia | 1/17 (5.9%) | 7/97 (7.2%) | 2/47 (4.3%) | 0/59 (0%) | ||||
| Hypocalcaemia | 1/17 (5.9%) | 4/97 (4.1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Hypokalaemia | 0/17 (0%) | 9/97 (9.3%) | 3/47 (6.4%) | 8/59 (13.6%) | ||||
| Hypomagnesaemia | 1/17 (5.9%) | 5/97 (5.2%) | 0/47 (0%) | 3/59 (5.1%) | ||||
| Hypophagia | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Hypophosphataemia | 1/17 (5.9%) | 2/97 (2.1%) | 0/47 (0%) | 2/59 (3.4%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/17 (5.9%) | 1/97 (1%) | 4/47 (8.5%) | 2/59 (3.4%) | ||||
| Back pain | 0/17 (0%) | 11/97 (11.3%) | 4/47 (8.5%) | 5/59 (8.5%) | ||||
| Pain in extremity | 0/17 (0%) | 6/97 (6.2%) | 5/47 (10.6%) | 2/59 (3.4%) | ||||
| Nervous system disorders | ||||||||
| Aphonia | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Balance disorder | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Dizziness | 2/17 (11.8%) | 9/97 (9.3%) | 4/47 (8.5%) | 2/59 (3.4%) | ||||
| Headache | 3/17 (17.6%) | 3/97 (3.1%) | 3/47 (6.4%) | 1/59 (1.7%) | ||||
| Mental impairment | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Poor quality sleep | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Syncope | 2/17 (11.8%) | 0/97 (0%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 1/17 (5.9%) | 2/97 (2.1%) | 0/47 (0%) | 2/59 (3.4%) | ||||
| Confusional state | 0/17 (0%) | 1/97 (1%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Initial insomnia | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Azotaemia | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Urinary incontinence | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Urinary retention | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Vaginal haemorrhage | 1/17 (5.9%) | 2/97 (2.1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disease | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Cough | 1/17 (5.9%) | 13/97 (13.4%) | 4/47 (8.5%) | 7/59 (11.9%) | ||||
| Dyspnoea | 1/17 (5.9%) | 9/97 (9.3%) | 5/47 (10.6%) | 4/59 (6.8%) | ||||
| Epistaxis | 5/17 (29.4%) | 27/97 (27.8%) | 11/47 (23.4%) | 12/59 (20.3%) | ||||
| Haemoptysis | 0/17 (0%) | 6/97 (6.2%) | 3/47 (6.4%) | 2/59 (3.4%) | ||||
| Oropharyngeal pain | 1/17 (5.9%) | 0/97 (0%) | 2/47 (4.3%) | 3/59 (5.1%) | ||||
| Productive cough | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Rales | 1/17 (5.9%) | 0/97 (0%) | 1/47 (2.1%) | 0/59 (0%) | ||||
| Sputum increased | 1/17 (5.9%) | 0/97 (0%) | 0/47 (0%) | 0/59 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Blood blister | 0/17 (0%) | 0/97 (0%) | 1/47 (2.1%) | 3/59 (5.1%) | ||||
| Decubitus ulcer | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 1/59 (1.7%) | ||||
| Dry skin | 0/17 (0%) | 1/97 (1%) | 0/47 (0%) | 3/59 (5.1%) | ||||
| Ecchymosis | 2/17 (11.8%) | 7/97 (7.2%) | 6/47 (12.8%) | 6/59 (10.2%) | ||||
| Petechiae | 6/17 (35.3%) | 41/97 (42.3%) | 11/47 (23.4%) | 8/59 (13.6%) | ||||
| Pruritus | 1/17 (5.9%) | 2/97 (2.1%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Purpura | 1/17 (5.9%) | 0/97 (0%) | 2/47 (4.3%) | 2/59 (3.4%) | ||||
| Rash | 1/17 (5.9%) | 0/97 (0%) | 1/47 (2.1%) | 1/59 (1.7%) | ||||
| Skin discolouration | 2/17 (11.8%) | 2/97 (2.1%) | 0/47 (0%) | 3/59 (5.1%) | ||||
| Skin haemorrhage | 0/17 (0%) | 2/97 (2.1%) | 3/47 (6.4%) | 0/59 (0%) | ||||
| Skin ulcer | 1/17 (5.9%) | 1/97 (1%) | 0/47 (0%) | 0/59 (0%) | ||||
| Vascular disorders | ||||||||
| Haematoma | 0/17 (0%) | 7/97 (7.2%) | 9/47 (19.1%) | 9/59 (15.3%) | ||||
| Haemorrhage | 2/17 (11.8%) | 4/97 (4.1%) | 4/47 (8.5%) | 1/59 (1.7%) | ||||
| Hypertension | 0/17 (0%) | 6/97 (6.2%) | 0/47 (0%) | 0/59 (0%) | ||||
| Hypotension | 1/17 (5.9%) | 3/97 (3.1%) | 1/47 (2.1%) | 2/59 (3.4%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01440374
Other Study ID Numbers:
- 114968
- 2011-000114-19
First Posted:
Sep 26, 2011
Last Update Posted:
Jun 5, 2017
Last Verified:
May 1, 2017