A Pilot Study of a Thrombopoietin-Receptor Agonist, Eltrombopag, in Patients With Low to Int-2 Risk Myelodysplastic Syndrome (MDS)

Sponsor
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00961064
Collaborator
(none)
30
1
1
129.5
0.2

Study Details

Study Description

Brief Summary

Background:
  • Myelodysplastic syndromes (MDS) are bone marrow disorders characterized by anemia, neutropenia, and thrombocytopenia (low red blood cell, white blood cell, and platelet counts). Patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as a risk of progression to acute leukemia. Standard treatments for MDS have significant relapse rates. MDS patients with thrombocytopenia who fail standard therapies require regular, expensive, and inconvenient platelet transfusions, and are at risk for further serious bleeding complications.

  • Eltrombopag is a drug designed to mimic the protein thrombopoietin, which causes the body to make more platelets. Eltrombopag has been able to increase platelet counts in healthy volunteers and in patients with chronic ITP (a disease where patients destroy their own platelets very rapidly and thus develop thrombocytopenia), but researchers do not know if the drug can increase platelet counts in patients with MDS.

Objectives:
  • To find out whether eltrombopag can improve platelet counts in patients with MDS.

  • To determine whether eltrombopag is safe for patients with MDS.

Eligibility:
  • Patients 18 years of age and older who have consistently low blood platelet counts related to MDS that has not responded to conventional treatment.

  • Platelet count ≤ 30,000/μL or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); OR hemoglobin less than 9.0 gr/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry) OR ANC≤500

Design:
  • Treatment with eltrombopag tablets once per day for 16-20 weeks.

  • Participants will be monitored closely throughout the initial treatment, with weekly blood tests and separate evaluations at the National Institutes of Health (NIH) treatment center every 4 weeks. Bone marrow biopsies may be conducted to check for abnormalities in bone marrow.

  • If patients show signs of improved platelet counts after 90 days, treatment will continue with additional doses of eltrombopag.

  • Patients who discontinue taking eltrombopag will be evaluated at the NIH treatment center 4 weeks after ending treatment, and again 6 months after ending treatment to check for potential side effects.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The myelodysplastic syndromes (MDS) are bone marrow disorders characterized by anemia, neutropenia, and thrombocytopenia. Patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as a variable risk of progression to acute leukemia. With the exception of stem cell transplant, the standard treatments for MDS are rarely curative, and relapse rates are significant. MDS patients with cytopenias who fail standard therapies require regular blood or platelet transfusions which are expensive and inconvenient, and are at risk for serious bleeding complications.

Thrombopoietin (TPO) is the principal regulator of platelet production by megakaryocytes in the bone marrow. A 2nd generation TPO-agonist, eltrombopag (Promacta ) has been shown to increase platelets in thrombocytopenic patients with chronic immune thrombocytopenic purpura (ITP). Eltrombopag is administered orally, is well-tolerated, and is FDA approved for the treatment of thrombocytopenia in patients with chronic ITP who failed to respond to standard treatment.

Because the management of MDS patients with persistent cytopenias remains unsatisfactory and novel therapeutic approaches are needed, we propose a non-randomized, pilot, phase II study of eltrombopag in low to Int-2 risk MDS subjects with thrombocytopenia and anemia cytopenias who are either untreated or cytopenias that persist despite treatment with standard therapies to assess its utility in these settings.

Subjects will initiate study medication at an oral dose of 50 mg/day (25 mg/day for East Asians), which will be adjusted as clinically indicated to the lowest dose that maintains a stable platelet count greater than or equal to 20,000/microL above baseline while maximizing tolerability. Treatment response will be any increase in a cytopenia, in the lineage that fulfilled eligibility criteria for enrollment and will be defined as: (a) platelet count increases to 20,000/microL above baseline at 16 or 20 weeks , or stable platelet counts with transfusion independence for a minimum of 8 weeks in subjects who were previously transfusion dependent; (b) erythroid response for subjects with a pretreatment hemoglobin of less than 9 g/dL will be defined as an increase in hemoglobin by greater than or equal to 1.5g/dL without packed red blood cell (PRBC) transfusion support, or a reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment compared with the pretreatment transfusion number in the previous 8 weeks; (c) neutrophil response will be defined in those with a pretreatment absolute neutrophil count (ANC) of < 0.5 times 10(9)/L as at least a 100% increase or an absolute increase > 0.5 times 10(9)/L. Subjects meeting a response may remain on the extended access until they meet an off study criteria or the study is closed.

Subjects with response at 16 or 20 weeks may be consented for entry into the extended access part of the trial. In the event that a subject is transfused platelets for a count

10,000/microL without a medical indication during the study period, the subject may continue on study drug and the response assessment may be extended for an additional 4 weeks to week 20, at the discretion of the principal investigator. Subjects with evidence for a clinical response in any lineage at 16 weeks but not yet meeting full primary endpoint response criteria, and who are tolerating investigational treatment, may receive an additional 4 weeks of eltrombopag and be reassessed after 20 weeks. At that time, if they meet primary endpoint response criteria, they will be eligible to enter the extended access part of the study. If they do not meet primary endpoint response criteria, eltrombopag will be discontinued.

Primary objective is to assess the efficacy of eltrombopag in patients with low to Int-2 risk MDS. Safety of eltrombopag in this subject population will be assessed concurrently.

Secondary objectives include the toxicity profile of extended treatment with eltrombopag (treatment longer than 4 months), reduction in incidence and severity of bleeding episodes, and response following extended access to study drug (treatment longer than 4 months).

The primary endpoint will be the portion of drug responders as defined by changes in the platelet count and/or platelet transfusion requirements, or the proportion of subjects who meet erythroid response, or neutrophil response criteria.. Platelet response is defined as platelet count increases to 20,000/microL above baseline at 16 or 20 weeks, or stable platelet counts with transfusion independence for a minimum of 8 weeks. Erythroid response for subjects with a pretreatment hemoglobin of less than 9 g/dL will be defined as an increase in hemoglobin by greater than or equal to 1.5g/dL without packed red blood cell (PRBC) transfusion support, or a reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment compared with the pretreatment transfusion number in the previous 8 weeks. Neutrophil response will be defined in those with a pretreatment absolute neutrophil count (ANC) of <0.5 times 10(9)/L as at least a 100% increase or an absolute increase > 0.5 times 10(9)/L. Subjects with an erythroid, and/or neutrophil response at 16 weeks may continue study medication (extended access) until they meet an off study criteria. Subjects with erythroid, or neutrophil response at 16 weeks may continue study medication for an additional 4 weeks (to ensure eligibility) prior to being consented for entry into the extended access part of the trial. Patients may remain on the extended access until they met an off study criteria.

The toxicity profile will be measured using the CTCAE Version 4.0 criteria.

Secondary endpoints will include incidence of grade 2 or higher bleeding events as measured by CTCAE v. 4.0; changes in serum thrombopoietin level, measured at 4 months; and progression to higher risk MDS as measured by IWG criteria.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Patients With Low to Int-2 Risk Myelodysplastic Syndrome (MDS)
Actual Study Start Date :
Mar 15, 2011
Actual Primary Completion Date :
Aug 10, 2017
Actual Study Completion Date :
Dec 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)

Eltrombopag will be initiated at 50 mg/day (Asians 25 mg/day) and dose adjusted up to 150mg/day based response and safety in participants with Low to Int-2 Risk Myelodysplastic Syndrome (MDS)

Drug: Eltrombopag
Eltrombopag will be initiated at 50 mg/day (Asians 25 mg/day) and dose adjusted up to 150mg/day based response and safety
Other Names:
  • PROMACTA
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Response Between Weeks 16 and 20 [16-20 weeks]

      The primary endpoint was hematologic response at 16 or 20 weeks, defined as either: (1) an increase in platelet counts =20.000/uL or transfusion independence for a minimum of 8 weeks; (2) hemoglobin (Hb) increase of =1.5g/dL from baseline, or a reduction in red blood cells (RBC) transfusion of at least 50%; or (3) an increase in absolute neutrophil counts (ANC) of =0.5x109/L or by at least 100% in patients with a baseline ANC <0.5x109/L.

    Secondary Outcome Measures

    1. Changes in Serum Thrombopoietin Level [16-20 weeks]

      Changes in serum thrombopoietin level in participants With Low to Int-2 Risk Myelodysplastic Syndrome (MDS) following Eltrombopag

    2. Number of Participants With Progression to Higher Risk Myelodysplastic Syndrome as Measured by International Working Group Criteria [up to 5 years]

      Number of participants with progression to higher risk Myelodysplastic syndrome (MDS) as measured by International Working Group (IWG) 2006 criteria in participants With Low to Int-2 Risk Myelodysplastic Syndrome (MDS) following Eltrombopag. Progression of disease per modified IWG criteria 2006 were considered: if patients with baseline bone marrow blasts of < 5% increase by ≥ 50% to >5% blasts; and either at least 50% decrease in granulocytes or platelets from maximum response, decreasing in Hb by 2g/dL or transfusion dependence. The acquisition of new cytogenetic abnormality without meeting other IWG criteria for progression was not considered disease progression.

    3. Number of Participants Who Achieved a Robust Response and Discontinued Eltrombopag [up to 5 years]

      Number of participants who achieved a robust response and discontinued Eltrombopag in extended access A robust response is defined as: as platelets >50,000/μL, hemoglobin > 10 g/dL in the absence of transfusions, and neutrophils > 1,000 for more than 8 weeks.

    4. Number of Participants With Grade 2 or Higher Bleeding Events Defined by Common Terminology Criteria for Adverse Events v. 4.0 [up to 5 years]

      Number of Participants with Grade 2 or Higher Bleeding Events defined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The NCI CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Grade 1 Mild is asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 is moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)*. Grade 3 is severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**. Grade 4 if life-threatening consequences; urgent intervention indicated. Grade 5 is death related to AE.

    Eligibility Criteria

    Criteria

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

    Diagnosis of MDS, with WHO classification of refractory anemia, refractory cytopenia with unilineage dysplasia (RCUD), RARS, RCMD-RS, or RCMD.

    IPSS risk scores of low, intermediate-1, or intermediate-2.

    Platelet count less than or equal to 30,000/ microL or platelet-transfusion-dependence (requiring at least 4 platelet transfusions in the 8 weeks prior to study entry); or hemoglobin less than 9.0 gr/dL or red cell transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior to study entry) OR ANC less than or equal to 500

    Age greater than or equal to 18 years old

    Treatment naive or off all other treatments for MDS (except stable dosing of filgrastim [G-CSF], erythropoietin, and transfusion support) for at least four weeks. G-CSF can be used before, during and after the protocol treatment for subjects with documented neutropenia (<500/UI) as long as they meet the criteria for other cytopenia as stated above. G-CSF must be held for 3 weeks prior to enrollment bone marrow biopsy and prior to each study assessment bone marrow biopsy, unless clinically indicated to avoid infections per PI discretion.

    Adequate liver function, as evidenced by total serum bilirubin less than or equal to 1.5 times the upper limit of normal patients with Gilbert's disease are eligible, provided intermittent indirect hyperbilirubinemia, AST or ALT less than or equal to 5 times the upper limit of normal.

    A serum creatinine concentration less than or equal to 2 times ULN

    EXCLUSION CRITERIA:

    WHO classification of chronic myelomonocytic leukemia (CMML), RAEB-1, RAEB-2, AML

    Treatment with horse or rabbit ATG or Campath within 6 months of study entry

    Subjects with liver cirrhosis including subjects infected with Hepatitis B or C

    Subjects with HIV

    Infection not adequately responding to appropriate therapy

    History of malignancy treated with chemotherapy and cytogenetic abnormalities suggestive of secondary myelodysplasia.

    Moribund status or concurrent hepatic, renal, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy

    Life expectancy of less than 3 months

    Hypersensitivity to eltrombopag or its components

    Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential

    Unable to understand the investigational nature of the study or give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent per section

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Neal S Young, M.D., National Heart, Lung, and Blood Institute (NHLBI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    National Heart, Lung, and Blood Institute (NHLBI)
    ClinicalTrials.gov Identifier:
    NCT00961064
    Other Study ID Numbers:
    • 090199
    • 09-H-0199
    First Posted:
    Aug 18, 2009
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Mar 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by National Heart, Lung, and Blood Institute (NHLBI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Period Title: Initial Treatment (Weeks 1 - 20)
    STARTED 30
    COMPLETED 14
    NOT COMPLETED 16
    Period Title: Initial Treatment (Weeks 1 - 20)
    STARTED 14
    COMPLETED 7
    NOT COMPLETED 7

    Baseline Characteristics

    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Overall Participants 30
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    15
    50%
    >=65 years
    15
    50%
    Sex: Female, Male (Count of Participants)
    Female
    9
    30%
    Male
    21
    70%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    3.3%
    Not Hispanic or Latino
    29
    96.7%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    4
    13.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    13.3%
    White
    19
    63.3%
    More than one race
    1
    3.3%
    Unknown or Not Reported
    2
    6.7%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Response Between Weeks 16 and 20
    Description The primary endpoint was hematologic response at 16 or 20 weeks, defined as either: (1) an increase in platelet counts =20.000/uL or transfusion independence for a minimum of 8 weeks; (2) hemoglobin (Hb) increase of =1.5g/dL from baseline, or a reduction in red blood cells (RBC) transfusion of at least 50%; or (3) an increase in absolute neutrophil counts (ANC) of =0.5x109/L or by at least 100% in patients with a baseline ANC <0.5x109/L.
    Time Frame 16-20 weeks

    Outcome Measure Data

    Analysis Population Description
    The first 5 subjects enrolled were not counted toward the accrual target due to changes in protocol.
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Measure Participants 25
    Count of Participants [Participants]
    11
    36.7%
    2. Secondary Outcome
    Title Changes in Serum Thrombopoietin Level
    Description Changes in serum thrombopoietin level in participants With Low to Int-2 Risk Myelodysplastic Syndrome (MDS) following Eltrombopag
    Time Frame 16-20 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Measure Participants 30
    Median (Full Range) [pg/mL]
    2080
    3. Secondary Outcome
    Title Number of Participants With Progression to Higher Risk Myelodysplastic Syndrome as Measured by International Working Group Criteria
    Description Number of participants with progression to higher risk Myelodysplastic syndrome (MDS) as measured by International Working Group (IWG) 2006 criteria in participants With Low to Int-2 Risk Myelodysplastic Syndrome (MDS) following Eltrombopag. Progression of disease per modified IWG criteria 2006 were considered: if patients with baseline bone marrow blasts of < 5% increase by ≥ 50% to >5% blasts; and either at least 50% decrease in granulocytes or platelets from maximum response, decreasing in Hb by 2g/dL or transfusion dependence. The acquisition of new cytogenetic abnormality without meeting other IWG criteria for progression was not considered disease progression.
    Time Frame up to 5 years

    Outcome Measure Data

    Analysis Population Description
    intention to treat analysis
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Measure Participants 30
    Count of Participants [Participants]
    6
    20%
    4. Secondary Outcome
    Title Number of Participants Who Achieved a Robust Response and Discontinued Eltrombopag
    Description Number of participants who achieved a robust response and discontinued Eltrombopag in extended access A robust response is defined as: as platelets >50,000/μL, hemoglobin > 10 g/dL in the absence of transfusions, and neutrophils > 1,000 for more than 8 weeks.
    Time Frame up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Analysis included those participants that participated in extended access portion of study
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Measure Participants 14
    Count of Participants [Participants]
    10
    33.3%
    5. Secondary Outcome
    Title Number of Participants With Grade 2 or Higher Bleeding Events Defined by Common Terminology Criteria for Adverse Events v. 4.0
    Description Number of Participants with Grade 2 or Higher Bleeding Events defined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The NCI CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline. Grade 1 Mild is asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 is moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)*. Grade 3 is severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**. Grade 4 if life-threatening consequences; urgent intervention indicated. Grade 5 is death related to AE.
    Time Frame up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    Measure Participants 30
    Count of Participants [Participants]
    5
    16.7%

    Adverse Events

    Time Frame Up to 5 years
    Adverse Event Reporting Description Any observed or volunteered adverse events that are as listed in the Eltrombopag Package Insert and/or Investigator's Brochure will not be reported unless (1) the adverse event was not present at baseline exam; (2) the adverse event is previously unknown (not on the label); (3) the adverse event is more severe than on the label; (4) the frequency of the adverse events increases above the listed frequency; or (5) meets the criteria for a serious adverse event.
    Arm/Group Title Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Arm/Group Description Eltrombopag (EPAG), a thrombopoietin receptor agonist, was started at 50 mg/day, up to a maximal dose of 150 mg/day, increasing the dose by 25mg every 2 weeks.
    All Cause Mortality
    Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Affected / at Risk (%) # Events
    Total 1/30 (3.3%)
    Serious Adverse Events
    Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Affected / at Risk (%) # Events
    Total 12/30 (40%)
    General disorders
    Death 1/30 (3.3%)
    Injury, poisoning and procedural complications
    Fall 1/30 (3.3%)
    Investigations
    Investigation 1/30 (3.3%)
    Nervous system disorders
    Nervous system disorder 1/30 (3.3%)
    Renal and urinary disorders
    Bladder mass 1/30 (3.3%)
    Surgical and medical procedures
    Hospitalisation 10/30 (33.3%)
    Other (Not Including Serious) Adverse Events
    Eltrombopag in Low to Int-1 Risk Myelodysplastic Syndrome (MDS)
    Affected / at Risk (%) # Events
    Total 28/30 (93.3%)
    Blood and lymphatic system disorders
    Febrile neutropenia 2/30 (6.7%)
    Jaundice 4/30 (13.3%)
    Ocular icterus 4/30 (13.3%)
    Petechiae 3/30 (10%)
    Cardiac disorders
    Dizziness 7/30 (23.3%)
    Dyspnoea 6/30 (20%)
    Oedema peripheral 2/30 (6.7%)
    Eye disorders
    Blepharospasm 2/30 (6.7%)
    Vision blurred 2/30 (6.7%)
    Gastrointestinal disorders
    Abdominal discomfort 4/30 (13.3%)
    Abdominal pain 5/30 (16.7%)
    Constipation 5/30 (16.7%)
    Diarrhoea 6/30 (20%)
    Faeces discoloured 2/30 (6.7%)
    Flatulence 2/30 (6.7%)
    Gastrooesophageal reflux disease 2/30 (6.7%)
    Gingival bleeding 4/30 (13.3%)
    Nausea 6/30 (20%)
    Oropharyngeal pain 3/30 (10%)
    Stomatitis 2/30 (6.7%)
    Toothache 2/30 (6.7%)
    Vomiting 2/30 (6.7%)
    General disorders
    Asthenia 3/30 (10%)
    Chills 2/30 (6.7%)
    Fatigue 11/30 (36.7%)
    Flank pain 2/30 (6.7%)
    Oedema 3/30 (10%)
    Pain 3/30 (10%)
    Pyrexia 2/30 (6.7%)
    Infections and infestations
    Bronchitis 2/30 (6.7%)
    Sinusitis 3/30 (10%)
    Upper respiratory tract infection 7/30 (23.3%)
    Urinary tract infection 2/30 (6.7%)
    Injury, poisoning and procedural complications
    Contusion 4/30 (13.3%)
    Investigations
    Haemoglobin decreased 9/30 (30%)
    Liver function test increased 3/30 (10%)
    Neutrophil count decreased 7/30 (23.3%)
    Platelet count decreased 7/30 (23.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/30 (16.7%)
    Musculoskeletal pain 3/30 (10%)
    Musculoskeletal stiffness 2/30 (6.7%)
    Pain in extremity 2/30 (6.7%)
    Nervous system disorders
    Aphasia 2/30 (6.7%)
    Headache 6/30 (20%)
    Insomnia 2/30 (6.7%)
    Paraesthesia 3/30 (10%)
    Psychiatric disorders
    Anxiety 2/30 (6.7%)
    Depression 2/30 (6.7%)
    Renal and urinary disorders
    Chromaturia 2/30 (6.7%)
    Haematuria 3/30 (10%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/30 (16.7%)
    Skin and subcutaneous tissue disorders
    Pruritus 2/30 (6.7%)
    Rash 4/30 (13.3%)
    Skin discolouration 3/30 (10%)
    Skin lesion 5/30 (16.7%)
    Surgical and medical procedures
    Sinus operation 2/30 (6.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Bhavisha Patel, MD
    Organization National Heart Lung and Blood Institute
    Phone 301.402.3477
    Email bhavisha.patel@nih.gov
    Responsible Party:
    National Heart, Lung, and Blood Institute (NHLBI)
    ClinicalTrials.gov Identifier:
    NCT00961064
    Other Study ID Numbers:
    • 090199
    • 09-H-0199
    First Posted:
    Aug 18, 2009
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Mar 1, 2021