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Eltrombopag

Phase 3

Hepatitis C | Small molecule | Infectious Disease |GSK plc|Last Updated: Oct 12, 2018

Success Probability

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Market & Valuation

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Trial Design

ACTIVE_CONTROLLED
Total Trials2
Total Enrollment67

FDA Designations

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Clinical trial landscape

Eltrombopag · 18 trials · 8 indications

Phase 3 6Phase 2 2Phase 1 10
NCT01520909Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body.Idiopathic Thrombocytopenic Purpura
COMPLETED92 Analytics
NCT00996216Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390Hepatitis C
COMPLETED27 Analytics
NCT00828750Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP)Idiopathic Thrombocytopenic Purpura
COMPLETED19 Analytics
NCT00529568Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver DiseaseHepatitis C, Chronic
COMPLETED759 Analytics
NCT00516321Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver DiseaseHepatitis C, Chronic
COMPLETED687 Analytics
NCT00370331RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With EltrombopagPurpura, Thrombocytopaenic, Idiopathic
COMPLETED197 Analytics
PHASE3COMPLETED
Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body.
Idiopathic Thrombocytopenic PurpuraUnlock trial analytics
PHASE3COMPLETED
Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390
Hepatitis CUnlock trial analytics
PHASE3COMPLETED
Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Idiopathic Thrombocytopenic PurpuraUnlock trial analytics
PHASE3COMPLETED
Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease
Hepatitis C, ChronicUnlock trial analytics
PHASE3COMPLETED
Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver Disease
Hepatitis C, ChronicUnlock trial analytics
PHASE3COMPLETED
RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag
Purpura, Thrombocytopaenic, IdiopathicUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) for at Least 6 Out of 8 Weeks, Between Weeks 5 and 12 of Part 1
From Week 5 up to Week 12 of Part 1

Participants who achieved a platelet count \>=50 Gi/L for at least 6 out of 8 weeks, between Weeks 5 and 12 of Part 1, were reported.

Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1
From the start of investigational product up to the start of antiviral therapy (up to 9 weeks; median of 21 days)

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.

Number of Participants With Any AE and Any SAE in Part 2
From the date of initiation of antiviral therapy (Antiviral Baseline Visit [between Study Day 14 and Study Day 65]) to the completion of the follow-up period (up to Week 96/WD)

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.

Number of Participants With the Indicated Worst-case Division of Acquired Immune Deficiency Syndrome (DAIDS) Grade Increases From Screening for the Indicated Clinical Chemistry Parameters During Part 1
From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)

Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Clinical Chemistry Parameter During Part 2
From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD)

Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

Number of Participants With the Indicated Worst-case DAIDS Grade Increases From Screening for the Indicated Hematology Parameters During Part 1
From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)

Blood samples were collected for the measurement of hematology parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Hematology Parameters During Part 2
From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD)

Blood samples were collected for the measurement of hematology chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

Number of Participants With a Decrease in Visual Acuity During Parts 1 and 2
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)

Visual acuity (VA) is defined as acuteness or clearness of vision.

Number of Participants With the Indicated Change in logMAR Scale Values During Parts 1 and 2
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)

LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.

Number of Participants With a logMAR Change >=0.15 During Parts 1 and 2
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)

LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.

Number of Participants Experiencing an Adverse Event (AE) and/or Serious Adverse Event (SAE) Within the Indicated Category
From Baseline (Day 1) to last dose of eltrombopag/early withdrawal visit (up to 981 days)

An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medical product, whether or not related to the product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or its prolongation, results in disability/incapacity, is a congenital anomaly/birth defect, or is another event considered serious. A drug-related AE is any AE that was judged to have a relationship with the study medication by the investigator. The severity of an AE is based on the investigator's clinical judgment.

Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase
From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Participants with SVR are defined as those with non-detectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at the end of treatment and all subsequent planned visits up to 24 weeks post-completion of the treatment period of the DB Phase.

Percentage of Responders
Baseline; each on-therapy treatment day; Weeks 10, 14, 18, 22, and 26; and Weeks 1, 2, and 4 post-treatment

The percentage of evaluable participants who achieved a platelet response (defined as a platelet count between 50,000 and 400,000 microliter) at each nominal on-therapy day and 4 weeks post-treatment

Percentage of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) at Least Once, Between Day 8 and Day 43 (Weeks 1 to 6) of the Randomized Period of the Study (Part 2)
From Day 8 up to Day 43 of Part 2

Participants who achieved a platelet count \>=50 Gi/L at least once between Day 8 and Day 43 (first 6 weeks of Part 2) in the absense of rescue treatment were reported. A 95% confidence interval was calculated by the exact binomial method.

Number of Participants Who Responded (Platelet Count >=50 Gi/L and >=2x Baseline) to Eltrombopag Treatment in Cycle 2 or Cycle 3 Given Participants Responded in Cycle 1
Day 42 of each cycle

Complete blood count, platelet count by blood draw

Plasma eltrombopag area under time-concentration curve from time zero to infinity (AUC[0-inf])
Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose in each treatment period
Plasma eltrombopag maximum observed concentration (Cmax)
Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose in each treatment period
Composite of PK parameters for eltrombopag
Serum Pharmacokinetic (PK) samples will be collected pre-dose and then samples will be obtained 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12, 16, 24, 48, 72 and 96 hours after drug administration

Following PK parameters will be assessed: Area under the concentration-time curve from time zero to last time of quantifiable concentration within a subject (AUC\[0-t\]), area under the curve (concentration/time) from time 0 extrapolated to infinity (AUC\[0 inf\]), maximum observed concentration (Cmax) and time to Cmax (tmax)

Composite pharmacokinetic (PK) parameters of eltrombopag following administration of boceprevir for 10 days with a single dose of eltrombopag
For 17 days

Plasma eltrombopag PK Parameters: area under the concentration time-curves from time zero to infinity AUC(0-infinity) and maximum concentration (Cmax).

Composite PK parameters of boceprevir following administration of boceprevir for 10 days with a single dose of eltrombopag
For 17 days

Plasma boceprevir PK Parameters: AUC from time zero to the dosing interval AUC(0-τ), Cmax, and Concentraction at end of the dosing interval (Cτ)

Composite PK parameters of eltrombopag following administration of telaprevir for 10 days with a single dose of eltrombopag
For 17 days

Plasma eltrombopag PK Parameters: AUC(0-infinity) and Cmax

Composite PK parameters of telaprevir following administration of telaprevir for 10 days with a single dose of eltrombopag
For 17 days

Plasma telaprevir PK Parameters: AUC(0-τ), Cmax, and Cτ.

Evaluate the relative bioavailability of a PfOS formulation relative to the commercial eltrombopag 25 mg tablet formulation in healthy adult subjects.
72 hours x 2 periods
Evaluate the effect of a high calcium, moderate fat and calorie meal on the pharmacokinetics of a single oral 25 mg dose of eltrombopag PfOS in healthy adult subjects when eltrombopag is administered concurrently, two hours before, or two hours afte
72 hours x 3 periods
Pharmacokinetic parameters per the protocol
sixteen days
Evaluate the photosensitizing potential, as measured by photoirritant index and change from baseline in minimum erythemal dose, of eltrombopag when dosed orally at 75 mg QD as compared to placebo and ciprofloxacin 500 mg BID.
Screening - Day 8
To establish a taste preference of eltrombopag in a pediatric formulation taken at initial dosing, 3hours, and 6 hours on Day 1 & 2.
at initial dosing, 3hours, and 6 hours on Day 1 & 2.
Plasma levels and protein binding of eltrombopag
at Day 1 to Day 6.

plasma levels/protein binding for eltrombopag

Safety and tolerability endpoints will consist of the evaluation of adverse events (AE), and changes from baseline in vital signs and clinical laboratory parameters
Approximately 42 weeks

Secondary Endpoints

Percentage of Responders
From Week 1 up to Week 12 of Part 1
Number of Participants Achieving a Platelet Count >=50 Gi/L at Any Time During the First 12 Weeks of Part 1
From Baseline up to Week 12 of Part 1
Number of Participants Achieving a Platelet Count >=50 Gi/L at Any Time During the First 6 Weeks of Part 1
From Baseline up to Week 6 of Part 1
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Eltrombopag plus standard of careEXPERIMENTALPart 1, double-blind treatment group
Placebo plus standard of carePLACEBO_COMPARATORPart 1, double-blind treatment group
Eltrombopag plus standard of care (Part 2 open-label)EXPERIMENTALPart 2, open-label
Open-label eltrombopagEXPERIMENTALOpen-label eltrombopag with dose titrations to support adequate platelet counts.
TreatmentEXPERIMENTALEltrombopag oral tablets once daily
eltrombopagEXPERIMENTALactive treatment arm
placeboPLACEBO_COMPARATORplacebo control arm
Treatment arm plus standard of careEXPERIMENTALSubjects will initiate treatment with 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down.
SEQUENCE D0, D1, D2EXPERIMENTALParticipants will receive treatment D0 in treatment period 1, D1 in treatment period 2 and D2 in treatment period 3 (one treatment per period). Where D0=eltrombopag 50 milligram (mg), D1= cyclosporine 200 mg + eltrombopag 50 mg, and D2= cyclosporine 600 mg + eltrombopag 50 mg. Treatment periods will be separated by washout periods of 3-10 days
SEQUENCE D1, D0, D2EXPERIMENTALParticipants will receive treatment D1 in treatment period 1, D0 in treatment period 2 and D2 in treatment period 3 (one treatment per period). Where D0=eltrombopag 50 mg, D1= cyclosporine 200 mg + eltrombopag 50 mg, and D2= cyclosporine 600 mg + eltrombopag 50 mg. Treatment periods will be separated by washout periods of 3-10 days
SEQUENCE D1, D2, D0EXPERIMENTALParticipants will receive treatment D1 in treatment period 1, D2 in treatment period 2 and D0 in treatment period 3 (one treatment per period). Where D0=eltrombopag 50 mg, D1= cyclosporine 200 mg + eltrombopag 50 mg, and D2= cyclosporine 600 mg + eltrombopag 50 mg. Treatment periods will be separated by washout periods of 3-10 days
Eltrombopag 50 mgEXPERIMENTALEach volunteer will receive orally, single dose of tablet eltrombopag 50 mg under fasting conditions
BoceprevirEXPERIMENTALSubjects will receive boceprevir 800 mg orally every 8 hours (hrs) for 10 days in Period 2 with moderate-fat meals.
TelaprevirEXPERIMENTALSubjects will receive telaprevir 750 mg orally every 8 hours hrs for 10 days in Period 2 with moderate-fat meals.
Eltrombopag and BroceprevirEXPERIMENTALSubjects will receive eltrombopag 200 mg as single oral dose and boceprevir 800 mg orally every 8 hrs for a day in Period 3 with moderate-fat meals.
Eltrombopag and TelaprevirEXPERIMENTALSubjects will receive eltrombopag 200 mg as single oral dose and telaprevir 750 mg orally every 8 hrs for a day in Period 3 with moderate-fat meals.
Arm BEXPERIMENTAL25 mg powder for oral suspension single dose fasted.
Arm CEXPERIMENTAL25 mg powder for oral suspension administered with a meal
Arm DEXPERIMENTAL25 mg powder for oral suspension administered 2 hours prior to meal
Arm EEXPERIMENTAL25 mg powder for oral suspension administered 2 hours after to meal
Arm AOTHERCommercially available eltrombopag 25 mg tablet
Period 2ACTIVE_COMPARATORTreatment B
Period 1ACTIVE_COMPARATORTreatment A
Period 3ACTIVE_COMPARATORTreatment C
Arm 1EXPERIMENTALEltrombopag 75 mg QD x 6 days
Arm 2ACTIVE_COMPARATORCiprofloxicin 500mg BID x 6 days
Arm 3PLACEBO_COMPARATORPlacebo QD x 6 days
Group BEXPERIMENTALGroup B is a dose escalation phase designed to determine the optimal biological dose of eltrombopag in subjects with sarcoma who received chemotherapy treatment with Adriamycin and Ifosfamide
Group AEXPERIMENTALGroup A will be used for further exploration of the optimal biological dose (as initially established by completion of Group B), by using 2 different dosing schedules of eltrombopag.
Healthy subjectsACTIVE_COMPARATORSubjects will receive a single 50 mg oral dose of eltrombopag.
Subjects with hepatic impairmentEXPERIMENTALSubjects with mild, moderate or severe hepatic impairment will receive a single 50 mg oral dose of eltrombopag.

Interventions

NameTypeDescription
EltrombopagDRUGThrombopoietin receptor agonist
PlaceboDRUGPlacebo with no active pharmaceutical ingredient
Antiviral therapyDRUGCombination of either peginterferon alfa-2a or alfa-2b with ribavirin at investigator's discretion.
Eltrombopag oral tabletsDRUGEltrombopag oral tablets once daily
CyclosporineDRUGSoft gelatine capsule containing cyclosporine 100 mg for oral administration. Cyclosporine will be administered at the doses of 200 mg (2 x 100 mg capsules) or 600 mg (6 x 100 mg capsules)
BoceprevirDRUGEach capsule contains 200 mg of Boceprevir (Dose 800 mg)
TelaprevirDRUGEach tablet contains 375 mg of Telaprevir (Dose 750 mg)
Lopinavir/RitonavirDRUGLopinavir/Ritonavir 400/100 mg oral dose given twice a day for 14 days
Eltrombopag and Lopinavir/RitonavirDRUGElrombopag 100 mg single oral dose and Lopinavir/Ritonavir 400/100 mg oral dose given in the AM and PM
CiprofloxacinDRUGGiven 500mg BID x 6 days
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Eligibility Criteria

Age Range1 Year to 17 Years
SexALL
Healthy VolunteersNo
Study Sites51

Inclusion Criteria: * Written informed consent must be obtained from the patient's guardian and accompanying informed assent from the patient (for children over 6 years old) * Patients must be between 1 year and \<18 years of age at Day 1 * Patients will have a confirmed diagnosis of chronic ITP fo...

Countries:United StatesArgentinaCzechiaGermanyHong KongIsraelItalyPolandRussiaSpainTaiwanThailandUnited KingdomAustraliaCanadaFranceGreecePakistanJapanBelgiumBrazilEgyptIndiaPuerto RicoRomaniaSlovakiaSouth KoreaUkraineNetherlandsAustriaChinaDenmarkFinlandNew ZealandPeruTunisiaVietnamMexico
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Competitive Landscape -Hepatitis C 11 trials

Frequently asked questions about Eltrombopag

What is Eltrombopag used for?

Eltrombopag is a small molecule being studied for use in idiopathic thrombocytopenic purpura, a condition of low platelet counts, as well as in healthy subjects and in patients with liver cirrhosis. It has also been investigated in the context of hepatitis C. The drug is in clinical development and is not yet approved.

Who makes Eltrombopag?

Eltrombopag is being developed by GSK plc, which trades under the ticker GSK. The company has conducted multiple clinical trials of the drug across various patient populations, including healthy volunteers and patients with hepatic impairment or hepatitis C.

What phase is Eltrombopag in?

Eltrombopag is in Phase 1 clinical development. A total of seven trials have been completed, with no active trials currently ongoing. The completed trials include Phase 1 studies in healthy subjects and patients with hepatic impairment, as well as a Phase 3 study in non-responders to earlier eltrombopag studies.

What clinical trials is Eltrombopag in?

Eltrombopag has been studied in several completed clinical trials, including NCT00359463 in healthy subjects and volunteers with mild, moderate, or severe hepatic impairment, NCT00833378 a drug interaction study with lopinavir/ritonavir in healthy adults, NCT00996216 in non-responders to prior eltrombopag studies, and NCT02254434 a pharmacokinetic study in healthy volunteers under fasting conditions.

Is Eltrombopag the same as other names?

Eltrombopag is the drug name used across the clinical trials. No alternative names have been reported for this asset. It is a small molecule therapeutic being developed by GSK plc for conditions related to low platelet counts and liver disease.