Clinical trial NCT00540423: Clinical Evaluation of SB-497115-GR in Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Official title: Clinical Evaluation of SB-497115-GR in Chronic Idiopathic Thrombocytopenic Purpura (ITP) -A Multicenter Study in Subjects With Chronic ITP Receiving a Double-Blind, Placebo-Controlled, Short-Term Treatment Followed by an Open-Label, Uncontrolled, Long-Term Treatment- <Phase II/III Study>
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Idiopathic Thrombocytopenic Purpura
Purpura, Thrombocytopenic, Idiopathic
Keywords: thrombopoietin,
immunosuppressive therapy,
eltrombopag,
idiopathic thrombocytopenic purpura,
blood platelet,
splenectomy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-08
Enrollment: 23
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase II/III multicenter study comprising of the double-blind, followed by open-label phases to evaluate and compare the efficacy and tolerability of eltrombopag (SB-497115-GR) in chronic ITP patients


Eligibility criteria: Inclusion criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria.

At Screening (Week -4 or -3)

* Diagnosed with ITP for at least 6 months prior to screening.
* Have a platelet count of \<30,000/µL.
* Previously treated refractory or relapsed patients who have failed to achieve a platelet count of \>=30,000/µL despite one or more prior therapies (either H. pylori eradication, corticosteroids, splenectomy, danazol or immunosuppressive drugs). (Note: Previous H. pylori eradication must have been completed at least 3 months prior to screening and clearly be ineffective).
* Previous treatment for ITP with splenectomy, rituximab, and cyclophosphamide must have been completed at Week -4 and clearly be ineffective.
* Subjects treated with cyclosporine A, mycophenolate mofetil or danazol must be receiving a dose that has been stable for at least 3 months prior to screening."
* A complete blood count (CBC) within the reference range, with the following exceptions

  1. Hemoglobin: females \>=9g/dL and males \>=10g/dL are eligible for inclusion if hemorrhage is present.
  2. Neutrophil count \>=1,500/µL (1.5x109/L) is required for inclusion.
* The following clinical chemistries MUST NOT exceed 1.2 times the normal reference range:creatinine, ALT, AST, total bilirubin and alkaline phosphatase.
* Albumin must be within 80 to 120% of normal range.
* Subject is \>=20 years old.
* Female subjects must either be:
* of non-childbearing potential (bilateral tubal ligation or post-menopausal), or
* of childbearing potential and have a negative pregnancy test and agree to use contraceptive methods specified in the GSK List of Highly Effective Methods for Avoidance of Pregnancy
* Hospitalization status: No restriction.
* Gender: No restriction.
* Subject has signed and dated written informed consent. At Randomization (Week 0)
* Have a platelet count of \<30,000/µL.
* Previous therapy for ITP with immunoglobulins (IVIG and anti-D) and vincristine must have been completed at least 2 weeks prior to randomization and the platelet count must show a clear downward trend after the last treatment with immunoglobulins.
* Subjects treated with corticosteroids or azathioprine must be receiving a dose that has been stable for at least 4 weeks prior to randomization.
* Prolongation of prothrombin time and activated partial thromboplastin time (aPTT) must not exceed 1.2 times the upper limit of the normal range with no history of hypercoagulable state. (Note: These parameters will be measured at screening or at randomization.)
* CBC and clinical chemistries fulfill the same criteria as those at screening.
* Reticulocyte count within the reference range or elevated in case of bleeding. (Note: This parameter will be measured at screening or at randomization.)

Exclusion criteria:

Subjects meeting any of the following criteria must not be enrolled in the study.

At Screening (Week -4 or -3)

* Any severe medical condition (cardiac, hepatic or renal disorder) other than chronic ITP. (Note: ""Severe"" is defined as \>=Grade 3 as a rule according to the ""Classification of the Severity of Adverse Experiences (PAB/SD Notification No.80, dated 29 June 1992) (Appendix X).)
* History of suspected or confirmed arterial or venous thrombosis (e.g., myocardial infarction, deep vein thrombosis) within the last 1 year.
* History of drug/alcohol abuse or dependence within 1 year prior to screening.
* Previous treatment with SB-497115-GR.
* Suspected blood disorder other than ITP.
* Suspected platelet aggregation abnormality.
* Suspected cyclic thrombocytopenia
* Current or history of HIV infection or hepatitis B virus or hepatitis C virus infections.
* Current or history of malignancy (Exception: Subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible).
* Female subjects who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period.
* Subjects who are deemed unsuitable for the study by the investigator (or sub investigator).
* Subjects who are participating in any other clinical trials at present or ones who previously participated in clinical trials and were treated with investigational products within last one month." At Randomization (Week 0)
* Subject wishes to withdraw consent.
* Subject is lost to follow-up.
* Subject has consumed anti-platelet agents (e.g., ticlopidine and aspirin), anticoagulants, or non-steroidal anti-inflammatory drugs (NSAIDs) for 7days prior to the first dose of study medication and will require these medications during the study period.
* Subjects who are deemed unsuitable for the study by the investigator (or sub investigator).

Primary outcomes:
measure: Number of Responders at Week 6
timeFrame: Week 6
measure: Percentage of Participants for Whom at Least 75% of Their Assessments During the Course of 26 Weeks of SB-497115-GR Treatment Met the Definition of Responders
timeFrame: Week 26
Secondary outcomes:
measure: Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6
timeFrame: Weeks 2 through 6
measure: Percentage of Responders at Each Visit
timeFrame: Days 8, 15, 22, 29, 36, and 43
measure: Mean Platelet Count at Each Visit
timeFrame: Baseline and Days 8, 15, 22, 29, 36, and 43
measure: Mean Change From Baseline in Platelet Counts at Each Visit
timeFrame: Baseline and Days 8, 15, 22, 29, 36, and 43
measure: Percentage of Participants With Bleeding Episodes Since the Last Visit
timeFrame: Days 1, 8, 15, 22, 29, 36, and 43
measure: Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category
timeFrame: Baseline and Days 8, 15, 22, 29, 36, and 43
measure: Percentage of Responders at Each Visit
timeFrame: Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
measure: Mean Platelet Counts of Participants at Each Visit
timeFrame: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
measure: Mean Change From Baseline in Platelet Counts at Each Visit
timeFrame: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
measure: Mean Maximum Duration for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter
timeFrame: Weeks 1 through 26
measure: Mean Total Time for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter
timeFrame: Weeks 1 through 26
measure: Percentage of Participants With Bleeding Episode Since the Last Visit
timeFrame: Days 1, 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
measure: Percentage of Participants With a Reduction in Dose and/or Number of Drugs of Concomitant ITP Medications From Baseline
timeFrame: Baseline through Week 26
measure: Percentage of Participants Who Received Rescue Treatment for ITP
timeFrame: Weeks 1 through 26
measure: Mean Number of Days of Concomitant ITP Medication Use Per Month
timeFrame: Weeks 1 through 26
measure: Pharmacokinetics of SB-497115-GR, Cmax
timeFrame: Week 9 or 10
measure: Pharmacokinetics of SB-497115-GR, Tmax
timeFrame: Week 9 or 10
measure: Pharmacokinetics of SB-497115, t1/2
timeFrame: Week 9 or 10
measure: Pharmacokinetics of SB-497115-GR, Lambda z
timeFrame: Week 9 or 10
measure: Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24
timeFrame: Week 9 or 10
measure: Pharmacokinetics of SB-497115-GR, CL/F
timeFrame: Week 9 or 10
measure: Pharmacokinetics of SB-497115-GR, Vz/F
timeFrame: Week 9 or 10
Other outcomes:
Locations:
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tomiyama Y, Miyakawa Y, Okamoto S, Katsutani S, Kimura A, Okoshi Y, Ninomiya H, Kosugi H, Nomura S, Ozaki K, Ikeda Y, Hattori T, Katsura K, Kanakura Y. A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J Thromb Haemost. 2012 May;10(5):799-806. doi: 10.1111/j.1538-7836.2012.04695.x.