AzTrials
AzTrials

Chronic Idiopathic Thrombocytopenic PurpuraPhase 3NCT00540423

Clinical Evaluation of SB-497115-GR in Chronic Idiopathic Thrombocytopenic Purpura (ITP)

A Phase 3 study testing SB-497115-GR 12.5mg, SB-497115-GR 25mg and SB-497115-GR 50 mg in people with Chronic Idiopathic Thrombocytopenic Purpura and Purpura, Thrombocytopenic, Idiopathic, run by GlaxoSmithKline at 7 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
SB-497115-GR 12.5mg, SB-497115-GR 25mg and SB-497115-GR 50 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
23 participants
Where
7 sitesJapan
Study dates
Sep 2007to Dec 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 25Show fewer
  • 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
  • Hemoglobin: females >=9g/dL and males >=10g/dL are eligible for inclusion if hemorrhage is present.
  • 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.)

Who cannot join

  • 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.
Show all 18Show fewer
  • 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).

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Japan7 sites

  • GSK Investigational Site

    Gifu, 503-8502

  • GSK Investigational Site

    Hiroshima, 734-8551

  • GSK Investigational Site

    Ibaraki, 305-8576

  • GSK Investigational Site

    Osaka, 565-0871

  • GSK Investigational Site

    Osaka, 596-8501

  • GSK Investigational Site

    Tochigi, 329-0498

  • GSK Investigational Site

    Tokyo, 160-8582

Other trials in Japan

About this study

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>

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

Being tested
SB-497115-GR 12.5mg, SB-497115-GR 25mg, SB-497115-GR 12.5mg matching placebo, SB-497115-GR 50 mg
Keywords
thrombopoietin,, immunosuppressive therapy,, eltrombopag,, idiopathic thrombocytopenic purpura,, blood platelet,, splenectomy
Medical subject headings
Purpura, Thrombocytopenic, Idiopathic, Jacobs syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SB-497115-GR 12.5mgDrug

    SB-497115-GR 12.5mg tablet once a day

  • SB-497115-GR 25mgDrug

    SB-497115-GR 25mg tablet once a day

  • SB-497115-GR 12.5mg matching placeboDrug

    SB-497115-GR 12.5mg matching placebo x1 or 2 tablet once a day

  • SB-497115-GR 50 mgDrug

    Also called SB-497115-GR 50mg

    SB-497115-GR 25mg tablet x2 once a day

Study groups in NCT00540423
Study groupRoleWhat they receive
SB-497115-GR groupExperimentalSubject will initiate treatment with SB-497115-GR 12.5mg once a day. Based on the subjects platelet count at each visit, the dose of SB-497115-GR may be adjusted at 12.5mg, 25mg or 50mg.
Receives: Drug: SB-497115-GR 12.5mg; Drug: SB-497115-GR 25mg; Drug: SB-497115-GR 50 mg
placebo groupPlacebo comparatorSubject will initiate treatment with SB-497115-GR 12.5mg matching placebo once a day. Based on the subjects platelet count at each visit, the dose of SB-497115-GR 12.5mg matching placebo may be increased to 2 tablet of SB-497115-GR 12.5mg matching placebo.
Receives: Drug: SB-497115-GR 12.5mg matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Responders at Week 6

    A responder was defined as a participant with a platelet count within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter).

    Measured: Week 6

  2. 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

    A responder was defined as a participant with a platelet count within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Week 26

Secondary outcomes (22)

  1. Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6

    A responder was defined as a participant with a platelet count within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter) at at least 4 out of 5 scheduled visits.

    Measured: Weeks 2 through 6

  2. Percentage of Responders at Each Visit

    A responder was defined as a participant with a platelet count within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter).

    Measured: Days 8, 15, 22, 29, 36, and 43

  3. Mean Platelet Count at Each Visit

    Blood taken from peripheral blood vessels was used for the measurement of platelet counts.

    Measured: Baseline and Days 8, 15, 22, 29, 36, and 43

  4. Mean Change From Baseline in Platelet Counts at Each Visit

    Change from baseline was calculated as values at Days 8, 15, 22, 29, 36, and 43 minus baseline value

    Measured: Baseline and Days 8, 15, 22, 29, 36, and 43

  5. Percentage of Participants With Bleeding Episodes Since the Last Visit

    When abnormal bleeding(s) was found since the last visit, it was recorded as a bleeding episode(s).

    Measured: Days 1, 8, 15, 22, 29, 36, and 43

  6. Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category

    Blood taken from peripheral blood vessels was used for the measurement of platelet counts.

    Measured: Baseline and Days 8, 15, 22, 29, 36, and 43

  7. Percentage of Responders at Each Visit

    A responder was defined as a participant with a platelet count within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26

  8. Mean Platelet Counts of Participants at Each Visit

    Blood taken from peripheral blood vessels was used for the measurement of platelet counts. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26

  9. Mean Change From Baseline in Platelet Counts at Each Visit

    Change from baseline was calculated as values at Days 8, 15, 22, 29, 36, and 43 and Weeks 10, 14, 18, 22, and 26 minus baseline value. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26

  10. Mean Maximum Duration for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter

    Maximum duration is measured as the longest period (days) for which a participant continuously maintained platelet counts within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Weeks 1 through 26

  11. Mean Total Time for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter

    Total time is measured as the cumulative number of days over which platelet counts were maintained within the target range (>=50 x 10^9/Liter and <=400 x 10^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Weeks 1 through 26

  12. Percentage of Participants With Bleeding Episode Since the Last Visit

    When abnormal bleeding(s) was found since the last visit, it was recorded as a bleeding episode(s). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Days 1, 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26

  13. Percentage of Participants With a Reduction in Dose and/or Number of Drugs of Concomitant ITP Medications From Baseline

    ITP medications are drugs, such as steroids or immunoglobulin, to be used for ITP. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Baseline through Week 26

  14. Percentage of Participants Who Received Rescue Treatment for ITP

    Rescue treatment for ITP is treatment applied to participants at high bleeding risk, such as those undergoing platelet transfusion or dose increase of steroids. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Weeks 1 through 26

  15. Mean Number of Days of Concomitant ITP Medication Use Per Month

    Cumulative number of days for which a participant received ITP medication during the treatment/total treatment period (months). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.

    Measured: Weeks 1 through 26

  16. Pharmacokinetics of SB-497115-GR, Cmax

    Cmax: Peak plasma concentration of SB-497115

    Measured: Week 9 or 10

  17. Pharmacokinetics of SB-497115-GR, Tmax

    tmax: Time when Cmax was achieved

    Measured: Week 9 or 10

  18. Pharmacokinetics of SB-497115, t1/2

    t1/2 is half life based on the terminal phase

    Measured: Week 9 or 10

  19. Pharmacokinetics of SB-497115-GR, Lambda z

    Lambda z is first order rate constant associated with the terminal portion of the plasma concentration curve.

    Measured: Week 9 or 10

  20. Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24

    AUC is area under a concentration vs. time curve.

    AUC0-24 (Area under the plasma concentration-time curve between 0 to 24 hrs) is calculated using the following equation:

    AUC0-24= AUClast + Clast × (1 - e-λz × [24-tlast])/λz. AUClast is AUC (area under a curve) computed to the last observation. Clast is concentration of last observation.

    Measured: Week 9 or 10

  21. Pharmacokinetics of SB-497115-GR, CL/F

    CL/F: CL is an estimate of the total body clearance, and F is the fraction of dose absorbed.

    Measured: Week 9 or 10

  22. Pharmacokinetics of SB-497115-GR, Vz/F

    VZ/F: VZ is the volume of distribution based on the terminal phase, and F is the fraction of dose absorbed.

    Measured: Week 9 or 10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionDec 2008
  4. Study completionDec 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00540423
Sponsor's protocol ID
108109
Status last verified
Mar 2011
First submitted
5 Oct 2007
Last updated
30 Mar 2011
Data monitoring committee
No

Publications

  • 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.

    PubMed 22409309

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SB-497115-GR 12.5mg, SB-497115-GR 25mg and SB-497115-GR 50 mg in people with Chronic Idiopathic Thrombocytopenic Purpura and Purpura, Thrombocytopenic, Idiopathic, run by GlaxoSmithKline at 7 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Responders at Week 6 (time frame: Week 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00540423, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2011.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in