- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00540423
Clinical Evaluation of SB-497115-GR in Chronic Idiopathic Thrombocytopenic Purpura (ITP)
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 Overview
Status
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Gifu, Japan, 503-8502
- GSK Investigational Site
-
Hiroshima, Japan, 734-8551
- GSK Investigational Site
-
Ibaraki, Japan, 305-8576
- GSK Investigational Site
-
Osaka, Japan, 596-8501
- GSK Investigational Site
-
Osaka, Japan, 565-0871
- GSK Investigational Site
-
Tochigi, Japan, 329-0498
- GSK Investigational Site
-
Tokyo, Japan, 160-8582
- GSK Investigational Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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.)
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: SB-497115-GR group
Subject 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.
|
SB-497115-GR 12.5mg tablet once a day
SB-497115-GR 25mg tablet once a day
SB-497115-GR 25mg tablet x2 once a day
Other Names:
|
PLACEBO_COMPARATOR: placebo group
Subject 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.
|
SB-497115-GR 12.5mg matching placebo x1 or 2 tablet once a day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Responders at Week 6
Time Frame: 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).
|
Week 6
|
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
Time Frame: Week 26
|
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.
|
Week 26
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6
Time Frame: Weeks 2 through 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.
|
Weeks 2 through 6
|
Percentage of Responders at Each Visit
Time Frame: Days 8, 15, 22, 29, 36, and 43
|
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).
|
Days 8, 15, 22, 29, 36, and 43
|
Mean Platelet Count at Each Visit
Time Frame: Baseline and Days 8, 15, 22, 29, 36, and 43
|
Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
|
Baseline and Days 8, 15, 22, 29, 36, and 43
|
Mean Change From Baseline in Platelet Counts at Each Visit
Time Frame: Baseline and Days 8, 15, 22, 29, 36, and 43
|
Change from baseline was calculated as values at Days 8, 15, 22, 29, 36, and 43 minus baseline value
|
Baseline and Days 8, 15, 22, 29, 36, and 43
|
Percentage of Participants With Bleeding Episodes Since the Last Visit
Time Frame: Days 1, 8, 15, 22, 29, 36, and 43
|
When abnormal bleeding(s) was found since the last visit, it was recorded as a bleeding episode(s).
|
Days 1, 8, 15, 22, 29, 36, and 43
|
Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category
Time Frame: Baseline and Days 8, 15, 22, 29, 36, and 43
|
Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
|
Baseline and Days 8, 15, 22, 29, 36, and 43
|
Percentage of Responders at Each Visit
Time Frame: Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
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.
|
Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
Mean Platelet Counts of Participants at Each Visit
Time Frame: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
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.
|
Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
Mean Change From Baseline in Platelet Counts at Each Visit
Time Frame: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
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.
|
Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
Mean Maximum Duration for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter
Time Frame: Weeks 1 through 26
|
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.
|
Weeks 1 through 26
|
Mean Total Time for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter
Time Frame: Weeks 1 through 26
|
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.
|
Weeks 1 through 26
|
Percentage of Participants With Bleeding Episode Since the Last Visit
Time Frame: Days 1, 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
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.
|
Days 1, 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
|
Percentage of Participants With a Reduction in Dose and/or Number of Drugs of Concomitant ITP Medications From Baseline
Time Frame: Baseline through Week 26
|
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.
|
Baseline through Week 26
|
Percentage of Participants Who Received Rescue Treatment for ITP
Time Frame: Weeks 1 through 26
|
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.
|
Weeks 1 through 26
|
Mean Number of Days of Concomitant ITP Medication Use Per Month
Time Frame: Weeks 1 through 26
|
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.
|
Weeks 1 through 26
|
Pharmacokinetics of SB-497115-GR, Cmax
Time Frame: Week 9 or 10
|
Cmax: Peak plasma concentration of SB-497115
|
Week 9 or 10
|
Pharmacokinetics of SB-497115-GR, Tmax
Time Frame: Week 9 or 10
|
tmax: Time when Cmax was achieved
|
Week 9 or 10
|
Pharmacokinetics of SB-497115, t1/2
Time Frame: Week 9 or 10
|
t1/2 is half life based on the terminal phase
|
Week 9 or 10
|
Pharmacokinetics of SB-497115-GR, Lambda z
Time Frame: Week 9 or 10
|
Lambda z is first order rate constant associated with the terminal portion of the plasma concentration curve.
|
Week 9 or 10
|
Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24
Time Frame: Week 9 or 10
|
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. |
Week 9 or 10
|
Pharmacokinetics of SB-497115-GR, CL/F
Time Frame: Week 9 or 10
|
CL/F: CL is an estimate of the total body clearance, and F is the fraction of dose absorbed.
|
Week 9 or 10
|
Pharmacokinetics of SB-497115-GR, Vz/F
Time Frame: Week 9 or 10
|
VZ/F: VZ is the volume of distribution based on the terminal phase, and F is the fraction of dose absorbed.
|
Week 9 or 10
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Thrombocytopenia
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura
- Purpura, Thrombocytopenic
- Purpura, Thrombocytopenic, Idiopathic
Other Study ID Numbers
- 108109
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Idiopathic Thrombocytopenic Purpura
-
University Hospital, BordeauxCompletedChronic Idiopathic Thrombocytopenic Purpura | Congenital Thrombocytopenia
-
Jiangsu HengRui Medicine Co., Ltd.UnknownChronic Idiopathic Thrombocytopenic PurpuraChina
-
Eisai Inc.CompletedChronic Idiopathic Thrombocytopenic Purpura | Purpura, Thrombocytopenic, IdiopathicUnited States
-
Bio Products LaboratoryCompletedChronic Idiopathic Thrombocytopenic PurpuraUnited States, India, Argentina
-
Eisai Inc.CompletedPurpura, Thrombocytopenic, Idiopathic | Chronic Thrombocytopenia | Acute Idiopathic Thrombocytopenic PurpuraNetherlands
-
Protalex, Inc.TerminatedPhase I Safety and Tolerability Study of Staphylococcal Protein A in Adult Patients With Chronic ITPIdiopathic Thrombocytopenic Purpura (ITP)Australia, New Zealand
-
CSL LimitedCompletedIdiopathic Thrombocytopenic Purpura (ITP)Australia
-
University Hospital, AngersMinistry of Health, FranceUnknownAcute Idiopathic Thrombocytopenic PurpuraFrance
-
Mahidol UniversityRamathibodi HospitalCompletedChronic Idiopathic Thrombocytopenic Purpura | Helicobacter Pylori InfectionThailand
-
AmgenCompletedThrombocytopenia | Immune Thrombocytopenia | Idiopathic Thrombocytopenic Purpura | Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) | Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) | Thrombocytopenic PurpuraUnited States, Canada, Australia
Clinical Trials on SB-497115-GR 12.5mg
-
Abramson Cancer Center of the University of PennsylvaniaTerminatedAcute Myelogenous Leukemia (AML)United States
-
Weill Medical College of Cornell UniversityNovartisCompletedImmune Thrombocytopenia | Platelet DisorderUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedHematopoietic Cell Transplantation Recipient | Bone Marrow Transplantation Recipient | Cord Blood Transplant RecipientUnited States
-
GlaxoSmithKlineCompletedPurpura, Thrombocytopenic, Idiopathic | Idiopathic Thrombocytopenic PurpuraJapan
-
GlaxoSmithKlineCompletedHepatitis C, ChronicJapan
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedPrimary Myelofibrosis | Thrombocytopenia | Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
Case Comprehensive Cancer CenterActive, not recruitingAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic... and other conditionsUnited States
-
Novartis PharmaceuticalsCompletedPurpura, Thrombocytopaenic, IdiopathicUnited Kingdom, Hong Kong, United States, Germany, Italy, Netherlands, Spain, Taiwan, Thailand, Canada, Denmark, Pakistan, Romania, Slovenia, Russian Federation, Slovakia, Sweden, Poland, China, New Zealand, Ukraine, Australia, Austria and more
-
Novartis PharmaceuticalsCompletedThrombocytopaeniaBelgium, Greece, Netherlands, Romania, China, Korea, Republic of, Tunisia, France, Hong Kong, Ireland, Peru, Poland
-
Dana-Farber Cancer InstituteCompletedMultiple MyelomaUnited States