Chronic Idiopathic Thrombocytopenic Purpura, Purpura, Thrombocytopenic, Idiopathic
Conditions
Keywords
thrombopoietin,, immunosuppressive therapy,, eltrombopag,, idiopathic thrombocytopenic purpura,, blood platelet,, splenectomy
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
Interventions
DRUGSB-497115-GR 12.5mg
SB-497115-GR 12.5mg tablet once a day
DRUGSB-497115-GR 25mg
SB-497115-GR 25mg tablet once a day
DRUGSB-497115-GR 12.5mg matching placebo
SB-497115-GR 12.5mg matching placebo x1 or 2 tablet once a day
DRUGSB-497115-GR 50 mg
SB-497115-GR 25mg tablet x2 once a day
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders at Week 6 | 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). |
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Platelet Count at Each Visit | Baseline and Days 8, 15, 22, 29, 36, and 43 | Blood taken from peripheral blood vessels was used for the measurement of platelet counts. |
| Mean Change From Baseline in Platelet Counts at Each Visit | 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 |
| Percentage of Participants With Bleeding Episodes Since the Last Visit | 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). |
| Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline and Days 8, 15, 22, 29, 36, and 43 | Blood taken from peripheral blood vessels was used for the measurement of platelet counts. |
| Mean Platelet Counts of Participants at Each Visit | 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. |
| Mean Maximum Duration for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter | 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. |
| Mean Total Time for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter | 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. |
| Percentage of Participants With Bleeding Episode Since the Last Visit | 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. |
| Percentage of Participants With a Reduction in Dose and/or Number of Drugs of Concomitant ITP Medications From Baseline | 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. |
| Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6 | 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. |
| Mean Number of Days of Concomitant ITP Medication Use Per Month | 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. |
| Pharmacokinetics of SB-497115-GR, Cmax | Week 9 or 10 | Cmax: Peak plasma concentration of SB-497115 |
| Pharmacokinetics of SB-497115-GR, Tmax | Week 9 or 10 | tmax: Time when Cmax was achieved |
| Pharmacokinetics of SB-497115, t1/2 | Week 9 or 10 | t1/2 is half life based on the terminal phase |
| Pharmacokinetics of SB-497115-GR, Lambda z | Week 9 or 10 | Lambda z is first order rate constant associated with the terminal portion of the plasma concentration curve. |
| Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | 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. |
| Pharmacokinetics of SB-497115-GR, CL/F | Week 9 or 10 | CL/F: CL is an estimate of the total body clearance, and F is the fraction of dose absorbed. |
| Pharmacokinetics of SB-497115-GR, Vz/F | 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. |
| Percentage of Participants Who Received Rescue Treatment for ITP | 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. |
| Percentage of Responders at Each Visit | 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). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB-497115-GR SB-497115-GR 12.5 mg for the first 3 weeks of the double-blind phase. The dose of study medication was adjusted at Week 3 based on the participant's platelet count and then continued up to Week 7. | 15 |
| Placebo Placebo 12.5 mg for the first 3 weeks of the double-blind phase. The dose of placebo was adjusted at Week 3 based on the participant's platelet count and then continued up to Week 7. | 8 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Treatment Period | Adverse Event | 0 | 1 | 0 |
| Open-Label Treatment Period | Lack of Efficacy | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | SB-497115-GR | Placebo | Total |
|---|---|---|---|
| Age Continuous | 53.7 years STANDARD_DEVIATION 13.72 | 58.4 years STANDARD_DEVIATION 11.72 | 55.3 years STANDARD_DEVIATION 12.98 |
| Race/Ethnicity, Customized Japanese Heritage | 15 participants | 8 participants | 23 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 1 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 8 | 7 / 15 | 19 / 23 |
| serious Total, serious adverse events | 0 / 8 | 1 / 15 | 6 / 23 |
Outcome results
Primary
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).
Time frame: Week 6
Population: Full Analysis Set: all randomized participants, with the exception of (1) those who did not receive any dose of study medication and (2) those with no valid platelet count measurements on therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Number of Responders at Week 6 | Responders | 9 Participants |
| SB-497115-GR | Number of Responders at Week 6 | Non-responders | 6 Participants |
| Placebo | Number of Responders at Week 6 | Responders | 0 Participants |
| Placebo | Number of Responders at Week 6 | Non-responders | 8 Participants |
95% CI: [35.21, 84.79]
Primary
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.
Time frame: Week 26
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB-497115-GR | 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 | 43.5 percentage of participants |
95% CI: [23.19, 65.51]
Secondary
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
Time frame: Baseline and Days 8, 15, 22, 29, 36, and 43
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 36 | -0.8 10^9/Liter | Standard Deviation 7.94 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 8 | 1.6 10^9/Liter | Standard Deviation 6.05 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 29 | -2.0 10^9/Liter | Standard Deviation 4.17 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 15 | 0.9 10^9/Liter | Standard Deviation 5.46 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 43 | -2.8 10^9/Liter | Standard Deviation 9.41 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 22 | -1.0 10^9/Liter | Standard Deviation 3.02 |
| Placebo | Mean Change From Baseline in Platelet Counts at Each Visit | Day 22 | 35.0 10^9/Liter | Standard Deviation 46.52 |
| Placebo | Mean Change From Baseline in Platelet Counts at Each Visit | Day 29 | 53.9 10^9/Liter | Standard Deviation 46.02 |
| Placebo | Mean Change From Baseline in Platelet Counts at Each Visit | Day 36 | 80.1 10^9/Liter | Standard Deviation 77.06 |
| Placebo | Mean Change From Baseline in Platelet Counts at Each Visit | Day 43 | 75.8 10^9/Liter | Standard Deviation 99.93 |
| Placebo | Mean Change From Baseline in Platelet Counts at Each Visit | Day 8 | 7.6 10^9/Liter | Standard Deviation 16.47 |
| Placebo | Mean Change From Baseline in Platelet Counts at Each Visit | Day 15 | 35.5 10^9/Liter | Standard Deviation 56.11 |
Secondary
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.
Time frame: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Week 22 | 61.1 10^9/Liter | Standard Deviation 54.85 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 8 | 6.4 10^9/Liter | Standard Deviation 13.53 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 15 | 25.1 10^9/Liter | Standard Deviation 46.73 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 22 | 24.6 10^9/Liter | Standard Deviation 39.37 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 29 | 38.9 10^9/Liter | Standard Deviation 42.37 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 36 | 61.7 10^9/Liter | Standard Deviation 69.53 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Day 43 | 61.6 10^9/Liter | Standard Deviation 86.72 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Week 10 | 71.4 10^9/Liter | Standard Deviation 80.01 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Week 14 | 104.5 10^9/Liter | Standard Deviation 120.2 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Week 18 | 69.4 10^9/Liter | Standard Deviation 80.23 |
| SB-497115-GR | Mean Change From Baseline in Platelet Counts at Each Visit | Week 26 | 68.4 10^9/Liter | Standard Deviation 46.49 |
Secondary
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.
Time frame: Weeks 1 through 26
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Mean Maximum Duration for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter | 59.5 Days | Standard Deviation 46.99 |
Secondary
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.
Time frame: Weeks 1 through 26
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Mean Number of Days of Concomitant ITP Medication Use Per Month | 25.14 Days | Standard Deviation 11.796 |
Secondary
Mean Platelet Count at Each Visit
Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
Time frame: Baseline and Days 8, 15, 22, 29, 36, and 43
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SB-497115-GR | Mean Platelet Count at Each Visit | Baseline | 19.3 10^9/Liter | Standard Deviation 6.79 |
| SB-497115-GR | Mean Platelet Count at Each Visit | Day 15 | 54.9 10^9/Liter | Standard Deviation 55.84 |
| SB-497115-GR | Mean Platelet Count at Each Visit | Day 29 | 73.3 10^9/Liter | Standard Deviation 46.72 |
| SB-497115-GR | Mean Platelet Count at Each Visit | Day 22 | 54.4 10^9/Liter | Standard Deviation 46.88 |
| SB-497115-GR | Mean Platelet Count at Each Visit | Day 8 | 26.9 10^9/Liter | Standard Deviation 17.77 |
| SB-497115-GR | Mean Platelet Count at Each Visit | Day 36 | 99.4 10^9/Liter | Standard Deviation 78.62 |
| SB-497115-GR | Mean Platelet Count at Each Visit | Day 43 | 95.1 10^9/Liter | Standard Deviation 100.25 |
| Placebo | Mean Platelet Count at Each Visit | Day 36 | 11.9 10^9/Liter | Standard Deviation 10.79 |
| Placebo | Mean Platelet Count at Each Visit | Day 8 | 14.3 10^9/Liter | Standard Deviation 12.26 |
| Placebo | Mean Platelet Count at Each Visit | Day 29 | 10.6 10^9/Liter | Standard Deviation 9.04 |
| Placebo | Mean Platelet Count at Each Visit | Day 43 | 9.9 10^9/Liter | Standard Deviation 4.76 |
| Placebo | Mean Platelet Count at Each Visit | Day 15 | 13.5 10^9/Liter | Standard Deviation 12.15 |
| Placebo | Mean Platelet Count at Each Visit | Day 22 | 11.6 10^9/Liter | Standard Deviation 9.5 |
| Placebo | Mean Platelet Count at Each Visit | Baseline | 12.6 10^9/Liter | Standard Deviation 8.65 |
Secondary
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.
Time frame: Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Baseline | 16.5 10^9/Liter | Standard Deviation 8.45 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Day 8 | 23.0 10^9/Liter | Standard Deviation 16.77 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Day 15 | 41.5 10^9/Liter | Standard Deviation 48.32 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Day 22 | 41.0 10^9/Liter | Standard Deviation 41.8 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Day 29 | 55.3 10^9/Liter | Standard Deviation 45.75 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Day 36 | 78.1 10^9/Liter | Standard Deviation 72.76 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Week 10 | 88.9 10^9/Liter | Standard Deviation 81.15 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Week 14 | 121.6 10^9/Liter | Standard Deviation 121.2 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Week 18 | 87.3 10^9/Liter | Standard Deviation 80.09 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Week 22 | 78.5 10^9/Liter | Standard Deviation 57.58 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Week 26 | 86.2 10^9/Liter | Standard Deviation 49.62 |
| SB-497115-GR | Mean Platelet Counts of Participants at Each Visit | Day 43 | 78.0 10^9/Liter | Standard Deviation 88.31 |
Secondary
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.
Time frame: Weeks 1 through 26
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Mean Total Time for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter | 78.4 Days | Standard Deviation 54.56 |
Secondary
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.
Time frame: Weeks 2 through 6
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6 | Responders | 5 Participants |
| SB-497115-GR | Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6 | Non-responders | 9 Participants |
| Placebo | Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6 | Responders | 0 Participants |
| Placebo | Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6 | Non-responders | 8 Participants |
Secondary
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.
Time frame: Baseline and Days 8, 15, 22, 29, 36, and 43
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >15 to <30 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC =>50 to <=200 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >200 to <=400 x 10^9/L | 1 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC <=15 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >15 to <30 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >=30 to <=50 x 10^9/L | 5 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >=30 to <=50 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC =>50 to <=200 x 10^9/L | 5 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >200 to <=400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC <=15 x 10^9/L | 2 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC <=15 x 10^9/L | 1 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >15 to <30 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >15 to <30 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >=30 to <=50 x 10^9/L | 4 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC =>50 to <=200 x 10^9/L | 9 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >=30 to <=50 x 10^9/L | 2 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >200 to <=400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC =>50 to <=200 x 10^9/L | 9 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >15 to <30 x 10^9/L | 2 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >200 to <=400 x 10^9/L | 1 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC <=15 x 10^9/L | 2 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >=30 to <=50 x 10^9/L | 1 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >200 to <=400 x 10^9/L | 2 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC =>50 to <=200 x 10^9/L | 7 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, Platelet counts (PC) <=15 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >15 to <30 x 10^9/L | 12 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >15 to <30 x 10^9/L | 6 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >=30 to <=50 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC =>50 to <=200 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >200 to <=400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >=30 to <=50 x 10^9/L | 5 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC =>50 to <=200 x 10^9/L | 1 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >400 x 10^9/L | 0 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC <=15 x 10^9/L | 3 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC <=15 x 10^9/L | 2 Participants |
| SB-497115-GR | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >15 to <30 x 10^9/L | 2 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC <=15 x 10^9/L | 7 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >15 to <30 x 10^9/L | 1 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC <=15 x 10^9/L | 5 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC <=15 x 10^9/L | 6 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC <=15 x 10^9/L | 5 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 15, PC >=30 to <=50 x 10^9/L | 1 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >15 to <30 x 10^9/L | 3 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >=30 to <=50 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >=30 to <=50 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >15 to <30 x 10^9/L | 1 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC <=15 x 10^9/L | 7 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >200 to <=400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 22, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >=30 to <=50 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC <=15 x 10^9/L | 6 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >15 to <30 x 10^9/L | 2 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >15 to <30 x 10^9/L | 2 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 43, PC >400 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC >=30 to <=50 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 8, PC >=30 to <=50 x 10^9/L | 1 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 29, PC =>50 to <=200 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >15 to <30 x 10^9/L | 0 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Baseline, Platelet counts (PC) <=15 x 10^9/L | 6 Participants |
| Placebo | Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category | Day 36, PC >=30 to <=50 x 10^9/L | 1 Participants |
Secondary
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.
Time frame: Weeks 1 through 26
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB-497115-GR | Percentage of Participants Who Received Rescue Treatment for ITP | 9 Percentage of participants |
Secondary
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.
Time frame: Baseline through Week 26
Population: Full Analysis Set. Four participants in the Full Analysis Set did not have concomitant ITP medication at Baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB-497115-GR | Percentage of Participants With a Reduction in Dose and/or Number of Drugs of Concomitant ITP Medications From Baseline | 36.8 Percentage of participants |
Secondary
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.
Time frame: Days 1, 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 1 | 48 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 8 | 35 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 15 | 27 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 22 | 36 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 29 | 18 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 36 | 23 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Day 43 | 27 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Week 10 | 11 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Week 14 | 14 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Week 18 | 26 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Week 22 | 28 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episode Since the Last Visit | Week 26 | 5 Percentage of participants |
Secondary
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).
Time frame: Days 1, 8, 15, 22, 29, 36, and 43
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 8 | 13 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 22 | 29 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 36 | 7 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 29 | 0 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 15 | 14 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 43 | 14 Percentage of participants |
| SB-497115-GR | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 1 | 33 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 43 | 75 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 29 | 38 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 1 | 75 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 8 | 63 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 15 | 63 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 22 | 75 Percentage of participants |
| Placebo | Percentage of Participants With Bleeding Episodes Since the Last Visit | Day 36 | 63 Percentage of participants |
Secondary
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).
Time frame: Days 8, 15, 22, 29, 36, and 43
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Percentage of Responders at Each Visit | Day 8 | 6.7 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 15 | 26.7 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 22 | 33.3 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 29 | 60.0 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 36 | 66.7 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 43 | 60.0 Percentage of responders |
| Placebo | Percentage of Responders at Each Visit | Day 36 | 0 Percentage of responders |
| Placebo | Percentage of Responders at Each Visit | Day 8 | 0 Percentage of responders |
| Placebo | Percentage of Responders at Each Visit | Day 29 | 0 Percentage of responders |
| Placebo | Percentage of Responders at Each Visit | Day 15 | 0 Percentage of responders |
| Placebo | Percentage of Responders at Each Visit | Day 22 | 0 Percentage of responders |
| Placebo | Percentage of Responders at Each Visit | Day 43 | 0 Percentage of responders |
Secondary
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.
Time frame: Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SB-497115-GR | Percentage of Responders at Each Visit | Day 15 | 17.4 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 22 | 21.7 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 8 | 4.3 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 36 | 56.5 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 29 | 47.8 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Week 10 | 57.1 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Week 18 | 50.0 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Week 22 | 52.4 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Week 14 | 60.9 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Day 43 | 52.2 Percentage of responders |
| SB-497115-GR | Percentage of Responders at Each Visit | Week 26 | 69.6 Percentage of responders |
Secondary
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.
Time frame: Week 9 or 10
Population: PK Population. Data from one participant were abnormal; this participant was excluded from this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | AUClast | 41671.5 hr*ng/mL | Standard Deviation 24344.64 |
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | AUC0-24 | 41637.2 hr*ng/mL | Standard Deviation 24361.51 |
| Placebo | Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | AUClast | 92556.2 hr*ng/mL | Standard Deviation 41095.63 |
| Placebo | Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | AUC0-24 | 92527.5 hr*ng/mL | Standard Deviation 41122.3 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | AUC0-24 | 171551.0 hr*ng/mL | Standard Deviation 75242.59 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24 | AUClast | 171523.2 hr*ng/mL | Standard Deviation 75250.93 |
Secondary
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.
Time frame: Week 9 or 10
Population: PK Population. Data from one participant were abnormal; this participant was excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, CL/F | 0.37156 L/hr (Liters/hour) | Standard Deviation 0.154284 |
| Placebo | Pharmacokinetics of SB-497115-GR, CL/F | 0.30923 L/hr (Liters/hour) | Standard Deviation 0.114096 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, CL/F | 0.33035 L/hr (Liters/hour) | Standard Deviation 0.124401 |
Secondary
Pharmacokinetics of SB-497115-GR, Cmax
Cmax: Peak plasma concentration of SB-497115
Time frame: Week 9 or 10
Population: Pharmacokinetic (PK) Population: all participants with valid PK data following SB-497115-GR treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, Cmax | 2992.4 ng/mL (nanograms/milliliter) | Standard Deviation 1253.14 |
| Placebo | Pharmacokinetics of SB-497115-GR, Cmax | 6776.4 ng/mL (nanograms/milliliter) | Standard Deviation 2619.62 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, Cmax | 11877.8 ng/mL (nanograms/milliliter) | Standard Deviation 3926.21 |
Secondary
Pharmacokinetics of SB-497115-GR, Lambda z
Lambda z is first order rate constant associated with the terminal portion of the plasma concentration curve.
Time frame: Week 9 or 10
Population: PK Population. Data from one participant were abnormal; this participant was excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, Lambda z | 0.04021 1/hour | Standard Deviation 0.015558 |
| Placebo | Pharmacokinetics of SB-497115-GR, Lambda z | 0.02724 1/hour | Standard Deviation 0.006881 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, Lambda z | 0.04040 1/hour | Standard Deviation 0.011422 |
Secondary
Pharmacokinetics of SB-497115-GR, Tmax
tmax: Time when Cmax was achieved
Time frame: Week 9 or 10
Population: PK Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, Tmax | 3.192 Hours |
| Placebo | Pharmacokinetics of SB-497115-GR, Tmax | 4.000 Hours |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, Tmax | 2.967 Hours |
Secondary
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.
Time frame: Week 9 or 10
Population: PK Population. Data from one participant were abnormal; this participant was excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115-GR, Vz/F | 5.6267 Liters | Standard Deviation 2.00964 |
| Placebo | Pharmacokinetics of SB-497115-GR, Vz/F | 5.3870 Liters | Standard Deviation 1.75077 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115-GR, Vz/F | 5.0391 Liters | Standard Deviation 1.76091 |
Secondary
Pharmacokinetics of SB-497115, t1/2
t1/2 is half life based on the terminal phase
Time frame: Week 9 or 10
Population: PK Population. Data from one participant were abnormal; this participant was excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SB-497115-GR | Pharmacokinetics of SB-497115, t1/2 | 19.50 Hours | Standard Deviation 7.164 |
| Placebo | Pharmacokinetics of SB-497115, t1/2 | 29.96 Hours | Standard Deviation 7.664 |
| SB-497115-GR 50 mg | Pharmacokinetics of SB-497115, t1/2 | 18.19 Hours | Standard Deviation 4.938 |