| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Immune thrombocytopenic purpura (ITP) | |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To determine the efficacy of SB-497115-GR as a thrombopoietic agent, when administered once daily for 6 weeks to previously treated adult subjects with chronic ITP. | |
| E.2.2 | Secondary objectives of the trial | •To assess the safety and tolerability of SB-497115-GR when administered once daily for 6 weeks to previously treated adult subjects with chronic ITP.
•To characterize the population pharmacokinetic profile of oral SB-497115-GR using a combined sparse and serial pharmacokinetic sampling strategy when administered once daily for 6 weeks to previously treated adult subjects with chronic ITP.
•To determine the pharmacodynamic effect of SB-497115-GR on markers of thrombopoiesis when administered once daily for 6 weeks to previously treated adult subjects with chronic ITP.
•To assess the impact of SB-497115-GR on the incidence and severity of symptoms of thrombocytopenia when administered once daily for 6 weeks to previously treated adult subjects with chronic ITP.
•To assess the impact of SB-497115-GR on the quality of life when administered once daily for 6 weeks to previously treated adult subjects with chronic ITP.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1.Diagnosed with chronic ITP for at least 6 months prior to screening, and have a platelet count of < 30,000 platelets/L on Day 1 (or within 24 hours prior to dosing on Day 1).
2.Previously treated patients who have either not responded to one or more prior therapies, or who have relapsed within 3 months of prior therapy. Previous treatments for chronic ITP include corticosteroids, immunoglobulins (IVIG and anti-D immunoglobulin), azathioprine, danazol, cyclophosphamide, immunomodulators and/or splenectomy. Previous therapy for ITP with immunoglobulins, immunomodulators and cyclophosphamide must have been completed at least 2 weeks prior to randomization (See Inclusion Criterion 3).
3.Subjects treated with maintenance immunosuppressive therapy (corticosteroids, azathioprine, danazol, cyclosporin A, mycophenolate mofetil) must be receiving a dose that has been stable for at least 1 month.
4.Normal prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT), no history of clotting disorder, other than ITP.
5.A complete blood count (CBC), reticulocyte count, creatinine, ALT, AST, bilirubin and/or alkaline phosphatase within the reference range, with the following exceptions:
•platelet count < 30,000/L is required for inclusion,
•Hemoglobin: females and males 10.0 g/dL are eligible for inclusion,
•ANC 1500/L (1.5 x 109/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
6.Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oopherectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
•Complete abstinence from intercourse;
•Intrauterine device (IUD);
•Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);
•Male partner is sterile prior to entry into the study and is the only partner of the female;
•Systemic contraceptives (combined or progesterone only).
7.Subject is 18 years old.
8.Subject has signed and dated written informed consent.
9.Subject is able to understand and comply with protocol requirements and instructions and intends to complete the study as planned.
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| E.4 | Principal exclusion criteria | 1.Any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the Investigator, makes the subject unsuitable for participation in the study.
2.History of thrombosis within the last year.
3.Pre-existing cardiac disease (including congestive heart failure, and arrhythmia requiring treatment); myocardial infarction in the last 3 months; or clinically significant findings on resting 12-lead ECG at screening.
4.Female subjects who are nursing or pregnant (positive serum or urine -human chorionic gonadotrophin pregnancy test) at screening or pre-dose on Day 1.
5.History of alcohol/drug abuse or dependence within 12 months of the study.
6.Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
7.Subject has consumed aspirin, aspirin-containing compounds, salicylates, anti-coagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for > 3 consecutive days within 2 weeks of the study start and until the end of the study.
8.Subject has consumed liquid antacids (e.g. Maalox™, Mylanta™, Amphogel™, milk of magnesia), chewable antacids (e.g. TUMS™) or calcium supplements within 48 hours of the first dose of study medication, and/or will require these medications during the 6-week dosing period.
9.Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements (See Exclusion 7 for calcium supplements), within 1 week of the study start. Subject has consumed rosuvastatin or pravastatin within 1 week of the first dose of study medication and/or will require these medications during the 6-week dosing period.
10.History of platelet aggregation that prevents reliable measurement of platelet counts.
11.Any laboratory or clinical evidence for HIV infection; any clinical history or laboratory evidence for hepatitis C infection; any clinical history or laboratory evidence for chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. If a potential subject has no clinical history that would support HIV infection or hepatitis infection, no further laboratory screening is necessary; however, standard medical practice would suggest further evaluation of patients who have risk factors for these infections.
12.Previous participation in a clinical study with SB-497115-GR. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Proportion of subjects with a platelet count of 50,000/L after 42 days of dosing (compared to baseline count of < 30,000/L). Subjects who meet this criterion will be referred to as treatment responders. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
