An Open-label Safety Study of S-888711 in Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The primary objective of this study was to assess the long-term safety of lusutrombopag in the treatment of adults with relapsed persistent or chronic ITP with or without prior splenectomy.
详细描述
This was an open-label, long-term safety study of lusutrombopag in the treatment of adults with relapsed persistent or chronic ITP with or without prior splenectomy. Patients who participate in this study must have completed the Phase 2 study 0913M0621 (NCT01054443), a double-blind, placebo controlled, parallel group study that evaluated the efficacy and safety lusutrombopag during which they either completed treatment or discontinued treatment due to a platelet count > 400,000/μL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who previously participated in Study 0913M0621 (NCT01054443) and who completed treatment or discontinued treatment due to a platelet count > 400,000/μL and continued to meet all inclusion criteria of the previous study, listed below, including platelet counts < 50,000/μL were eligible for study participation. For the purpose of this study, initial screening visit and all prestudy time period refer to Study 0913M
- •A signed and dated written informed consent
- •Males and females ≥ 18 years of age
- •All subjects must agree to use barrier contraception
- •Diagnosis of ITP
- •Subjects > 60 years must have had a diagnostic bone marrow aspiration
- •Relapsed persistent or chronic ITP status, with or without prior splenectomy
- •Subjects receiving steroid therapy must be on a stable dose for at least 2 weeks prior to Screening
- •Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN) at Screening
- •Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed
排除标准
- •History of clinically important hemorrhagic clotting disorder
- •Females who are pregnant, lactating, or taking oral contraceptives
- •History of alcohol/drug abuse or dependence within 1 year
- •Use of the following drugs or treatment prior to Visit 1 (Day 1):
- •Within 1 week - Rho(D) immune globulin or intravenous immunoglobulin;
- •Within 2 weeks - plasmaphoresis treatment;
- •Within 4 weeks - use of anti-platelet or anti-coagulant drugs;
- •Within 8 weeks - rituximab;
- •Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy;
- •History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Initial Screening
- •Splenectomy within 4 weeks prior to Initial Screening
- •Clinically significant laboratory abnormalities
- •Hemoglobin < 10.0 g/dL for men or women, not clearly related to ITP
- •Absolute neutrophil count < 1000/mm3
- •Abnormal peripheral blood smear with evidence of fibrosis confirmed by bonemarrow biopsy
- •Total bilirubin > 1.5 x upper limit of normal
- •Alanine aminotransferase (ALT) > 1.5 x upper limit of normal
- •Aspartate aminotransferase (AST) > 1.5 x upper limit of normal
- •Creatinine > 1.5 x upper limit of normal
- •Human immunodeficiency virus positive
- •Hepatitis A IgM antibody positive, hepatitis B surface antigen or hepatitis C antibody positive
- •Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Initial Screening
- •Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665)
- •Exposure to an investigative medication within 4 weeks prior to the initial Screening Visit
研究组 & 干预措施
Lusutrombopag
Participants received lusutrombopag 0.5 mg administered orally once a day for up to 3 years or until study termination. The dose was adjusted based on platelet counts. If a subject's platelet count remained < 50,000/μL, the dose could have been increased by 0.25 mg up to a maximum dose of 2.0 mg.
干预措施: Lusutrombopag (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: From first dose of study drug in the extension study up to 6 weeks after last dose; median (range) time on study treatment was 148 (10-387) days.
An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug.
次要结局
- Percentage of Participants Who Achieved a Platelet Count of < 50,000 Cells/μL, Between 50,000 to 400,000 Cells/μL, and ≥ 400,000 Cells/μL(Platelets were assessed at Weeks 1, 2, 3, 4, 5, and 6, Months 1, 2, 3, 6, 9, and 12, and every 3 months thereafter, until end of treatment; median (range) time on treatment was 148 (10-387) days.)
- Change From Baseline in Platelet Counts at the Final Visit(Baseline and the final visit (If a subject had multiple platelet count measurements for the specific dose level due to dose adjustments, the final platelet count was used))
- Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period(Bleeding assessments were performed at Weeks 1, 2, 3, 4, 5, and 6, Months 1, 2, 3, 6, 9, and 12, and every 3 months thereafter until end of treatment; median (range) time on treatment was 148 (10-387) days.)
- Duration of Response(From first dose of study drug in the extension study up to 6 weeks after last dose; median (range) time on treatment was 148 (10 - 387) days.)
- Percentage of Participants Who Achieved a Platelet Count of < 50,000 Cells/μL, Between 50,000 to 400,000 Cells/μL, and ≥ 400,000 Cells/μL Without Rescue Medication(Platelets were assessed at Weeks 1, 2, 3, 4, 5, and 6, Months 1, 2, 3, 6, 9, and 12, and every 3 months thereafter, until end of treatment; median (range) time on treatment was 148 (10-387) days.)