An Open-Label, Single-Dose, Phase 1/2 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Human Protein C (TAK-662) for the Treatment of Congenital Protein C Deficiency in Japanese Subjects Followed by an Extension Part
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 4
- 主要终点
- PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662
研究概览
简要总结
Pharmacokinetic Part:
This study is for Japanese participants with congenital protein C deficiency. The main aim of this study is to check how much TAK-662 stays in their blood over time. This will help the study sponsor (Takeda) to work out the best dose to give patients in the future.
Participants will receive 1 single infusion of TAK-662.
They will stay at the clinic until 3 days after the infusion. Then, participants will return to their clinic 7 days after the infusion to check side effects from the study treatment.
Extension Part:
Participants who will complete the PK part will be given an opportunity to continue TAK-662 administration as 3 different treatment options (on-demand therapy, short-term prophylaxis, and long-term prophylaxis) in the Extension part, until the commercial protein C concentrate is available at each study site or study termination.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants with Japanese nationality.
- •A diagnosis of congenital protein C deficiency (homozygous or compound heterozygous).
- •Asymptomatic participant.
- •Oral anticoagulants allowed to be received.
- •Extension part:
- •Participants who participated in the PK part of this study (TAK-662-1501).
- •Participant who are; a. Diagnosed with PF, CISN/WISN, and/or other acute thromboembolic episode for on-demand treatment only; b. Requiring treatment with TAK-662 for short-term prophylaxis for surgical procedures; c. Requiring treatment with TAK-662 for long-term prophylaxis.
排除标准
- •Current or recurrent disease that could affect the action, or disposition of the investigational product (IP), or clinical or laboratory assessments.
- •A body weight less than 8 kg.
- •Serious liver dysfunction, judged by the investigator.
- •Any thrombosis within 2 weeks prior to administration of the IP.
- •Other investigational product than TAK-662 received within 60 days prior to the administration of the IP.
- •Current or relevant history of physical or psychiatric illness, or any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the IP or procedures.
- •Current use of any medication (including over-the-counter, herbal, or homeopathic preparations) that could affect (improve or worsen) the condition being studied, or could affect the action or disposition of the IP, or clinical or laboratory assessment.
- •Known or suspected intolerance or hypersensitivity to the IP, closely-related compounds, or any of the stated ingredients.
- •Known history of alcohol or other substance abuse within the last year.
- •Within 30 days prior to the first dose of IP, a participant has been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this sponsored study.
- •Extension Part:
- •New serious medical conditions which could affect participant's safety or treatment were observed during participation in the PK part of this study (TAK-662-1501).
研究组 & 干预措施
TAK-662 80 IU/kg
TAK-662 80 international unit (IU)/kg, single intravenous infusion over 15 minutes on Day 1. In the extension part, dose of TAK-662 will be modified per participants. TAK-662 is Protein C Concentrate, which is a lyophilized, sterile concentrate of human protein C.
干预措施: TAK-662 (Drug)
结局指标
主要结局
PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
t1/2 of TAK-662 was reported.
PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
Tmax of TAK-662 was reported.
PK Part: Protein C Activity Level of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
Protein C is a vitamin K-dependent plasma protein and is an important component of the coagulation system. Protein C activity level was measured by chromogenic assays. Protein C activity level of TAK-662 was reported.
PK Part: Incremental Recovery (IR) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
IR of TAK-662 was reported measured in terms of international unit per milliliter/ international unit per kilogram (IU/mL)/(IU/kg).
PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
IVR corrected for plasma was determined using the formula: IVR (percentage \[%\])= (Maximum observed plasma concentration (Cmax) \[IU/mL\] - Concentration (C) pre-infusion \[IU/mL\]) \* Plasma volume pre-infusion (PV) milliliter (mL)/ Dose (international unit \[IU\])\*100 where Cmax was the observed Cmax value before baseline correction. IVR of TAK-662 measured in terms of percentage was reported.
PK Part: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
AUClast of TAK-662 was reported measured in terms of international unit\*hour per milliliter (IU\*h/ml).
PK Part: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
AUC0-infinity of TAK-662 was reported.
PK Part: Maximum Observed Plasma Concentration (Cmax) of TAK-662
时间窗: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
Cmax of TAK-662 was reported.
次要结局
- PK and Extension Parts: Number of Participants With Treatment-Related Adverse Experiences (AEs)(PK Part: From the start of study drug administration up to Day 7; Extension Part: From the first dose of study drug administration in the Extension Part up to 35 months)
- Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment(Extension Part: From the first dose of TAK-662 on-demand treatment in the Extension Part up to 35 months)
- Extension Part: Percentage of Surgical Episodes During Short-Term Prophylaxis That is Free of Presentations of PF or Thromboembolic Complications(Extension Part: From the first dose of TAK-662 short-term prophylaxis treatment in the Extension Part up to 35 months)
- Extension Part: Number of Episodes of PF and/or Thrombotic Episodes During Long-Term Prophylaxis(Extension Part: From the first dose of TAK-662 long-term prophylaxis treatment in the Extension Part up to 35 months)