A Randomized, Double-blind, Placebo-controlled, Ascending Dose, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Intravenous and Subcutaneous Doses of Recombinant Human C1 Esterase Inhibitor in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
研究概览
简要总结
This trial is looking to gain information about the safety and tolerability of an investigational treatment (SHP623) in healthy adult volunteers. This study will also collect pharmacokinetic data (how the body absorbs and breaks down the study drug).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Must be considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease
- •Male, or non-pregnant, non-lactating female, who agrees to comply with any applicable contraceptive requirements of the protocol, or females of non-child-bearing potential.
- •Body mass index between 18.0 and 30.0 kg/m2 inclusive with a body weight >50 kg (110 lbs.). This inclusion criterion will be assessed only at the first screening visit.
- •Hemoglobin ≥12.0g/ld.
排除标准
- •Have a history of allergic reaction to C1 INH products (e.g. C1 Inhibitor [Human], Berinert [C1 Estrace Inhibitor (Human)] and C1 estrace [recombinant]
- •Known history of alcohol or other substance abuse within the last year.
- •Donation of blood or blood products within 60 days prior to receiving investigational product.
- •Current use of any medication except hormonal replacement therapy, hormonal contraceptives and occasional use of any over-the-counter non-steroidal anti-inflammatory drug (NSAID) or acetaminophen.
- •Have a history of hypercoagulability or other predisposition to thrombotic events.
研究组 & 干预措施
Treatment 1- 4
Treatment A: 9 Subjects will receive dose level I of SHP623 intravenously (IV). B: 9 Subjects will receive dose level I of SHP623 subcutaneously(SC).
干预措施: Recombinant human C1 esterase inhibitor (Drug)
Treatment 1- 4
Treatment A: 9 Subjects will receive dose level I of SHP623 intravenously (IV). B: 9 Subjects will receive dose level I of SHP623 subcutaneously(SC).
干预措施: SHP623 (Drug)
Placebo
3 Subjects will receive placebo for each cohort
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
时间窗: From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE was considered to be a TEAE in a specific treatment period of the study if the date and time of onset were after investigational product administration in that period and if it occurred less than equals to (\<=) Day 28 and was both not present at the start of that period and was not a chronic condition that was part of the participant's medical history, or it was present at the start of that period or as part of the participant's medical history but the severity or frequency increased during that period \<= Day 28. An SAE was defined as any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of SHP623 Occurring at Time of Maximum Observed Concentration During a Dosing Interval (Tmax)(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Time of Maximum Plasma Concentration (Tmax) of SHP623 Sampled During a Dosing Interval(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Terminal Half-life (t1/2) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC 0-inf) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Area Under the Plasma Concentration Curve From Time Zero to 168 Hours Postdose (AUC 0-168) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Total Body Clearance (CL) for Intravascular (IV) Administration of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Total Body Clearance for Extravascular Administration (CL/F) of SHP623 for Subcutaneous (SC) Administration(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Volume of Distribution Associated With the Terminal Slope (Vz) Following Intravenous (IV) Administration of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Volume of Distribution Influenced by Fraction of Dose Absorbed (Vz/F) Following Extravascular Administration of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)