A Randomized, Parallel, Open-Label Study to Compare the Pharmacokinetics of Ipilimumab (BMS-734016) Process C to Process B in Subjects With Advanced Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 99
- 试验地点
- 7
- 主要终点
- Area Under the Serum Concentration-time Curve (AUC) From Time Zero to Day 21, AUC(0-21d), of Ipilimumab Manufactured by Process C Relative to the AUC(0-21d) of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
研究概览
简要总结
The purpose of this clinical research study is to compare pharmacokinetics of ipilimumab manufactured by two different processes
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
- 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
- •Histologic diagnosis of malignant melanoma
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Measurable/evaluable disease per modified World Health Organization (mWHO) criteria
排除标准
- •Active Brain Metastasis
- •Primary ocular or mucosal melanoma
- •Prior Autoimmune disease
- •Inadequate hematologic, hepatic or renal function
- •Use of immunosuppressants
- •Prior treatment with a CD137 agonist or cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor
研究组 & 干预措施
Ipilimumab (Process B)
Reference
干预措施: Ipilimumab (Biological)
Ipilimumab (Process C)
Test
干预措施: Ipilimumab (Biological)
结局指标
主要结局
Area Under the Serum Concentration-time Curve (AUC) From Time Zero to Day 21, AUC(0-21d), of Ipilimumab Manufactured by Process C Relative to the AUC(0-21d) of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
时间窗: Day 1 to Day 84
The single-dose pharmacokinetic parameters of ipilimumab were derived from serum concentration versus time data. AUC(0-21d) was measured from first dose to end of the induction period as micrograms\*hours per milliliter (μg\*h/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox \[version 2.6.1\]).
Maximum Observed Serum Concentration (Cmax) of Ipilimumab Manufactured by Process C Relative to the Cmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population
时间窗: Day 1 to Day 84
Single-dose Pharmacokinetic (PK) parameters of ipilimumab were derived from serum concentration versus time data. Cmax was measured from first dose to end of the induction period (4 doses) as micrograms per milliliter (μg/mL). Samples were obtained at 0 hour (predose) on Days 1, 2, 3, 4, and Weeks 2, 3, 4, 7, and 10; Day 1, samples were also obtained 1 h 30 minutes (min), 2 h, 2 h 30 min, 3 h 30 min, 4 h 30 min, and 6 h post dose. In calculating PK parameters, predose concentrations and concentrations prior to first quantifiable concentration below the lower limit of quantitation (LLOQ) were treated as "missing" for the calculation of summary statistics. Drug was quantitatively determined in serum by an enzyme-linked immunosorbent assay (ELISA). Individual PK parameter values were derived by non-compartmental methods using a validated PK analysis program (Kinetica™ 4.4.1 within eToolbox \[version 2.6.1\]).
次要结局
- Time of Maximum Observed Serum Concentration (Tmax) of Ipilimumab Manufactured by Process C Relative to the Tmax of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population(Day 1 to Day 84)
- Model Estimates of Mean Absolute Lymphocyte Count at Each Nominal Ipilimumab Induction Dose and at End of the Induction Dosing Period(Day 0 (prior to first dose) to Day 84)
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation(Day 1 to last patient, last visit, approximately 3 years)
- Number of Participants Who Developed Antibodies and Neutralizing Antibodies(Prior to start of drug Week 1 to Week 24 on treatment or end of treatment)
- Clearance (CLT) of Ipilimumab Manufactured by Process C Relative to the CLT of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population(Day 1 to Day 84)
- Volume of Distribution at Steady State (Vss) of Ipilimumab Manufactured by Process C Relative to the Vss of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population(Day 1 to Day 84)
- Best Overall Tumor Response Per Investigator Based on Modified World Health Organization (mWHO) Criteria - All Randomized Participants(Day 1 to last patient, last visit, approximately 3 years)
- Best Overall Tumor Response Per Investigator Based on Immune-related (ir) Response Criteria (RC) - All Randomized Participants(Day 1 to last patient, last visit, approximately 3 years)
- Median Overall Survival Following First Ipilimumab Dose - All Treated Participants(Week 1 (first dose) to last patient, last visit, approximately 3 years)
- Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants up to Data Cutoff(Screening to data cut off for July 2010, approximately 36 Weeks)
- Mean Change From Baseline in Sitting Pulse Rate - All Treated Participants up to Data Cutoff(Screening to data cut off for July 2010, approximately 36 Weeks)
- Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Hematology Laboratory Safety Tests - All Treated Participants(Screening to data cut off for July 2010, approximately 36 Weeks)
- Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Chemistry Laboratory Safety Tests (Non-electrolyte) - All Treated Participants(Screening to data cut off for July 2010, approximately 36 Weeks)
- Number of Participants With 2-Grade or Greater Shift From Baseline (Worsening) in Electrolyte Laboratory Safety Tests - All Treated Participants(Screening to data cut off for July 2010, approximately 36 Weeks)
- Terminal Elimination Half Life (T-HALF) of Ipilimumab Manufactured by Process C Relative to the T-HALF of Ipilimumab Manufactured by Process B - Evaluable Pharmacokinetic Population(Day 1 to Day 84)