Comparative Pharmacokinetic Profile of Interferon Beta-1a (Bioferon®) Administered as Single i.v. Doses in HSA-free Formulation and HSA+ Solution and as Multiple s.c. Doses in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Composite of interferon beta-1a PK parameters
研究概览
简要总结
Phase I study aiming at:
- establishing the pharmacokinetic profile of interferon beta-1a after i.v. administration of the formulation BioPartners IFN beta-1a without albumin (HSA-free solution in pre-filled syringes) at 18 MIU;
- investigating the possible impact of albumin on pharmacokinetic profile by comparing 3 different i.v. formulations: BioPartners IFN beta-1a without albumin (HSA-free solution in pre-filled syringes), BioPartners IFN beta-1a with added albumin (HSA+), and Rebif® from Merck-Serono, a registered IFN beta-1a solution containing HSA;
- establishing the steady state pharmacokinetic profile of BioPartners IFN beta-1a in HSA-free solution after 4 subsequent s.c. doses of 18 MIU given at 48 hour intervals against Rebif® using the same regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects aged between 18 and 45 years
- •Weight range between 55 and 95 kg for males, 45 and 80 kg for females, providing body mass index (BMI) was between 18 and 29 kg/m2
- •Absence of significant findings in the medical history and physical examination
- •Absence of significant laboratory abnormalities as judged by the investigator.
- •12-lead ECG without significant abnormalities
- •Negative urine drug screen
排除标准
- •History of major renal, hepatic, immunological, haematological, gastrointestinal, genitourinary, neurological, or rheumatological disorders
- •Active diseases of any type, even if mild, including inflammatory disorders and infections.
- •Pregnant or lactating women or women contemplating becoming pregnant during study. Female subjects of child-bearing potential who did not practice efficient contraception during the study. A pregnancy test in blood was performed at screening and before each period with β-human chorionic gonadotropin for females of child-bearing potential. If pregnancy test was positive, the subject had to be immediately excluded from study and followed until delivery
- •History of severe allergy or of asthma at any time.
- •History of cardiovascular dysfunction
- •Hypertension
- •Sick sinus syndrome or known long QT syndrome
- •Presence of QTc  > 440 msec or pronounced sinus bradycardia (<40 bpm/min), even if elicited by sport
- •Dark skin preventing local tolerance assessment or abnormal cutaneous reaction e.g. urticaria or papular dermographism
- •Intense sport activities.
- •Any clinically significant laboratory value on screening that were not within normal range on single repeat
- •Positive hepatitis B & C antigen screen
- •Positive HIV antibody screen or screen not performed
- •Any recent acute illness or sequelae thereof which could expose the subject to a higher risk or might confound the results of the study
- •Treatment in the previous three months with any drug known to have well-defined potential for toxicity to a major organ
- •History of hypersensitivity to any drug if considered as serious
- •History of alcohol or drug abuse
- •Positive qualitative urine drug test at screening
- •Use of any medication in 2 weeks prior to study and throughout study, including aspirin or other over-the-counter preparation.
- •Blood (500 mL) donation or hemorrhage during the previous three months
- •Participation in a clinical trial in the previous 3 months
- •Consumption of a large quantity of coffee, tea or equivalent
- •Present consumption of a large quantity of alcohol or wine or equivalent
- •Psychological status which could have had an impact on subject's ability to give informed consent or behavioral tests
- •Any feature of subject's medical history or present condition which, in the investigator's opinion, could confound the results of the study, complicate its interpretation, or represent a potential risk for the subject
研究组 & 干预措施
Part A: Interferon beta-1a in HSA-free solution
Twelve subjects will participate in 3 periods of part A, receiving 18 MIU biosimilar interferon beta-1a without albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.
干预措施: Interferon beta-1a HSA-free biosimilar (Drug)
Part A: Interferon beta-1a combined with HSA+ solution
Twelve subjects will participate in 3 periods of part A, receiving 18 MIU biosimilar interferon beta-1a with albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.
干预措施: Interferon beta-1a HSA+ biosimilar (Drug)
Part A: Interferon beta-1a in marketed HSA+ solution
Twelve subjects will participate in 3 periods of part A, receiving 18 MIU original interferon beta-1a with albumin as i.v. bolus into a distal port under constant saline infusion as 3 treatments.
干预措施: Interferon beta-1a original (Drug)
Part B: Interferon beta-1a in HSA-free solution
Twelve additional volunteers will participate in part B, receiving 4 x 18 MIU biosimilar interferon beta-1a with albumin as s.c. doses at 48 hours intervals as 3 pre-filled syringes (3 sites 1 cm apart in abdominal wall on each dosing day, alternating right side for odd dose [i.e. dose 1 and 3] and left side for even dose [i.e. dose 2 and 4]).
干预措施: Interferon beta-1a HSA-free biosimilar (Drug)
Part B: Interferon beta-1a in marketed HSA+ solution
Part B: Twelve additional volunteers will participate in part B, receiving 4 x 18 MIU original interferon beta-1a with albumin as s.c. doses at 48 hours intervals as 3 pre-filled syringes (3 sites 1 cm apart in abdominal wall on each dosing day, alternating right side for odd dose [i.e. dose 1 and 3] and left side for even dose [i.e. dose 2 and 4]).
干预措施: Interferon beta-1a original (Drug)
结局指标
主要结局
Composite of interferon beta-1a PK parameters
时间窗: Part A: 0, 2, 5, 10, 15, 20 [min post-dose] and 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 [hours post-dose] / Part B: 0, 1, 2, 3, 4, 6, 12 [hours post-doses] and 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 [hours post-last dose] (Day 7)
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-inf\]) and maximum observed concentration (Cmax) following single dose administration, as well as time to Cmax (tmax; for s.c. injection) will be assessed. Mean residence time (MRT), half-life of elimination (t1/2), clearance (CL), and volume of distribution at steady-state (Vss) will be calculated.
次要结局
- Serum concentration of neopterin (PD marker)(Part A: 0, 6, 12, 24, 48, 72, 168 [hours post-doses] / Part B: 0, 6, 12 [hours post-doses] and 0, 6, 12, 24, 48, 72, 96, 120, 144, 168 [hours post-last dose] (Day 7))
- Number of participants with adverse events (AE)/serious adverse event (SAE) as a measure of safety and tolerability(Up to Day 7)
- Composite of local reactions as a measure of local tolerance(Part A: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 [hours post-dose] and longer if needed and until resolution in case of local reaction / Part B: 0, 1, 2, 4, 6, 12 [hours post-dose] on Day 1 and 7, else daily up to Day 9 longer until resolution)
- Composite of clinical laboratory tests as a measure of safety and tolerability(Screening and 0, 24 [hours post-doses])
- Composite of vital signs as a measure of safety and tolerability(Part A: Screening and 0, 1, 2, 3, 4, 6, 8, 10, 12, 24 [hours post-dose] / Part B: Screening and 0, 1, 2, 3, 4, 6, 12 [hours post-doses], as well as 0, 1, 2, 3, 4, 6, 8, 12, 24 [hours post-last dose] (Day 7))
- Sickness behavior assessment(Part A: 0, 2, 4, 6, 8, 10, 12 [hours post-dose] / Part B: 0, 1, 2, 4, 6, 12 [hours post-dose], as well as 24, 48, 72 [hours post-last dose] (Day 7))
- Electrocardiogram (ECG) as a measure of safety and tolerability(Screening and 0, 3 [hours post-dose])
研究者
Prof. Jérôme Biollaz, MD
Chief Physician
Centre Hospitalier Universitaire Vaudois