A Three Part, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of Inhaled and Intravenous GSK2862277 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2
研究概览
简要总结
This will be a 3 part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2862277 administered via inhalation (IH) or intravenous (IV) routes in healthy subjects.
Part 1 of this study will involve an initial assessment of safety, tolerability and pharmacokinetics of GSK286227, via single escalating intravenous doses, compared to a predecessor molecule, GSK1995057. After completion of Part 1 an interim data review will occur which will assess key comparability criteria to inform progression to Part 2 of the study.
Part 2 of the study will involve single doses of GSK2862277 at a level predicted to be at or close to therapeutic dose levels. Part 2 will investigate both intravenous and inhaled routes of administration, in sequential manner, respectively. An interim data review will also occur after completion of Part 2, where all data accumulated previously will be assessed to examine appropriateness to progress to Part 3.
Part 3 of the study will involve 5 days of repeat dosing via both inhaled and intravenous routes using the same dose administered in Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- •Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Subject is positive at screening for HAVH autoantibodies against GSK1995057 (Part 1 only).
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- •A positive pre-study drug/alcohol screen.
- •A positive test for human immunodeficiency virus (HIV) antibody.
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
排除标准
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- •A positive pre-study drug/alcohol screen.
- •A positive test for human immunodeficiency virus (HIV) antibody.
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day
研究组 & 干预措施
Part 1: Cohort 1a
Single IV dose of GSK2862277 as a continuous infusion over 2 hours.
干预措施: Single IV dose of GSK2862277 (Drug)
Part 1: Cohort 1b
Single IV dose of GSK2862277 as a continuous infusion over 3 hours.
干预措施: Single IV dose of GSK2862277 (Drug)
Part 1: Cohort 1c
Single IV dose of GSK2862277 as a continuous infusion over 3 hours.
干预措施: Single IV dose of GSK2862277 (Drug)
Part 2: Cohort 2a GSK2862277
Single IV dose of GSK2862277 as a continuous infusion over 1 hour.
干预措施: Single IV dose of GSK2862277 (Drug)
Part 2: Cohort 2a Placebo
Matching placebo will be administered as a continuous IV infusion over 1 hour.
干预措施: Matching placebo single dose IV infusion (Drug)
Part 2: Cohort 2b GSK2862277
Single IH dose of GSK2862277.
干预措施: Single IH dose of GSK2862277 (Drug)
Part 2: Cohort 2b Placebo
Matching placebo will be administered.
干预措施: Matching placebo single dose IH (Drug)
Part 3: Cohort 3a GSK2862277
IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days.
干预措施: Repeat IV dose of GSK2862277 (Drug)
Part 3: Cohort 3a Placebo
Matching placebo will be administered as IV infusion over 1 hour daily for 5 days.
干预措施: Matching placebo repeat dose IV infusion (Drug)
Part 3: Cohort 3b GSK2862277
Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days.
干预措施: Repeat IH dose selected of GSK2862277 from Part 2 (Drug)
Part 3: Cohort 3b Placebo
Matching placebo will be administered as IH daily for 5 days.
干预措施: Matching placebo repeat dose IH (Drug)
结局指标
主要结局
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2
时间窗: Up to 42 days
Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study.
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3
时间窗: Up to 42 days
Safety and tolerability parameters will include recording of AEs, throughout the study.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2
时间窗: Up to 42 days
Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature.
Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1
时间窗: Up to 42 days
Blood samples will be collected for assessment of plasma cytokines.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2
时间窗: Up to 42 days
Laboratory tests will include haemogram, clinical chemistry, urine examination.
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3
时间窗: Up to 42 days
Vital signs will include BP, heart rate respiration rate and body temperature.
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3
时间窗: Up to 42 days
Safety data will include ECG readings obtained at each timepoint during the study.
Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3
时间窗: Up to 42 days
Laboratory tests will include haemogram, clinical chemistry, urine examination.
Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3
时间窗: Up to 60 days
Presence of anti GSK2862277 binding antibodies will be evaluated.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2
时间窗: Up to 42 days
Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study.
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2
时间窗: Up to 42 days
Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3
时间窗: Up to 42 days
Spirometry monitoring will include FEV1 and FVC.
Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
时间窗: Up to 60 days
Presence of anti GSK2862277 binding antibodies will be evaluated.
次要结局
- Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a(Up to 48 hours post dose)
- PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a(Up to 48 hours post last dose)
- Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2(Up to 48 hours post dose)
- Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2(Up to 48 hours post last dose)
- Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c(Up to 12 hours post dose)
- PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b(Up to 48 hours post last dose)
- PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1(Up to 48 hours post last dose)
- Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3(Up to 48 hours post last dose)