A Four-Part Phase-1 Study Investigating the Tolerability, Safety and Pharmacokinetics (PK) of MBS2320 in Healthy Subjects and in Subjects With Rheumatoid Arthritis (RA) Also Treated With Methotrexate
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 3
- 主要终点
- Safety and tolerability (incidence of all grade adverse events and dose limiting toxicities during the observation period and/or study treatment periods)
研究概览
简要总结
Rheumatoid arthritis (RA) affects 1 percent of the population worldwide and up to 40 percent of patients don't respond to current treatments. MBS2320, the drug being tested in this trial, represents a new approach to treating RA, with the potential not only to reduce levels of inflammation but to also directly inhibit bone damage.The aim of this study is to test the safety of MBS2320 in healthy volunteers, to find out how MBS2320 levels change in the blood with dose, and to test the safety and compatibility of giving MBS2320 to patients with RA in combination with an existing treatment, methotrexate.
详细描述
The study will be conducted in 4 parts (parts A to D). The principal aim of this study is to obtain safety and tolerability data when MBS2320 is administered orally as single and multiple doses to healthy subjects (parts A to C). The effect of MBS2320 on the pharmacokinetics (PK) of the first-line rheumatoid arthritis (RA) therapy, methotrexate (MTX), and the effect of MTX on the PK of MBS2320, will also be evaluated in a cohort consisting of subjects with RA (Part D).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parts A, B, and C.
- •Healthy males or females between 18 and 60 years of age.
- •A body mass index (BMI) between 18.0 and 30.0 kg/m
- •Female subjects will be of non-childbearing potential or postmenopausal as defined by the protocol.
- •Female subjects must not be pregnant.
- •Subjects will be otherwise healthy males or females with a diagnosis of RA between 18 and 70 years of age.
- •Subjects will have a BMI between 18.0 and 30.0 kg/m
- •Female subjects must not be pregnant.
- •Subjects must have been treated with, and tolerated, oral or subcutaneous MTX for a minimum of 3 months prior to screening entry.
排除标准
- •Parts A, B, and C.
- •Male subjects who do not agree to use appropriate contraception.
- •Female subjects who are receiving HRT who do not agree to use appropriate contraception.
- •Subjects who have donated blood in the 3 months, plasma in the 7 days or platelets in the 6 weeks prior to screening.
- •Subjects who consume more than the permitted alcohol requirement, who have a significant history of alcoholism or drug/chemical abuse.
- •Subjects who are unwilling to abstain from alcohol as required.
- •A positive urine drug screen, alcohol breath test at screening or first admission.
- •Subject has received a live virus vaccination within the 30 days prior to first dose administration.
- •Subjects with a positive test for tuberculosis.
- •Additional Part D Exclusions
- •Subjects who have received any medication (except MTX) known to chronically alter drug absorption or elimination processes within 30 days prior to the first dose administration.
- •Subjects currently taking any medications other than those allowed per protocol guidelines.
研究组 & 干预措施
Single Ascending Dose and Food Effect
Part A will be a single-dose, sequential-group, double-blind, placebo-controlled study of MBS2320.
干预措施: MBS2320 (Drug)
Single Ascending Dose and Food Effect
Part A will be a single-dose, sequential-group, double-blind, placebo-controlled study of MBS2320.
干预措施: Placebo (Drug)
Multiple Ascending Dose
Part B will be a multiple-dose, sequential-group, double-blind, placebo-controlled study to investigate 3 planned dose levels.
干预措施: MBS2320 (Drug)
Multiple Ascending Dose
Part B will be a multiple-dose, sequential-group, double-blind, placebo-controlled study to investigate 3 planned dose levels.
干预措施: Placebo (Drug)
Relative Bioavailability
Part C will be an open-label, randomised, 2-period crossover relative bioavailability study of MBS2320 in capsules or suspension. The intention is to enrol 8 healthy subjects. Each subject will participate in 2 treatment periods.
干预措施: MBS2320 (Drug)
Relative Bioavailability
Part C will be an open-label, randomised, 2-period crossover relative bioavailability study of MBS2320 in capsules or suspension. The intention is to enrol 8 healthy subjects. Each subject will participate in 2 treatment periods.
干预措施: Placebo (Drug)
Drug-Drug Interaction with Methotrexate
Part D will be a multiple dose study incorporating an open-label, fixed-sequence drug-drug interaction between MBS2320 and methotrexate and biomarker evaluation.
干预措施: MBS2320 (Drug)
Drug-Drug Interaction with Methotrexate
Part D will be a multiple dose study incorporating an open-label, fixed-sequence drug-drug interaction between MBS2320 and methotrexate and biomarker evaluation.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Safety and tolerability (incidence of all grade adverse events and dose limiting toxicities during the observation period and/or study treatment periods)
时间窗: Within 7 days
次要结局
- Study Parts A, B and C - Peak Plasma Concentration (Cmax) of MBS2320(Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose)
- Study Parts A, B and C Time to peak plasma concentration (Tmax) of MBS2320(Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose)
- Study Parts A, B and C - Area under the plasma concentration versus time curve (AUC) of MBS2320(Part A and C - Up to 72hrs post dose, Part B - Up to 72 hrs post day 14 dose)
- Part D - Peak Plasma Concentration (Cmax) of MBS2320 and methotrexate(During the study treatment period)
- Part D - Area under the plasma concentration versus time curve (AUC) of MBS2320 and methotrexate(During the study treatment period)
- Part D - Time to peak plasma concentration (Tmax) of MBS2320 and methotrexate(During the study treatment period)
- Part D - Half-life (T1/2) of MBS2320 and methotrexate(During the study treatment period)
- Part D - Early response biomarkers of disease activity and bone turnover(Day 1 and 16.)