CT 5002 An Open-label, Non-randomized, Monocentric Phase I Study Evaluating the Pharmacokinetic Profile of RhuDex® Using a Tablet Formulation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- MediGene
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- To assess the relationship between the dose of RhuDex® administered and the plasma concentrations achieved following single and repeated doses under fed and/or fasted conditions and with/without administration of pantoprazole
研究概览
简要总结
RhuDex® (code number AV1142742) is a novel, orally bioavailable, low molecular weight modulator of co-stimulation of T lymphocytes. RhuDex® binds to the protein CD80 (also known as B7-1) on the surface of antigen-presenting cells and inhibits its interaction with CD28 (but not with CTLA-4) presented by CD4+ T lymphocytes.
RhuDex® is being developed for the treatment of rheumatoid arthritis. To improve oral bioavailability, the study drug has to be co-administered with an alkaline buffer that increases gastric pH values. In previous in vitro and phase I studies, meglumine has been identified as the most effective buffer. Study CT 5002 is designed to evaluate the bioavailability of four increasing doses of RhuDex®, combined with a fixed amount of meglumine using a tablet formulation, under fed and fasted conditions as well as with co-administration of the proton pump inhibitor pantoprazole. Furthermore, dose/plasma concentration proportionality for single dosing and accumulation effects for repeat dosing of RhuDex® will be evaluated.
详细描述
This is an open-label, non-randomized, monocentric Phase I study to evaluate the pharmacokinetic profile of single-dosed and repeat-dosed RhuDex® using a tablet formulation as well as to assess the effect of food and the effect with co-administration of a proton pump inhibitor on the bioavailability of RhuDex®.
12 healthy male subjects will receive study medication in 8 different treatment periods in 4 subsequent steps A, B, C and D.
Within steps A and B, the subjects will receive different treatments (4 in A and 2 in B), sequentially. There will be a wash-out period of at least 4 days between each of the 8 different treatments/treatment periods of steps A, B, C and D.
In Step A, each subject will receive increasing doses of RhuDex® in 4 subsequent treatments. In Step B, each subject will receive 2 different doses of RhuDex® preceded by pantoprazole intake, in 2 subsequent treatments, and in Step C the RhuDex® dosing will be preceded by a standardized high-fat, high-calorie meal. In Step D, RhuDex® will be administered twice daily for 7 days.
For assessing the pharmacokinetic profile of RhuDex® in steps A, B and C, blood samples will be collected prior to and at different intervals after RhuDex® administration. In step D, blood samples will be collected on Days 1, 2, 4 and 7. Cmin, Cmax, tmax, t½ term, CL/F, AUC(0-t), and AUC(0-∞) of RhuDex® will be analyzed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects between 18 and 60 years at the time of enrolment
- •Subjects who are sexually active must use adequate contraception for the duration of the study from screening until 12 weeks after the last dose.
- •BMI between 18.5 and 29.9 kg/m²
- •Written informed consent
- •Ability to comply with the requirements of the study
排除标准
- •Acute infection at time of enrolment
- •History of chronic inflammation, chronic infection, other chronic disease, autoimmune disorders (e.g. diabetes mellitus) or cancer
- •Clinically significant abnormal ECG
- •Clinically significant abnormal laboratory values (especially in terms of liver or renal insufficiency)
- •Clinically significant physical findings
- •Major surgery within the last 4 weeks prior to enrolment
- •Organ allograft recipient
- •Concomitant or planned treatment which would interfere with study results
- •Any systemic medical treatment, including over the counter products and dietary supplements such as iodine, fluoride or vitamins, within one week before and during the study course
- •Known allergy against any ingredient of the study medication, meglumine, pantoprazole or bovine milk
- •Participation in an investigational trial within 12 weeks prior to enrolment
- •Systemic intake of immunosuppressive or immunomodulatory medication or vaccination within 30 days prior to enrolment and for the whole study duration
- •Blood loss exceeding 450 mL (including blood donations) within 12 weeks prior to enrolment into the study.
- •Medical history of alcohol or drug abuse within the last 2 years or alcohol consumption greater than 21 units per week.
- •A positive alcohol breath test
- •A positive urine drug screen
- •Smokers who smoke > 5 cigarettes or 5 cigars per day
- •Presence of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) or HIV-1 or HIV-2 antibodies at screening
- •Subject whose partner is pregnant or lactating
结局指标
主要结局
To assess the relationship between the dose of RhuDex® administered and the plasma concentrations achieved following single and repeated doses under fed and/or fasted conditions and with/without administration of pantoprazole
时间窗: 24 -96h pharmakokinetic laboratory values
次要结局
- To gain further safety and tolerability data of RhuDex®(during treatment phase and 28 days afterwards)