Study Evaluating the Pharmacokinetic Profile of RhuDex® in a Tablet Formulation
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.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||CT 5002 An Open-label, Non-randomized, Monocentric Phase I Study Evaluating the Pharmacokinetic Profile of RhuDex® Using a Tablet Formulation|
- 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 [ Time Frame: 24 -96h pharmakokinetic laboratory values ] [ Designated as safety issue: No ]
- To gain further safety and tolerability data of RhuDex® [ Time Frame: during treatment phase and 28 days afterwards ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2008|
|Study Completion Date:||August 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
- Treatment A.1: 31.65 mg RhuDex® once N=12
- Treatment A.2: 63.33 mg RhuDex® once N=12
- Treatment A.3: 126.63 mg RhuDex® once N=12
- Treatment A.4: 253.26 mg RhuDex® once N=12
- Treatment B.1: 31.65 mg RhuDex® once N=12
- Treatment B.2: selected dose of RhuDex® once N=12
- Treatment C: selected dose of RhuDex® once N=12
- Treatment D: selected dose of RhuDex® twice daily for 6 days N=12
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.
Safety will be evaluated by regular observation and documentation of AEs, vital signs, physical examination, ECG, and laboratory parameters.
|Charles River Clinical Services Edinburgh Ltd|
|Edinburgh, Scotland, United Kingdom, EH14 4AP|
|Principal Investigator:||Stuart Mair, MBChB, DROCG,DCPSA||INC Research|