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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00704119
|Charles River Clinical Services Edinburgh Ltd|
|Edinburgh, Scotland, United Kingdom, EH14 4AP|
|Principal Investigator:||Stuart Mair, MBChB, DROCG,DCPSA||INC Research|