Official Title: “CT 5002 An Open-Label, Non-Randomized, Monocentric Phase I Study Evaluating the Pharmacokinetic Profile of RhuDex® Using 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 Type: Interventional

Study Design: Other, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study

Study Primary Completion Date: August 2008

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.

Intervention(s) in this Clinical Trial

• Drug: RhuDex®
  • 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

Primary Measures

• 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
    Safety Issue?: No

Secondary Measures

• To gain further safety and tolerability data of RhuDex®
  • Time Frame: during treatment phase and 28 days afterwards
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Healthy male subjects between 18 and 60 years at the time of enrolment
• 2. Subjects who are sexually active must use adequate contraception for the duration of the study from screening until 12 weeks after the last dose.
• 3. BMI between 18.5 and 29.9 kg/m²
• 4. Written informed consent
• 5. Ability to comply with the requirements of the study

Exclusion Criteria:

• 1. Acute infection at time of enrolment
• 2. History of chronic inflammation, chronic infection, other chronic disease, autoimmune disorders (e.g. diabetes mellitus) or cancer
• 3. Clinically significant abnormal ECG
• 4. Clinically significant abnormal laboratory values (especially in terms of liver or renal insufficiency)
• 5. Clinically significant physical findings
• 6. Major surgery within the last 4 weeks prior to enrolment
• 7. Organ allograft recipient
• 8. Concomitant or planned treatment which would interfere with study results
• 9. 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
• 10. Known allergy against any ingredient of the study medication, meglumine, pantoprazole or bovine milk
• 11. Participation in an investigational trial within 12 weeks prior to enrolment
• 12. Systemic intake of immunosuppressive or immunomodulatory medication or vaccination within 30 days prior to enrolment and for the whole study duration
• 13. Blood loss exceeding 450 mL (including blood donations) within 12 weeks prior to enrolment into the study.
• 14. Medical history of alcohol or drug abuse within the last 2 years or alcohol consumption greater than 21 units per week.
• 15. A positive alcohol breath test
• 16. A positive urine drug screen
• 17. Smokers who smoke > 5 cigarettes or 5 cigars per day
• 18. Presence of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) or HIV-1 or HIV-2 antibodies at screening
• 19. Subject whose partner is pregnant or lactating

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: MediGene

Overall Clinical Trial Officials and Contacts

Stuart Mair, MBChB, DROCG,DCPSA Principal Investigator Charles River Clinical Services Edinburgh Ltd  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00704119

Study ID Number: CT 5002

ClinicalTrials.gov Identifier: NCT00704119

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency