Study Evaluating the Pharmacokinetic Profile of RhuDex® in a Tablet Formulation

March 23, 2010 updated by: MediGene

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 Overview

Status

Terminated

Conditions

Pharmacokinetics

Intervention / Treatment

Drug: RhuDex®

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United Kingdom
- Scotland
  - Edinburgh, Scotland, United Kingdom, EH14 4AP
    - Charles River Clinical Services Edinburgh Ltd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	24 -96h pharmakokinetic laboratory values

Secondary Outcome Measures

Outcome Measure	Time Frame
To gain further safety and tolerability data of RhuDex® Time Frame: during treatment phase and 28 days afterwards	during treatment phase and 28 days afterwards

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MediGene

Investigators

Principal Investigator: Stuart Mair, MBChB, DROCG,DCPSA, Syneos Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

July 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

June 23, 2008

First Submitted That Met QC Criteria