Study Evaluating the Pharmacokinetic Profile of RhuDex® in a Tablet Formulation - Full Text View

Sponsor:	MediGene
Information provided by:	MediGene
ClinicalTrials.gov Identifier:	NCT00704119

Purpose

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.

Condition	Intervention	Phase
Pharmacokinetics	Drug: RhuDex®	Phase I

Study Type:	Interventional
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

Further study details as provided by MediGene:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To gain further safety and tolerability data of RhuDex® [ Time Frame: during treatment phase and 28 days afterwards ] [ Designated as safety issue: Yes ]

Enrollment:	12
Study Start Date:	May 2008
Study Completion Date:	August 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Intervention Details:

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

Other Name: AV1142742

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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704119

Locations

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

Sponsors and Collaborators

MediGene

Investigators

Principal Investigator:

Stuart Mair, MBChB, DROCG,DCPSA

Kendle International

More Information

No publications provided

Responsible Party:	Prof. HodaTawfik, Clinical Project Manager, MediGene AG
ClinicalTrials.gov Identifier:	NCT00704119 History of Changes
Other Study ID Numbers:	CT 5002
Study First Received:	June 23, 2008
Last Updated:	March 23, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by MediGene:

Rhudex
pharmacokinetic study

ClinicalTrials.gov processed this record on February 09, 2012