The objective of this study is to evaluate the dose-ranging response in safety and efficacy of R115866 0.5mg, 1mg and 2mg and R115866 placebo given once daily for the treatment of subjects with plaque psoriasis to select a dose for further clinical…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is success in the PASI, defined as a 75% or
greater reduction from baseline (Visit 2) at the end of treatment Visit 6 (week
12).
Secondary outcome
The secondary efficacy endpoint is success in the PASI50 defined as a >=50%
reduction in score relative to the baseline PASI (Visit 2).
Safety parameters:
All reported adverse events will be summarized by the number and percentage of
subjects reporting adverse events, system organ class, preferred term,
intensity, and relationship to study medication.
Laboratory parameters:
For the clinical laboratory tests including hormone levels, descriptive
statistics will be presented by treatment and visit. Additionally, shift
tables which show the number of subjects with results that are low, normal, or
high at Visit 1 versus post-Visit 1 will be tabulated by treatment and visit.•
Results of the ophthalmic tests performed at Visits 1 and 6 will be presented
for the percentage and number of subjects with abnormal corneal opacity,
abnormal corneal surface or abnormal eye dryness.
Audiology parameters:
Audiology test results will be performed at Visits 1 and 6. The frequency and
percentage of subjects in normal, mild and abnormal hearing categories will be
tallied. Additionally, shift tables for Visit 6 vs. Visit 1 will be tabulated.
Psychiatric parameters:
The results of the psychiatric evaluation of depression at Visits 1, 5 and 6
will be displayed as the percentage and number of subjects with significant
clinical depression (defined as a score on the CES-D >=16)
Background summary
R115866 is a second generation all-trans retinoic acid metabolism blocking
agent (RAMBA). R115866 is a novel triazole derivative with cytochrome P-450
inhibiting properties with high specificity against hydroxylases involved in
the metabolic inactivation pathway of all-trans retinoic acid (RA). As a result
of its cytochrome P-450 inhibiting properties, treatment with R115866 leads to
enhanced tissue levels of endogenous RA thereby exerting distinct retinoid-like
effects (e.g., formation of a granular layer and the transformation of the
parakeratotic type of keratinization to the orthokeratotic type in the scale
regions of murine tail epidermis)8 in vivo.
This property and the well-known modulating effects of RA on epithelial growth
and differentiation indicate R115866 is potentially useful for disorders
associated with or due to an aberrant keratinization, such as psoriasis.
Study objective
The objective of this study is to evaluate the dose-ranging response in safety
and efficacy of R115866 0.5mg, 1mg and 2mg and R115866 placebo given once daily
for the treatment of subjects with plaque psoriasis to select a dose for
further clinical development.
Study design
This is a multi-center, randomized, evaluator-blind, placebo-controlled,
parallel-group study of the safety and efficacy of R115866 0.5mg, 1mg and 2mg
and R115866 placebo in the treatment of severe plaque psoriasis. Subjects with
plaque psoriasis on >=10% body surface area (BSA) with a Psoriasis Area and
Severity Index (PASI) of >=10
Intervention
Subjects will be randomized to R115866 0.5mg, R115866 1mg, R115866 2mg or
R115866 placebo. Subjects will take the assigned study medication once daily
for 12 weeks. The 12-week treatment phase will be followed by an 8-week
no-treatment follow up phase.
Study burden and risks
During Visit 1 patient will give informed consent, prior to any study related
procedures. Also the Medical history will be discussed. Clinical evaluation
will be done every visit.
Also 8-hour fasting routine clinical laboratory and select hormone sampling at
visits 1, 4, 5, 6 and 8 (weeks -2, 4, 8, 12 and 20) will be taken.
Ophthalmologic and audiology evaluations: Visits 1 and 6 (weeks -2 and 12),
psychiatric evaluations: Visits 1, 5 and 6 (weeks -2, 8 and 12),
Electrocardiogram (ECG): Visits 1, 4, 5 and 6 (weeks -2, 4, 8 and 12) will be
done.
All these procedures are standard procedures for the hospitals particpating in
this study.
Platte Akker 38
4847KP
Nederland
Platte Akker 38
4847KP
Nederland
Listed location countries
Age
Inclusion criteria
Subject must be 18 years of older. Subject should be male or female not of childbearing potential. Subject should have a clinical diagnose of plaque psoriasis with a BSA of more then 10% and a PASI of more then 10.
Exclusion criteria
Subject has a history of sensitivity to any of the ingredients in the study medication
Subject is currently participating in, or has within the 30 days prior to the clinical trial participated in an investigational clinical trial.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2005-004623-19-NL |
| CCMO | NL12199.091.06 |