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Study to Assess the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of AZD0284 in Healthy Subjects

2016-11-30 15:45:13 | BioPortfolio

Summary

Plaque psoriasis vulgaris is a chronic inflammatory skin disorder, affecting 1-3% of the population in Europe and the United States of America (USA) and represents one of the most prevalent immune inflammatory diseases. AZD0284 is a potent selective inverse agonist of RORg, which is being developed for the management of psoriasis. The current Phase 1 study investigates the safety, tolerability, food effect, pharmacokinetic (PK) and pharmacodynamic (PD) properties of single and repeated doses of AZD0284. The study will be conducted in healthy subjects. The study will be divided into 2 parts: Part 1 (SAD) and Part 2 (MAD), with Part 1 being split into 2 sub-parts: 1A (fasting) and 1B (fed). The results from this study will form the basis for decisions on future studies. The study will help to identify appropriate, well-tolerated doses that can be administered in subsequent studies in patients with psoriasis.

Description

Plaque psoriasis vulgaris is a chronic inflammatory skin disorder. There are 2 key abnormalities in psoriasis, hyper proliferation of keratinocytes and an inflammatory cell infiltrate, which includes; dendritic cells (DCs), macrophages, natural killer (NK) T cells, mast cells, T cells and neutrophils. There is strong evidence that T cells have an important role in psoriasis, including the fact that T-cell targeted agents are effective in psoriasis therapy. This study is the first time AZD0284 will be given to humans. The current Phase 1 study investigates the safety, tolerability, food effect, pharmacokinetic (PK) and pharmacodynamic (PD) properties of single and repeated doses of AZD0284. The study will be conducted in healthy subjects to avoid interference from disease processes or other drugs. The study will be divided into 2 parts: Part 1 (SAD) and Part 2 (MAD), with Part 1 being split into 2 sub-parts: 1A (fasting) and 1B (fed). The secondary and safety pharmacology of AZD0284 has been investigated using both in vitro and in vivo models. Screening of AZD0284 in a diverse set of in vitro radiolig and binding, enzyme, functional and electrophysiological assays including cardiac ion channels did not identify any off-target activities likely to be relevant in or near the therapeutic exposure range. The inclusion and exclusion criteria are defined such that the selected subjects will be free of any significant illness when included in the study. The selected starting dose for the SAD part (Part 1A) of the study is 4.0 mg AZD0284 (oral solution). The maximum allowed exposure based on the toxicology studies is 127 μmol*h/L (total AUC(0-24,ss)) or 7.35 μmol/L (total Cmax). In Part 1A (SAD study), 6 dose levels and in Part 2 (MAD study), 3 dose levels are planned. In either part, up to 2 additional doses may be added if needed. The results from this study will form the basis for decisions on future studies. The study will help to identify appropriate, well-tolerated doses that can be administered in subsequent studies in patients with psoriasis.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Conditions

Plaque Psoriasis Vulgaris

Intervention

AZD0284, Placebo

Location

Research Site
London
United Kingdom

Status

Not yet recruiting

Source

AstraZeneca

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-11-30T15:45:13-0500

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Medical and Biotech [MESH] Definitions

A humanized monoclonal antibody that binds to IL-12 and IL-23 and is used as a DERMATOLOGIC AGENT in the treatment of patients with plaque PSORIASIS who have not responded to other therapies.

Human immune-response, D-related antigen encoded by the D locus on chromosome 6 and found on lymphoid cells. It is strongly associated with celiac disease and psoriasis vulgaris.

Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called ENDARTERECTOMY.

An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).

The term applied to a group of relatively uncommon inflammatory, maculopapular, scaly eruptions of unknown etiology and resistant to conventional treatment. Eruptions are both psoriatic and lichenoid in appearance, but the diseases are distinct from psoriasis, lichen planus, or other recognized dermatoses. Proposed nomenclature divides parapsoriasis into two distinct subgroups, PITYRIASIS LICHENOIDES and parapsoriasis en plaques (small- and large-plaque parapsoriasis).

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