Study to Assess the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of AZD0284 in Healthy Subjects
Condition: Plaque Psoriasis Vulgaris
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 1

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.
    

Detailed 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.
    

Intervention name(s): AZD0284; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral solution, concentration: 2 mg/mL and 15 mg/mL; Placebo matching AZD0284 in the form of an oral solution with water.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Plaque psoriasis vulgaris