A Single Ascending Dose Study To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of AZD9567.
Condition: Safety; Tolerability; Pharmacokinetics; Pharmacodynamics; Healthy Subjects; Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: AZD9567 Monohydrat; Placebo oral suspension/ Placebo capsule; Prednisolone
Intervention description: AZD9567 oral suspension 0.5 to 10 mg/ml; Matching placebo; Prednisolone 60mg oral capsules (12 capsules of 5 mg each).
Intervention MeSH terms: Prednisolone
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 72.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: AZD9567; Healthy subjects; Phase 1; placebo controlled; single ascending dose; Pharmacokinetics; Pharmacodynamics; Rheumatoid Arthritis

Summary:

      This is a Phase I, first-in-human (FIH), randomized, single-blind, placebo-controlled, single
      ascending dose sequential group study in healthy male subjects. The objectives are to study
      the safety, tolerability, pharmacokinetics and effects on glucose homeostasis
      (pharmacodynamics) of AZD9567, an oral differentiated non-steroidal selective glucocorticoid
      receptor modulator (SGRM). The study will also assess the safety, tolerability,
      pharmacokinetics (PK) and pharmacodynamics (PD) of prednisolone 60 mg in comparison with high
      doses of AZD9567 and placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of signed and dated, written informed consent prior to any study specific
             procedures.

          -  Healthy male subjects aged 18 to 55 years with suitable veins for cannulation or
             repeated venipuncture.

          -  Have a body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50
             kg and no more than 100 kg inclusive.

          -  Normal OGTT at screening (<7.8 mmol/L).

          -  Serum cortisol levels within normal limits at screening (collected as part of the
             clinical chemistry panel).

          -  Able to understand, read and speak the German language.

        Exclusion Criteria:

          -  History of any clinically important disease or disorder which, in the opinion of the
             Investigator, may either put the subject at risk because of participation in the
             study, or influence the results or the subject's ability to participate in the study.

          -  History or presence of gastrointestinal (GI), hepatic or renal disease, or any other
             condition known to interfere with absorption, distribution, metabolism, or excretion
             of drugs.

          -  History of or active or latent tuberculosis (TB), or at risk for having acquired TB
             (social workers or prison staff in countries with endemic rates of TB, having lived
             with patients with known TB).

          -  History suggesting abnormal immune function, as judged by the investigator.

          -  Any contraindications to be treated with prednisolone (allergy to any ingredient,
             systemic fungal infection, certain type of malaria, inflammation of the optic nerve,
             or herpes infection of the eye, scheduled to have a live or attenuated live
             vaccination or taking mifepristone).

          -  History of severe affective disorder including depressive or manic-depressive illness
             them self or first degree relatives.

          -  History of previous steroid psychosis

          -  Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks
             of the first administration of IMP.

          -  Any latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes,
             urinary tract infection) or at risk of infection (surgery, trauma, or significant
             infection), or history of skin abscesses within 90 days prior to the first
             administration of IMP.

          -  Any clinically important laboratory abnormalities (clinical chemistry, hematology,
             coagulation or urinalysis results), as judged by the investigator. In particular a
             subject with an abnormal value in alkaline phosphatase (ALP), alanine aminotransferase
             (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT),
             creatinine, thyroid-stimulating hormone (TSH), fasting glucose, International
             Normalised Ratio (INR), haemoglobin (Hb), white blood cell (WBC), absolute neutrophil
             or platelet count will be excluded.

          -  Any positive result on screening for serum hepatitis B surface antigen (HBsAg),
             hepatitis C antibody and human immunodeficiency virus (HIV).

          -  Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
             Systolic BP (SBP) < 90mmHg or ≥ 140 mmHg, Diastolic BP (DBP) < 50mmHg or ≥ 90 mmHg,
             Pulse < 45 or > 85 beats per minute (bpm).

          -  Any clinically important abnormalities in rhythm, conduction or morphology of the
             resting ECG and any clinically important abnormalities in the 12-lead ECG, as
             considered by the investigator that may interfere with the interpretation of QTc
             interval changes, including abnormal ST-T-wave morphology, particularly in the
             protocol defined primary lead or left ventricular hypertrophy.

          -  Prolonged QTcF > 450 ms or family history of long QT syndrome.

          -  PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there
             is no evidence of ventricular pre-excitation).

          -  PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while
             asleep is not exclusive) or third degree AV block, or AV dissociation