Conditions: Safety Tolerability Pharmacokinetics Pharmacodynamics Healthy Subjects Rheumatoid Arthritis
Keywords: AZD9567 Healthy subjects Phase 1 placebo controlled single ascending dose Pharmacokinetics Pharmacodynamics Rheumatoid Arthritis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 72
Healthy volunteers: yes

Brief 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.

Detailed description:
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. Additional exploratory variables (Inflammation biomarkers, ECG modelling and taste assessment) will also be evaluated. 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. The study will be conducted at a single study centre with a planned number of subjects of up to 72 healthy males, aged 18 to 55 years.

Arms:
arm 1: In Part A: up to 8 cohorts with single ascending doses (starting at 2 mg up to 155 mg).

In Part B: one cohort with a single dose arm 2: Subjects randomized to placebo in the first 8 cohorts will receive the same dose volume of oral suspension as subjects on AZD9567 and subjects randomized to placebo in cohort 9(prednisolone cohort) will receive the same number of capsules as subjects on prednisolone. arm 3: Within each cohort 6 subjects will be randomized to receive prednisolone 60mg oral capsules and 2 subjects randomized to receive matching placebo in a fasted state.

Sentinel dosing will not be employed for the prednisolone cohort. The SRC will not be required to evaluate the prednisolone cohort. This cohort can be performed at any time during clinical execution of the study provided the protocol amendment was approved.

Interventions: intervention 1: AZD9567 Monohydrat intervention 2: Placebo oral suspension/ Placebo capsule intervention 3: Prednisolone
Intervention descriptions: intervention 1: AZD9567 oral suspension 0.5 to 10 mg/ml intervention 2: Matching placebo intervention 3: Prednisolone 60mg oral capsules (12 capsules of 5 mg each).

Protocol document: