Table 1.

Overview of the Apararenone Phase 1 Studies in This Analysis

Study 1: Apararenone PK (single dose, effects of food, sex, age, and race; and multiple doses) and PD (multiple doses)
Design	Randomized, double‐blind, placebo‐controlled
Subjects	Healthy male volunteers (except part 2.1, which was conducted in women); all were Caucasian (except part 2.3, which was conducted in Blacks of African/Caribbean descent)
Age	18–55 years (except in part 2.2, which was conducted in subjects aged ≥65 years)
Body weight	Women ≥50 kg, men ≥60 kg
Data collection	PK, safety, tolerability, PD
Apararenone doses	Part 1 — single ascending doses of 3.75, 10, 20, 40, 80, 160, 320, and 640 mg (at each dose, n = 6 plus 2 matched placebo recipients; fasting state [part 1.1], then fed state [part 1.2])
	Part 2.1 — single dose of 20 mg (n = 6) or placebo (n = 2) in women aged 18–55 years
	Part 2.2 — single dose of 20 mg (n = 6) or placebo (n = 2) in men aged ≥65 years
	Part 2.3 — single dose of 20 mg (n = 6) or placebo (n = 2) in men of Black African/Caribbean origin
	Part 3.1 — daily doses of 10, 20, or 40 mg/day (days 1–14) in men; at each dose, n = 8 plus 2 matched placebo recipients
	Part 3.2 — loading dose of 320 mg (day 1), followed by 10 mg/day (days 2–14) in men; n = 8 plus 2 matched placebo recipients
	Part 3.3 — loading dose of 320, 80, or 40 mg (day 1), followed by 20, 5, or 2.5 mg/day, respectively (days 2–14) (males; at each dose, n = 8 plus 2 matched placebo recipients)

Study 2: Single‐dose study in healthy Japanese men
Design	Randomized, double‐blind, placebo‐controlled
Subjects	Healthy Japanese men
Age	20–55 years
Body weight	≥60 kg
Data collection	PK, safety
Apararenone doses	Single dose of 5, 10, 20, or 320 mg (at each dose, n = 6 plus 2 matched placebo recipients)

Study 3: Study of PD effects of single‐dose apararenone (after fludrocortisone challenge; eplerenone active control)
Design	Randomized, double‐blind, placebo‐controlled
Subjects	Healthy Caucasian male volunteers
Age	18–55 years
Body weight	≥60 kg
Data collection	PK, safety, tolerability, PD
Apararenone doses	Part 1 — single dose of apararenone 160 mg (n = 9), placebo (n = 4), or eplerenone 200 mg (n = 9)
	Part 2 — single dose of apararenone 640 mg (n = 9) or placebo (n = 2)
	Fludrocortisone challenge (in parts 1 and 2) — the first fludrocortisone dose (1.0 mg) was administered 9 hours predose (day −1), then fludrocortisone 0.5 mg was administered at the same time as the investigational product (day 1) and 16 hours postdose; and fludrocortisone 0.1 mg was administered 2, 4, 6, 8, 10, 12, 14, and 24 hours postdose

PD, pharmacodynamics; PK, pharmacokinetics.