Table 1 Five phase I studies of vericiguat in healthy subjects

Relative bioavailability

2011–004,841-42

1.25 mg intact tablet (fasted), 5 mg intact tablet (fed and fasted), 5 mg PEG solution (fasted)

Safety, PD, and PK of

vericiguat intact tablets vs PEG solution

Four-way, crossover design (n = 15)

Healthy, White males

Absolute bioavailability

2015–001,568-20

10 mg tablets (two 5 mg intact tablets; fed, high-fat, high-calorie meal), followed by 20 µg (¹⁴C-labeled) IV infusion over 30 min (4 h post-oral tablet)

Absolute bioavailability of a single oral dose of vericiguat 10 mg (fed state) vs a single IV infusion microdose (20 µg) of ¹⁴C-labeled vericiguat

Non-randomized (all subjects received the same treatment; n = 10)

Healthy, White males

Exploratory dose proportionality

2012–004,839-23

1.25 mg, 2.5 mg, 5 mg, and 10 mg intact tablets (all fed, high-fat, high-calorie meal)

PK and safety of vericiguat 1.25–10 mg (fed state)

Four-way crossover study (n = 15)

Healthy, White males

Pivotal food effect and dose proportionality

2016–000,980-18

2.5 mg, 5 mg, and 10 mg intact tablets (all fed) 10 mg tablets (fasted)

PK dose proportionality of single oral dose of vericiguat 2.5 mg and 5 mg vs 10 mg (fed)

Food effect on PK after single oral dose of 10 mg (fed vs fasted)

Safety of vericiguat

Four-way crossover study (n = 29 [food effect]; n = 27 [dose proportionality])

Healthy, White males

Comparative bioavailability^a

2016–005,074-35

10 mg crushed tablets suspension (fed, high-fat, high-calorie meal)

10 mg intact tablet (fed, high-fat, high-calorie or low-fat, low-calorie meal)

PK of crushed tablet suspension vs intact tablets in fed conditions (high-fat vs low-fat meal)

Six-way crossover study (n = 27)

Healthy, White males