Table 1.

Phase I vericiguat study design details

Healthy volunteer study	Co-medicationa	Design	Vericiguat treatmenta
Human mass balance  EudraCT 2013-005115-27	Not applicable	Open-label, non-randomized, non-placebo-controlled	5 mg radiolabeled [14C] SDb
Study investigating DDI potential of vericiguat with agents affecting gastric pH
DDI with omeprazole and magnesium/aluminum hydroxide  EudraCT 2012-000932-25	Pre- and co-administration of omeprazole 40 mg QD for 5 days Co-administration of 10 mL (equivalent to magnesium hydroxide 600 mg/aluminum oxide 900 mg) SD	Randomized, open-label, non-placebo-controlled, three-fold crossover	5 mg SDb
Studies investigating the victim DDI potential of vericiguat
DDI with ketoconazole (multi-pathway inhibitor)  EudraCT 2013-000769-35	Pre- and co-administration of ketoconazole 200 mg BID for 3 days	Randomized, open-label, two-fold crossover	1.25 mg SDc
DDI with rifampicin (multi-pathway inducer)  EudraCT 2016-002330-68	Pre- and co-administration of rifampicin 600 mg QD for 9 days	Non-randomized, non-blinded, non-placebo-controlled, fixed sequence	10 mg SDc
DDI with mefenamic acid (UGT1A9 inhibitor)  EudraCT 2014-000764-17	Pre- and co-administration of mefenamic acid 500 mg followed by MDs of mefenamic acid 250 mg every 6 h for 3 days	Randomized, non-placebo-controlled, open-label, two-fold crossover	2.5 mg SDc
Study investigating the perpetrator DDI potential of vericiguat
DDI with midazolam (CYP3A4 index substrate)  EudraCT 2014-003982-13	Midazolam 7.5 mg SD (alone vs day 4 under vericiguat treatment)	Randomized, non-blinded, non-placebo-controlled, two-fold crossover	10 mg QD for 4 daysc
Studies investigating the DDI potential of vericiguat with drugs used in cardiovascular disease
DDI with warfarin  EudraCT 2014-004880-19	Warfarin 25 mg SD (alone vs day 6 under vericiguat treatment)	Randomized, placebo-controlled, double-blind, two-fold crossover	10 mg QD for 9 daysc
DDI with digoxin  EudraCT 2014-004733-75	Digoxin 0.375 mg QD for 14 days (alone vs days 8–10 under vericiguat treatment)	Randomized, non-blinded, non-placebo-controlled, two-fold crossover with additional fixed treatment period	10 mg QD for 10 daysc
DDI with aspirin  EudraCT 2014-000765-52	Aspirin 500 mg SD (alone vs day 1 under vericiguat treatment) in the main part of the study	Randomized, non-blinded, non-placebo-controlled, three-sequence, three-fold crossover (in the main part of the study)	15 mg SDb
DDI with sacubitril/valsartan  EudraCT 2015-004809-16	Pre- and co-administration of sacubitril/valsartan BID over 41 days (pre-administration dose of 49/51 mg BID for 14 days) followed by sacubitril/valsartan 97/103 mg for 27 days (alone for 13 days and co-administration for 14 days; 97/103 mg BID)	Randomized, single-blind, placebo-controlled	2.5 mg for 14 daysc
Studies investigating the DDI potential of vericiguat with drugs affecting the NO signaling  pathway
DDI with sildenafil  EudraCT 2015-004997-14	Co-administration of sildenafil 25 mg (day 14), 50 mg (day 15), and 100 mg (day 16)	Randomized, placebo-controlled, single-blind	10 mg for 16 daysc

BID twice daily, DDI drug–drug interaction, MD multiple dose, NO nitric oxide, QD once daily, SD single dose, UGT uridine diphosphate-glucuronosyltransferase

^aAll study medications were administered orally

^bVericiguat administered in fasting conditions

^cVericiguat administered in fed conditions