Table 1.
Phase I vericiguat drug–drug interaction studies in healthy subjects
| Study details | Interaction drug | Design |
|---|---|---|
| Aspirin interaction study: EudraCT 2014-000765-52 | ||
| Vericiguat 15 mg SDa | Aspirin 500 mg | Open-label, nonplacebo-controlled |
| Pilot partb | ||
| Vericiguat 15 mg SD | ||
| Main partc | Main part: Three-period, Three-sequence, Threefold crossover | |
| Treatments A, B, and C: | ||
| A: Vericiguat 15 mg (day 1) | ||
| B: Aspirin 500 mg (day –1, day 1) | ||
| C: Aspirin 500 mg (day –1) and vericiguat 15 mg | ||
| SD + aspirin 500 mg (day 1) | ||
| Treatment sequences: | ||
| A-C-B, B-A-C, or C-B-A | ||
| Warfarin interaction study: EudraCT 2014-004880-19 | ||
| Vericiguat 10 mg qd over 9 days | Warfarin 25 mg (priming dose) on day −21; warfarin 25 mg, administered on day 6 | Double-blind, placebo-controlled, twofold crossover design |
| Treatments A and B | ||
| A: Vericiguat plus warfarin | ||
| B: Placebo plus warfarin | ||
| SV interaction study: EudraCT 2015-004809-16 | ||
| Vericiguat 2.5 mg qdd | SV 49/51 mg during run-in phase (bid for 14 days; days 1–14); SV 97/103 mg bid over 27 days (13 days alone [days 15–27]), followed by 14 days in combination with vericiguat or placebo (days 28–41) | Single-blind, placebo-controlled |
| Period 1: SD (day 1) | ||
| Period 2: MD (qd for 14 days; days 28–41) | ||
bid twice daily, MD multiple dose, qd once daily, SD single dose, SV sacubitril/valsartan
aAs bioavailability is lower in the fasted state, vericiguat 15 mg (fasted) was selected to investigate interactions relevant for vericiguat 10 mg (fed)
bNonrandomized part
cRandomized part
dStarting dose of the titration schedule in subsequent phase II and III studies