| Outcome Measures: |
Primary: Number of participants (Healthy Volunteers) with reported adverse events receiving single oral dose of LHW090 as assessment of safety and tolerabiility, In this analysis AE and SAE will be reported, 6 months|Number of participants (Healthy Volunteers) with reported adverse events receiving multiple oral dose of LHW090 as assessment of safety and tolerabiility, In this analysis AE and SAE will be reported, 6 months|Number of participants (patients) with reported adverse events receiving single oral dose of LHW090 as assessment of safety and tolerabiility, In this analysis AE and SAE will be reported, 6 months | Secondary: Pharmacokinetics of LHW090/LHV527 in plasma: observe maximum plasma concentration following LHW090 at steady state in healthy volunteers and patients, In this analysis Cmax will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: time to reach the maximum concentration after administration of LHW090 (Tmax), In this analysis Tmax will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUClast), In this analysis AUClast will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: area under the plasma concentration-time curve from time zero to infinity (AUCinf), In this analysis AUCinf will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: terminal elimination half-life (T1/2), In this analysis T1/2 will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: accumulation ratio (RACC), In this analysis the accumulation ratio will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration (Vd/F), In this analysis apparent volume of distribution during the terminal elimination phase will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in plasma: apparent system clearance from plasma following intravenous administration of iothalamate (CL/F), In this analysis the apparent system clearance from plasma will be reported, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacokinetics of LHW090/LHV527 in urine: apparent system clearance from urine from time 0 - 24 hrs following drug administration (Ae0-24), In this analysis the apparent system clearance by urine will be reported from 0 - 24 hrs post dose, Stage 1, 2 and 4 :0-4, 4-8, 8-12, 12-24, 24-36, 36-48 and 48 - 72 h post dose in Day 1 and Day 14; Stage 3: 0-4, 4-8, 8-12, and 12-24 h post dose|Pharmacokinetics of LHW090/LHV527 in urine: apparent system clearance from urine from time 0 - 72 hrs following drug administration (Ae0-72h), In this analysis the apparent system clearance by urine will be reported from 0 - 72 hrs post dose, Stage 1, 2 and 4 :0-4, 4-8, 8-12, 12-24, 24-36, 36-48 and 48 - 72 h post dose in Day 1 and Day 14; Stage 3: 0-4, 4-8, 8-12, and 12-24 h post dose|Pharmacokinetics of LHW090/LHV527 in urine: apparent renal clearance from urine following drug administration (CLr), In this analysis the apparent system clearance by urine will be reported, Stage 1, 2 and 4 :0-4, 4-8, 8-12, 12-24, 24-36, 36-48 and 48 - 72 h post dose in Day 1 and Day 14; Stage 3: 0-4, 4-8, 8-12, and 12-24 h post dose|Pharmacodynamics of LHW090/LHV527 in serum: post treatment peak and mean area under the plasma concentration-time curve from time zero to 24 hour (AUC0-24h/24h) for cyclic guanosine (cGMP), In this analysis AUC0-24/24h will be reported for single ascending dose healthy volunteers and CRI subjects, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs|Pharmacodynamics of LHW090/LHV527 in serum: post treatment peak and mean area under the plasma concentration-time curve from time zero to 24 hour (AUC0-24h/24h) for atrial natriuretic peptide (ANP), In this analysis AUC0-24/24h will be reported for single ascending dose healthy volunteers and CRI subjects, Within 60 min prior to dosing, post dose: +/- 5 min up to 3 hrs, +/- 10 min from ≥3 hrs to 24hrs, +/- 2 hrs from ≥24 hrs to 72hrs
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