Study: NCT04649229

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: LCZ 696
Description: Treatment with LCZ696 is unblinded in this study. After the two acute study days, subjects will be provided LCZ696 50 mg bid for two weeks. At the end of those two weeks subjects will report to the Clinical Research Center (CRC) for a dose escalation visit. If their tolerance, blood pressure, potassium, and eGFR meet escalation criteria they will be given LCZ696 100 mg bid for three weeks. (If they do not meet escalation criteria they will be continued on LCZ696 50 mg bid.) After three weeks, they will return to the CRC for the next escalation visit. If they meet criteria for escalation they will be given LCZ 200 mg bid for ten days. (If they do not meet escalation criteria they will be continued on the highest tolerated dose).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: LCZ 696
Description: Treatment with LCZ696 is unblinded in this study. After the two acute study days, subjects will be provided LCZ696 50 mg bid for two weeks. At the end of those two weeks subjects will report to the Clinical Research Center (CRC) for a dose escalation visit. If their tolerance, blood pressure, potassium, and eGFR meet escalation criteria they will be given LCZ696 100 mg bid for three weeks. (If they do not meet escalation criteria they will be continued on LCZ696 50 mg bid.) After three weeks, they will return to the CRC for the next escalation visit. If they meet criteria for escalation they will be given LCZ 200 mg bid for ten days. (If they do not meet escalation criteria they will be continued on the highest tolerated dose).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: LCZ 696
Description: Treatment with LCZ696 is unblinded in this study. After the two acute study days, subjects will be provided LCZ696 50 mg bid for two weeks. At the end of those two weeks subjects will report to the Clinical Research Center (CRC) for a dose escalation visit. If their tolerance, blood pressure, potassium, and eGFR meet escalation criteria they will be given LCZ696 100 mg bid for three weeks. (If they do not meet escalation criteria they will be continued on LCZ696 50 mg bid.) After three weeks, they will return to the CRC for the next escalation visit. If they meet criteria for escalation they will be given LCZ 200 mg bid for ten days. (If they do not meet escalation criteria they will be continued on the highest tolerated dose).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: LCZ 696
Description: Treatment with LCZ696 is unblinded in this study. After the two acute study days, subjects will be provided LCZ696 50 mg bid for two weeks. At the end of those two weeks subjects will report to the Clinical Research Center (CRC) for a dose escalation visit. If their tolerance, blood pressure, potassium, and eGFR meet escalation criteria they will be given LCZ696 100 mg bid for three weeks. (If they do not meet escalation criteria they will be continued on LCZ696 50 mg bid.) After three weeks, they will return to the CRC for the next escalation visit. If they meet criteria for escalation they will be given LCZ 200 mg bid for ten days. (If they do not meet escalation criteria they will be continued on the highest tolerated dose).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Placebo
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Para-aminohippurate
Description: Para-aminohippurate (PAH) will be given at a dose of 8 mg/kg loading dose followed by a 12 mg/min steady-state infusion during each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Para-aminohippurate
Description: Para-aminohippurate (PAH) will be given at a dose of 8 mg/kg loading dose followed by a 12 mg/min steady-state infusion during each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Para-aminohippurate
Description: Para-aminohippurate (PAH) will be given at a dose of 8 mg/kg loading dose followed by a 12 mg/min steady-state infusion during each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Para-aminohippurate
Description: Para-aminohippurate (PAH) will be given at a dose of 8 mg/kg loading dose followed by a 12 mg/min steady-state infusion during each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Iohexol
Description: Iohexol will be given as 5 mL of iohexol solution (3.235 g iohexol) intravenously on each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Iohexol
Description: Iohexol will be given as 5 mL of iohexol solution (3.235 g iohexol) intravenously on each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Iohexol
Description: Iohexol will be given as 5 mL of iohexol solution (3.235 g iohexol) intravenously on each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Iohexol
Description: Iohexol will be given as 5 mL of iohexol solution (3.235 g iohexol) intravenously on each study day.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Aprepitant
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Aprepitant
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Aprepitant
Description: Placebo or aprepitant 120 mg will be given orally on study days 1 and 2 and again on study days 3 and 4