Frespaciguat (MK-5475) in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)
- Conditions
- Coronavirus Disease 2019 (COVID-19)PneumoniaHypoxemia
- Interventions
- Drug: FrespaciguatDrug: Placebo
- Registration Number
- NCT04425733
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of frespaciguat after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that frespaciguat when administered to participants with COVID-19 pneumonia and hypoxemia improves arterial oxygenation as measured by the ratio of blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio) compared to placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Has virologically confirmed COVID-19 requiring hospital admission.
- Has respiratory symptoms including cough and dyspnea
- Requires supplemental oxygen therapy
- Male participant is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) (example, 5 terminal half-lives after the last dose of study intervention)
- Female participant is not a woman of childbearing potential (WOCBP) or is a WOCBP who is abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) (example, 5 terminal half-lives after the last dose of study intervention)
- Has pre-existing medical conditions of any nature which are immediately pre-terminal such as death or limitation of life-sustaining therapy is expected to be imminent
- Requires or is expected to require invasive mechanical ventilation
- Requires or is expected to require noninvasive mechanical ventilation
- Has any issue which would prohibit them from effective use of the frespaciguat inhaler
- Hypoxemia which is explained by any condition other than COVID-19, example, preexisting cardiac or pulmonary disease
- Has severe hepatic impairment (meets Child-Pugh Class C criteria)
- Has severe renal impairment and/or requirement for renal dialysis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Panel A Frespaciguat 180 µg Frespaciguat Participants receive 180 µg of frespaciguat once daily (QD) via inhalation from Days 1-7. Panel A Placebo Placebo Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7. Panel B Frespaciguat 360 µg Frespaciguat Participants receive 360 µg of frespaciguat QD via inhalation from Days 1-7. Panel B Placebo Placebo Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7. Panel C Frespaciguat ≤360 µg Frespaciguat Participants receive ≤360 µg of frespaciguat QD via inhalation from Days 1-7. Panel C Placebo Placebo Participants receive frespaciguat-matching placebo QD via inhalation from Days 1-7.
- Primary Outcome Measures
Name Time Method Number of Participants Who Experience an Adverse Event (AE) Up to ~Day 21 An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) Up to ~Day 7 An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.
Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.
Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.
Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.
Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.
Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.
Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.
Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2) Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose) The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.
- Secondary Outcome Measures
Name Time Method