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MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)

Primary Purpose

Coronavirus Disease 2019 (COVID-19), Pneumonia, Hypoxemia

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

MK-5475

Placebo

About this trial

This is an interventional treatment trial for Coronavirus Disease 2019 (COVID-19)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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 MK-5475 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Panel A MK-5475 180 µg

Panel A Placebo

Panel B MK-5475 360 µg

Panel B Placebo

Panel C MK-5475 ≤360 µg

Panel C Placebo

Arm Description

Participants receive 180 µg of MK-5475 once daily (QD) via inhalation from Days 1-7.

Participants receive MK-5475-matching placebo QD via inhalation from Days 1-7.

Participants receive 360 µg of MK-5475 QD via inhalation from Days 1-7.

Participants receive MK-5475-matching placebo QD via inhalation from Days 1-7.

Participants receive ≤360 µg of MK-5475 QD via inhalation from Days 1-7.

Participants receive MK-5475-matching placebo QD via inhalation from Days 1-7.

Outcomes

Primary Outcome Measures

Number of Participants Who Experience an Adverse Event (AE)

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)

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)

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)

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)

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)

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)

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)

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)

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

Full Information

NCT ID

NCT04425733

First Posted

June 8, 2020

Last Updated

August 12, 2020

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT04425733

Brief Title

MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)

Official Title

A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Business reasons

Study Start Date

July 7, 2020 (Anticipated)

Primary Completion Date

November 10, 2020 (Anticipated)

Study Completion Date

November 10, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of MK-5475 after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that MK-5475 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronavirus Disease 2019 (COVID-19), Pneumonia, Hypoxemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Panel A MK-5475 180 µg

Arm Type

Experimental

Arm Description

Participants receive 180 µg of MK-5475 once daily (QD) via inhalation from Days 1-7.

Arm Title

Panel A Placebo

Arm Type

Placebo Comparator

Arm Description

Participants receive MK-5475-matching placebo QD via inhalation from Days 1-7.

Arm Title

Panel B MK-5475 360 µg

Arm Type

Experimental

Arm Description

Participants receive 360 µg of MK-5475 QD via inhalation from Days 1-7.

Arm Title

Panel B Placebo

Arm Type

Placebo Comparator

Arm Description

Participants receive MK-5475-matching placebo QD via inhalation from Days 1-7.

Arm Title

Panel C MK-5475 ≤360 µg

Arm Type

Experimental

Arm Description

Participants receive ≤360 µg of MK-5475 QD via inhalation from Days 1-7.

Arm Title

Panel C Placebo

Arm Type

Placebo Comparator

Arm Description

Participants receive MK-5475-matching placebo QD via inhalation from Days 1-7.

Intervention Type

Drug

Intervention Name(s)

MK-5475

Intervention Description

MK-5475 administered at a dose of 180 µg or ≤360 µg QD via inhalation

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

MK-5475-matching placebo administered QD via inhalation

Primary Outcome Measure Information:

Title

Number of Participants Who Experience an Adverse Event (AE)

Description

Time Frame

Up to ~Day 21

Title

Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Description

Time Frame

Up to ~Day 7

Title

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)

Description

Time Frame

Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Title

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)

Description

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.

Time Frame

Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Title

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)

Description

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.

Time Frame

Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Title

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)

Description

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.

Time Frame

Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Title

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)

Description

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.

Time Frame

Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Title

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)

Description

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.

Time Frame

Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

Title

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)

Description

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.

Time Frame

Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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 MK-5475 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Learn more about this trial

MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)

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