A Study of the Efficacy and Safety of Frespaciguat (MK-54... | NCT04732221 | Trialant
NCT04732221
Sponsor
Merck Sharp & Dohme LLC
Status
Completed
Last Update Posted
May 25, 2025Actual
Enrollment
168Actual
Phase
Phase 2Phase 3
Conditions
Pulmonary Arterial Hypertension
Hypertension, Pulmonary
Interventions
Frespaciguat
Placebo to Frespaciguat
Countries
United States
Argentina
Australia
Belgium
Canada
Colombia
France
Germany
Greece
Israel
Italy
Mexico
New Zealand
Poland
Russia
Sweden
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT04732221
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
5475-007
Secondary IDs
ID
Type
Description
Link
MK-5475-007
Other Identifier
MSD
2022-500877-15-00
Registry Identifier
EU CT
U1111-1278-4977
Registry Identifier
UTN
2020-001108-40
EudraCT Number
Brief Title
A Study of the Efficacy and Safety of Frespaciguat (MK-5475) in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)
Official Title
A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of MK-5475 in Adults With Pulmonary Arterial Hypertension
Acronym
Not provided
Organization
Merck Sharp & Dohme LLCINDUSTRY
Status Module
Record Verification Date
May 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 19, 2021Actual
Primary Completion Date
Jan 4, 2024Actual
Completion Date
Jul 2, 2024Actual
First Submitted Date
Jan 27, 2021
First Submission Date that Met QC Criteria
Jan 27, 2021
First Posted Date
Feb 1, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Dec 20, 2024
Results First Submitted that Met QC Criteria
Feb 3, 2025
Results First Posted Date
Feb 21, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 9, 2025
Last Update Posted Date
May 25, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Merck Sharp & Dohme LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a two-part (Phase 2/Phase 3) study of frespaciguat, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH).
The first part (Phase 2) will assess three different doses of frespaciguat compared to placebo in a base period of 12 weeks, followed by comparison of three different doses of frespaciguat during an optional 40 month extension period. The treatment dose with the best efficacy and safety profile in the phase 2 cohort base period will be selected for use in the second part (Phase 3) of the study. The primary hypothesis of Phase 2 is that at least one frespaciguat dose is superior to placebo in reducing pulmonary vascular resistance (PVR) from baseline at week 12.
The purpose of the second part (Phase 3) of the study is to confirm the efficacy, safety, and tolerability of frespaciguat at the selected dose compared to placebo during a 12 week base period followed by an extension period of up to 5 years. The primary hypothesis of Phase 3 is that frespaciguat is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12. Due to sponsor's decision this phase/part was not conducted.
Detailed Description
Not provided
Conditions Module
Conditions
Pulmonary Arterial Hypertension
Hypertension, Pulmonary
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
168Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Phase 2 Cohort Frespaciguat 380 µg
Experimental
Participants receive frespaciguat 380 µg via oral inhalation once daily for 12 week base period and for optional 40 month extension period.
Drug: Frespaciguat
Phase 2 Cohort Frespaciguat 100 µg
Experimental
Participants receive frespaciguat 100 µg via oral inhalation once daily for 12 week base period and for optional 40 month extension period.
Drug: Frespaciguat
Phase 2 Cohort Frespaciguat 32 µg
Experimental
Participants receive frespaciguat 32 µg via oral inhalation once daily for 12 week base period and for optional 40 month extension period.
Drug: Frespaciguat
Phase 2 Cohort Placebo
Placebo Comparator
Participants receive placebo via oral inhalation once daily for 12 week base period, and one of the MK-5475 doses (380, 100, or 32 µg) for the optional 40 month extension period.
Drug: Placebo to Frespaciguat
Phase 3 Cohort Frespaciguat
Experimental
Participants receive one of 3 frespaciguat doses (380, 100 or 32 µg) to be selected at end of the Phase 2 Cohort, administered via oral inhalation once daily for 12-week base period and up to 40 months in the extension period
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Frespaciguat
Drug
Frespaciguat (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
Phase 2 Cohort Frespaciguat 100 µg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks
PVR was calculated in participants after MK-5475 dosing at baseline and Week 12. PVR is assessed by right heart catheterization (RHC). Based on the variables obtained by right heart catheterization (RHC), the percentage change from baseline PVR was calculated. Per protocol, this outcome measure was assessed only for base period and was not assessed during extension period.
At baseline and 12 weeks
Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in excercise capacity. Each participant's 6MWD is to be measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
At baseline and 12 weeks
Secondary Outcomes
Measure
Description
Time Frame
Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD was measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Pulmonary arterial hypertension (PAH) in one of the following groups:
Idiopathic PAH
Heritable PAH
Drug and toxin-induced PAH
PAH associated with connective tissue disease, HIV infection, or congenital heart disease.
Diagnosis of PAH documented by right heart catheterization (RHC).
Eligibility RHC meeting all of the following criteria:
Mean pulmonary artery pressure (mPAP) ≥25 mmHg
Pulmonary vascular resistance (PVR) of ≥3 Wood units
Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤15 mmHg.
World Health Organization functional class (WHO-FC) symptoms between Class II and IV.
Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one at screening and one at randomization.
Body Mass Index (BMI) between 18.5 kg/m² and 40 kg/m² .
Agree to be abstinent from heterosexual intercourse or use contraception during the intervention period and for at least 14 days after the last dose of study intervention.
Female participants may not be pregnant or breastfeeding.
Exclusion Criteria:
Group 2 to 5 pulmonary hypertension.
PAH in one of the following groups:
Long term responders to calcium channel blockers
Overt features of venous/capillary involvement
Evidence of more-than-mild obstructive lung disease.
Evidence of more-than-mild parenchymal lung disease.
Evidence of more-than-mild obstructive sleep apnea (OSA) that is untreated.
Evidence or history of left heart disease, including any of the following:
Left ventricular ejection fraction (LVEF) ≤45%
Moderate or severe left-sided valvular disease (aortic or mitral valve stenosis or regurgitation)
Significant left ventricular diastolic dysfunction on echocardiographic evaluation
Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction: BMI>30 kg/m², essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease.
Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities.
Current smoker or currently uses electronic cigarettes (vapes).
History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated, with appropriate follow up, and unlikely to recur for the duration of the study.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
75 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Medical Director
Merck Sharp & Dohme LLC
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of California San Diego Health-Pulmonary Critical Care ( Site 0061)
Humbert M, Hassoun PM, Chin KM, Bortman G, Patel MJ, La Rosa C, Fu W, Loureiro MJ, Hoeper MM. MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study. Eur Respir J. 2024 Nov 14;64(5):2401110. doi: 10.1183/13993003.01110-2024. Print 2024 Nov.
The study was planned to be conducted in 2 parts: a Phase 2 dose selection cohort and a Phase 3 confirmatory cohort. Due to sponsor's decision, Phase 3 was not conducted.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
FG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
Periods
Title
Milestones
Reasons Not Completed
Base Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Nov 7, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
A total of approximately 450 participants will be randomized in this operationally seamless adaptive Phase 2/3 study. Phase 2 of the study will randomize approximately 164 participants into 4 arms, and Phase 3 of the study will randomize approximately 286 participants into 2 arms.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantInvestigatorOutcomes Assessor
Drug: Frespaciguat
Phase 3 Cohort Placebo
Placebo Comparator
Participants receive placebo via oral inhalation once daily for 12 week base period and up to 40 months in the extension period.
Drug: Placebo to Frespaciguat
Phase 2 Cohort Frespaciguat 32 µg
Phase 2 Cohort Frespaciguat 380 µg
Phase 3 Cohort Frespaciguat
Placebo to Frespaciguat
Drug
Placebo administered as dry powder inhalation
Phase 2 Cohort Placebo
Phase 3 Cohort Placebo
At baseline and 12 weeks
Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks
mRAP is the blood pressure in the right atrium of the heart. mRAP was assessed by right heart catheterization (RHC).A decrease in mRAP indicates improvement in right ventricular function, reduction of PAH related morbidity.
At baseline and 12 weeks
Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks
The cardiac index (CI) is a hemodynamic measure that represents the cardiac output (CO) of an individual divided by their body surface area (BSA). Cardiac index is assessed by right heart catheterization (RHC). An increase in CI is indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.
At baseline and 12 weeks
Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks
The stroke volume index represents the amount of blood in mL, per square meter of body surface area, that is mobilized with each heart beat. SVI is assessed by RHC. An increase in SVI indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.
At baseline and 12 weeks
Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD is to be measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
At baseline and 24 weeks
Phase 3 Cohort: Proportion of Participants Whose World Health Organization Functional Class (WHO-FC) is Not Worse at 12 Week Relative to Baseline
The World Health Organization (WHO) classification of functional status is a measure of disease severity, based on a patient's description of their level of functioning and symptoms of disease in relation to their everyday activity. Patients were to be assigned 1 of 4 WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity were to increase.
At baseline and 12 weeks
Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 2.25 years
Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Up to approximately 2.25 years
Phase 3 Cohort: Number of Participants Who Experienced an Adverse Event
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 2.25 years
Phase 3 Cohort: Number of Participants Who Discontinued Study Drug Due to an AE
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Up to approximately 2.25 years
University of California Davis Health-Internal Medicine: Pulmonary, Critical Care and Sleep Medicine
Sacramento
California
95817
United States
UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0063)
San Francisco
California
94143
United States
University of Colorado - Denver ( Site 0003)
Aurora
Colorado
80045
United States
Cardiovascular Institute of North Colorado - Banner Health ( Site 0013)
Greeley
Colorado
80631
United States
Georgetown University Hospital ( Site 0025)
Washington D.C.
District of Columbia
20007
United States
University of Miami Hospital-Division of Pulmonary & Critical Care ( Site 0053)
Miami
Florida
33136
United States
AdventHealth Orlando ( Site 0040)
Orlando
Florida
32803
United States
Tampa General Hospital ( Site 0058)
Tampa
Florida
33606
United States
Indiana University Health Methodist Hospital ( Site 0045)
Indianapolis
Indiana
46202-1239
United States
University of Iowa Hospital and Clinics ( Site 0009)
Iowa City
Iowa
52242
United States
University of Kansas Medical Center ( Site 0038)
Kansas City
Kansas
66160
United States
University of Kentucky ( Site 0006)
Lexington
Kentucky
40536
United States
Norton Pulmonary Specialists ( Site 0048)
Louisville
Kentucky
40202
United States
University of Maryland ( Site 0032)
Baltimore
Maryland
21201
United States
Washington University School of Medicine ( Site 0066)
St Louis
Missouri
63110
United States
University of Nebraska Medical Center ( Site 0041)
Omaha
Nebraska
68198
United States
University of New Mexico, Health Sciences Center ( Site 0028)
Albuquerque
New Mexico
87131
United States
Clinical Trials Unit at Eastowne Medical Office Building ( Site 0019)
Chapel Hill
North Carolina
27514
United States
AnMed Health ( Site 0033)
Anderson
South Carolina
29621
United States
Statcare Pulmonary Consultants ( Site 0067)
Knoxville
Tennessee
37934
United States
University of Texas Southwestern Medical Center at Dallas ( Site 0012)
Dallas
Texas
75390
United States
Houston Methodist Research Institute ( Site 0036)
Houston
Texas
77030
United States
The University of Texas Health Science Center at Houston ( Site 0054)
Houston
Texas
77030
United States
Sentara Norfolk General Hospital ( Site 0014)
Norfolk
Virginia
23507
United States
West Virginia University-WVU Heart and Vascular Institute ( Site 0051)
Morgantown
West Virginia
26506
United States
Cardiologia Palermo ( Site 0140)
Ciudad Autonoma de Buenos Aires
Buenos Aires
C1425BNG
Argentina
Centro Medico Capital ( Site 0131)
La Plata
Buenos Aires
B1904AAW
Argentina
Hospital Universitario Austral ( Site 0138)
Pilar
Buenos Aires
B1629ODT
Argentina
Instituto de Investigaciones Clinicas Quilmes ( Site 0141)
Quilmes
Buenos Aires
B1878GEG
Argentina
Hospital El Cruce Nestor Carlos Kirchner ( Site 0132)
San Juan Bautista
Buenos Aires
1888
Argentina
Sanatorio de la Trinidad Mitre ( Site 0130)
Buenos Aires
Buenos Aires F.D.
1039
Argentina
Instituto Cardiovascular de Rosario ( Site 0128)
Rosario
Santa Fe Province
S2000DSR
Argentina
Hospital Privado Universitario de Córdoba ( Site 0137)
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
FG003
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
FG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
FG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
FG006
Extension Period: MK-5475 380 μg
Participants who received MK-3475 380 ug in the base period, and participants who received placebo in the base period and were randomized to the 380 ug group in the extension period, were administered MK-3475 380 ug via oral inhalation for up to 25 months
FG00041 subjects
FG00142 subjects
FG00244 subjects
FG00341 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG00039 subjects
FG00141 subjects
FG00243 subjects
FG00341 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Death
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Extension Period
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00445 subjects
FG00546 subjects
FG00644 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
BG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
BG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
BG003
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00041
BG00142
BG00244
BG00341
BG004168
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00052.1± 12.7
BG00148.1± 16.9
BG00251.7± 14.2
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00028
BG00134
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00011
BG00114
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0003
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks
PVR was calculated in participants after MK-5475 dosing at baseline and Week 12. PVR is assessed by right heart catheterization (RHC). Based on the variables obtained by right heart catheterization (RHC), the percentage change from baseline PVR was calculated. Per protocol, this outcome measure was assessed only for base period and was not assessed during extension period.
All randomized participants who received ≥1 dose of study treatment and had baseline observation.
Posted
Least Squares Mean
Standard Error
Percentage Change
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
Units
Counts
Participants
OG00041
OG00142
OG00244
OG003
Title
Denominators
Categories
Title
Measurements
OG0004.3± 4.45
OG001-4.9± 4.07
OG002-17.6± 4.07
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Robust Regression
Missing data at week 12 due to death were imputed using the worst observed value and other missingness were imputed using J2R method
0.068
A 1-sided p-value was obtained from fitting a Robust regression estimate based on a Huber-type M estimator including terms for treatment and WHO-FC (Class II and Class III/IV) at baseline
Treatment difference
-9.2
2-Sided
95
-21.3
2.9
Least Square Mean of the overall treatment difference with 95% confidence interval (CI) was reported
Superiority
Primary
Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in excercise capacity. Each participant's 6MWD is to be measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Posted
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Secondary
Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD was measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
Posted
Mean
Standard Deviation
Meters
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Secondary
Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks
mRAP is the blood pressure in the right atrium of the heart. mRAP was assessed by right heart catheterization (RHC).A decrease in mRAP indicates improvement in right ventricular function, reduction of PAH related morbidity.
All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
Posted
Mean
Full Range
Millimeters of Mercury (mmHg)
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
Secondary
Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks
The cardiac index (CI) is a hemodynamic measure that represents the cardiac output (CO) of an individual divided by their body surface area (BSA). Cardiac index is assessed by right heart catheterization (RHC). An increase in CI is indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.
All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
Posted
Mean
Full Range
Liter/minutes/meter square (L/min/m^2)
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Base Period: MK-5475 380 µg
Secondary
Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks
The stroke volume index represents the amount of blood in mL, per square meter of body surface area, that is mobilized with each heart beat. SVI is assessed by RHC. An increase in SVI indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.
All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
Posted
Mean
Full Range
mL/beat/m^2
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Base Period: MK-5475 380 µg
Secondary
Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD is to be measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Posted
At baseline and 24 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Secondary
Phase 3 Cohort: Proportion of Participants Whose World Health Organization Functional Class (WHO-FC) is Not Worse at 12 Week Relative to Baseline
The World Health Organization (WHO) classification of functional status is a measure of disease severity, based on a patient's description of their level of functioning and symptoms of disease in relation to their everyday activity. Patients were to be assigned 1 of 4 WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity were to increase.
Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Posted
At baseline and 12 weeks
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG003
Secondary
Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Analysis population consisted of all randomized participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to approximately 2.25 years
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Secondary
Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Analysis population consisted of all randomized participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to approximately 2.25 years
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
Secondary
Phase 3 Cohort: Number of Participants Who Experienced an Adverse Event
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Posted
Up to approximately 2.25 years
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
OG003
Base Period: MK-5475 380 µg
Secondary
Phase 3 Cohort: Number of Participants Who Discontinued Study Drug Due to an AE
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Posted
Up to approximately 2.25 years
ID
Title
Description
OG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
OG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
OG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
Time Frame
Up to approximately 37 months
Description
All-cause mortality includes all randomized participants and adverse events include all participants who received at least one dose of study treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Base Period: Placebo
Participants received placebo via oral inhalation once daily for 12 week base period
2
41
5
41
18
41
EG001
Base Period: MK-5475 32 µg
Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period
0
42
4
42
22
42
EG002
Base Period: MK-5475 100 µg
Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period
1
44
3
44
23
44
EG003
Base Period: MK-5475 380 µg
Participants received MK-5475 380 µg via oral inhalation once daily for 12 week base period
0
41
4
41
21
41
EG004
Extension Period: Placebo to MK-5475 32 µg
Participants who received placebo for the during the 12 week base period and were randomized to MK-3475 32 ug for the extension period, received MK-3475 32 ug via oral inhalation once daily for up to 25 months
1
11
3
11
7
11
EG005
Extension Period: Placebo to MK-5475 100 µg
Participants who received placebo for the during the 12 week base period and were randomized to MK-3475 100 ug for the extension period, received MK-3475 100 ug via oral inhalation once daily for up to 25 months
0
9
2
9
7
9
EG006
Extension Period: Placebo to MK-5475 380 µg
Participants who received placebo for the during the 12 week base period and were randomized to MK-3475 380 ug for the extension period, received MK-3475 380 ug via oral inhalation once daily for up to 25 months
0
10
4
10
8
10
EG007
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug during the 12 week base period, received MK-3475 32 ug via oral inhalation once daily for up to 25 months
0
34
5
34
24
34
EG008
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug during the 12 week base period, received MK-3475 100 ug via oral inhalation once daily for up to 25 months
0
37
4
37
28
37
EG009
Extension Period: MK-5475 380 μg
Participants who received MK-3475 380 ug during the 12 week base period, received MK-3475 380 ug via oral inhalation once daily for up to 25 months
2
34
11
34
28
34
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG0030 events0 affected41 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected9 at risk
EG0060 events0 affected10 at risk
EG0070 events0 affected34 at risk
EG0080 events0 affected37 at risk
EG0091 events1 affected34 at risk
Atrial flutter
Cardiac disorders
MedDRA 27.0
Systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Cardiac failure
Cardiac disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Ventricular tachycardia
Cardiac disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Catheter site haemorrhage
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Chest pain
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Complication associated with device
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0011 events1 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Multiple organ dysfunction syndrome
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Sudden death
General disorders
MedDRA 27.0
Systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Vascular device occlusion
General disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
COVID-19
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Device related sepsis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Encephalitis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Erysipelas
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0021 events1 affected44 at risk
EG003
Infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Lower respiratory tract infection viral
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0001 events1 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Pneumonia mycoplasmal
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Pneumonia viral
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Sepsis
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Vascular device infection
Infections and infestations
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Hypervolaemia
Metabolism and nutrition disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Systemic lupus erythematosus
Musculoskeletal and connective tissue disorders
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Adenocarcinoma of colon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Invasive ductal breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Lung neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0021 events1 affected44 at risk
EG003
Malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 27.0
Systematic Assessment
EG0000 events0 affected41 at risk
EG0010 events0 affected42 at risk
EG0020 events0 affected44 at risk
EG003
Vulvovaginal warts
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Point of Contact
Title
Organization
Phone
Extension
Email
Senior Vice President, Global Clinical Development
Missing data at week 12 due to death were imputed using the worst observed value and other missingness were imputed using J2R method
<0.001
based on a Huber-type M estimator including terms for treatment and WHO-FC (Class II and Class III/IV) at baseline
Treatment difference
-22.0
2-Sided
95
-33.7
-10.3
Least Square Mean of the overall treatment difference with 95% confidence interval (CI) was reported
Superiority
OG000
OG003
Robust Regression
Missing data at week 12 due to death were imputed using the worst observed value and other missingness were imputed using J2R method
0.002
A 1-sided p-value was obtained from fitting a Robust regression estimate based on a Huber-type M estimator including terms for treatment and WHO-FC (Class II and Class III/IV) at baseline
Treatment difference
-19.9
2-Sided
95
-33.4
-6.4
Least Square Mean of the overall treatment difference with 95% confidence interval (CI) was reported
Superiority
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-5475 32 μg in the base period, and those who received matching placebo for MK-5475 32 μg at the end of the base period (12 weeks) were administered MK-5475 32 μg via oral inhalation up to 25 months in the extension period
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
Units
Counts
Participants
OG00038
OG00141
OG00242
OG00340
Title
Denominators
Categories
Title
Measurements
OG00024.6± 66.3
OG00127.4± 53.1
OG00210.8± 45.6
OG00311.3± 38.9
Units
Counts
Participants
OG00036
OG00141
OG00241
OG00340
Title
Denominators
Categories
Title
Measurements
OG0000.3(-8.0 to 9.0)
OG0010.3(-17.0 to 7.0)
OG002-0.5(-8.0 to 14.0)
OG003-0.1(-14.0 to 12.0)
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
Units
Counts
Participants
OG00037
OG00140
OG00241
OG00341
Title
Denominators
Categories
Title
Measurements
OG0000.1(-0.9 to 3.1)
OG0010.0(-1.7 to 1.4)
OG0020.2(-1.4 to 1.5)
OG0030.1(-1.6 to 1.8)
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
Units
Counts
Participants
OG00037
OG00140
OG00241
OG00341
Title
Denominators
Categories
Title
Measurements
OG0002.9(-9.3 to 44.4)
OG0010.2(-37.2 to 20.7)
OG0023.2(-21.8 to 35.2)
OG0031.2(-29.1 to 25.1)
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
OG006
Extension Period: MK-5475 380 μg
Participants who received MK-3475 380 ug in the base period, and participants who received placebo in the base period and were randomized to the 380 ug group in the extension period, were administered MK-3475 380 ug via oral inhalation for up to 25 months
Units
Counts
Participants
OG00041
OG00142
OG00244
OG00341
OG00445
OG00544
OG00644
Title
Denominators
Categories
Title
Measurements
OG00027
OG00128
OG00228
OG00327
OG00433
OG00538
OG00639
OG003
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
OG006
Extension Period: MK-5475 380 μg
Participants who received MK-3475 380 ug in the base period, and participants who received placebo in the base period and were randomized to the 380 ug group in the extension period, were administered MK-3475 380 ug via oral inhalation for up to 25 months
Units
Counts
Participants
OG00041
OG00142
OG00244
OG00341
OG00445
OG00544
OG00644
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
OG0030
OG0040
OG0051
OG0060
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG003
Base Period: MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period
OG004
Extension Period: MK-5475 32 µg
Participants who received MK-3475 32 ug in the base period, and participants who received placebo in the base period and were randomized to the 32 ug group in the extension period, were administered MK-3475 32ug via oral inhalation for up to 25 months
OG005
Extension Period: MK-5475 100 µg
Participants who received MK-3475 100 ug in the base period, and participants who received placebo in the base period and were randomized to the 100 ug group in the extension period, were administered MK-3475 100 ug via oral inhalation for up to 25 months