Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C] MK-5475, Frespaciguat
MK-5475 · 5 trials · 5 indications
6MWD is assessed using the 6-minute walk test (6MWT).
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.
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.
Amount of \[14C\]MK-5475 and its metabolites excreted in urine (Aeu) derived from urine collections at each sampling interval.
Cumulative amount of \[14C\] MK-5475 and its metabolites excreted in urine derived from urine collections at each sampling interval
Percentage of \[14C\]MK-5475 and its metabolites excreted in urine derived from urine collections at each sampling interval.
Cumulative percentage of \[14C\]MK-5475 and its metabolites excreted in urine derived from urine collections at each sampling interval.
Amount of \[14C\]MK-5475 and its metabolites excreted in feces derived from feces collections at each sampling interval.
Cumulative amount of \[14C\]MK-5475 and its metabolites excreted in feces derived from feces collections at each sampling interval.
Cumulative percentage of \[14C\]MK-5475 and its metabolites excreted in feces derived from feces collections at each sampling interval.
Area under concentration time curve (AUC) from time zero to the last quantifiable concentration derived from the whole blood and plasma concentration-time profiles following IV administration of \[14C\]MK-5475.
AUC from time zero extrapolated to infinity derived from the whole blood and plasma concentration-time profiles following IV administration of \[14C\]MK-5475.
Cmax is the measure of the maximum amount of \[14C\]MK-5475 in the plasma after the dose is given.
T1/2 is the time required for \[14C\]MK-5475 concentration in the plasma to decrease by 50%.
Tmax is a measure of the time to reach the maximum concentration in the plasma after the \[14C\]MK-5475 dose.
CL is defined as apparent total clearance of \[14C\]MK-5475 from plasma after IV administration
Vz is defined as apparent volume of distribution of \[14C\]MK-5475 during terminal phase after IV administration.
AUC time zero to infinity (0-∞) of \[14C\]MK-5475 in plasma/AUC0-∞ of total radioactivity in plasma.
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. 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 percentage of participants who experienced an AE was assessed.
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. 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.
PVR was calculated in participants after MK-5475 dosing at baseline and Day 28. Based on the variables obtained by right heart catheterization (RHC), the fold change from baseline individual PVR was calculated. The difference from baseline was assessed on the log scale and then back-transformed for reporting (percent change from baseline). Per protocol, this outcome measure was only assessed during the Part 2 and was not assessed during part 1.
An AE was defined as any untoward medical occurrence in a participant which may not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that was temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The number of participants who experienced at least 1 AE was reported by dose separately for Part 1 plus Part 2 Period 1, for the RHC Period, and for the FRI Period.
An AE was defined as any untoward medical occurrence in a participant which may not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that was temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The number of participants who discontinued from the study due to an AE was reported by dose separately for Part 1 plus Part 2 Period 1, for the RHC Period, and for the FRI Period.
For each participant in the RHC Period, the percentage change from baseline for the minimum post-dose PVR value over the duration of the RHC procedure was calculated. The average of pre-dose measurements was set as the baseline. Mean (SD) percent change from baseline in PVR minimum were calculated and reported for each dose group that underwent RHC in Part 2. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
| Arm | Type | Description |
|---|---|---|
| Frespaciguat | EXPERIMENTAL | Participants with PH-COPD will receive 380 µg of frespaciguat as an oral inhalation once daily for 24 weeks (base period) and thereafter for up to 42 months (optional extension period). |
| Placebo | PLACEBO_COMPARATOR | Participants with PH-COPD will receive matching placebo as an oral inhalation once daily for 24 weeks (base period) and then 380 µg of frespaciguat as an oral inhalation once daily for up to 42 months (optional extension period). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
| [14C] MK-5475 | EXPERIMENTAL | \[14C\] MK-5475 is administered as single IV bolus dose of 100μg on Day 1. |
| Part 1: Frespaciguat | EXPERIMENTAL | Participants receive frespaciguat 360 μg once daily (QD) via inhalation from Days 1-7. Following review of pharmacokinetic (PK) and safety data, a second 7 days of dosing may be initiated. A dose of up to 360 μg up to twice a day may be administered based on PK data in these participants. |
| Part 1: Placebo | PLACEBO_COMPARATOR | Participants receive placebo QD via inhalation from Days 1-7. |
| Part 2: Frespaciguat | EXPERIMENTAL | Participants receive frespaciguat 32 µg, 100 µg, 195 µg or 380 μg QD via inhalation from Days 1-28. |
| Part 2: Placebo | PLACEBO_COMPARATOR | Participants receive placebo QD via inhalation from Days 1-28. |
| Panel A: Frespaciguat 120 ug/165 ug/240 ug/240 ug/240 ug (Parts 1 and 2) | EXPERIMENTAL | Participants in Panel A will receive a single inhaled dose of frespaciguat 120 ug in Period 1 of Part 1, followed by frespaciguat 165 ug in Period 2, followed by frespaciguat 240 ug in Period 3. Each dose will be separated by at least a 7-day washout. In Part 2 Period 2, participants will receive a single inhaled dose of frespaciguat 240 ug and undergo a right heart catheterization (RHC). In Part 2 Period 3, participants will receive a single inhaled dose of frespaciguat 240 ug and undergo a functional respiratory imaging (FRI). |
| Panel B: 300 ug/360 ug/360 ug (Part 2) | EXPERIMENTAL | Participants in Panel B will receive a single inhaled dose of frespaciguat 300 ug in Period 1 of Part 2. In Period 2 of Part 2, participants will receive a single inhaled dose of frespaciguat 360 ug and undergo FRI. In Period 3 of Part 2, participants receive a single inhaled dose of frespaciguat 360 ug and undergo RHC. Each dose will be separated by at least a 7-day washout. |
| Panel C: 300 ug/360 ug/360 ug (Part 2, Expansion) | EXPERIMENTAL | Participants in Panel C will receive a single inhaled dose of frespaciguat 300 ug in Period 1 of Part 2. In Period 2 of Part 2, participants will receive a single inhaled dose of frespaciguat 360 ug and undergo FRI. In Period 3 of Part 2, participants receive a single inhaled dose of frespaciguat 360 ug and undergo RHC. Each dose will be separated by at least a 7-day washout. |
| Panel D: 480 ug/120 ug/120 ug (Part 2) | EXPERIMENTAL | Participants in Panel D will receive a single inhaled dose of frespaciguat 480 ug in Period 1 of Part 2. In Period 2 of Part 2, participants will receive a single inhaled dose of frespaciguat 120 ug and undergo FRI. In Period 3 of Part 2, participants receive a single inhaled dose of frespaciguat 120 ug and undergo RHC. Each dose will be separated by at least a 7-day washout. |
| Placebo (Part 1) | PLACEBO_COMPARATOR | Participants will receive a single inhaled dose of matching placebo in Part 1. |
| Name | Type | Description |
|---|---|---|
| Frespaciguat | DRUG | Frespaciguat 380 µg administered as dry powder inhalation once daily. |
| Placebo | DRUG | Placebo administered as dry powder inhalation once daily. |
| Placebo to Frespaciguat | DRUG | Placebo administered as dry powder inhalation |
| [14C] MK-5475 | DRUG | \[14C\] MK-5475 is administered as a single IV bolus dose in healthy male participants on Day 1. |
The key inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Has Group 3.1 pulmonary hypertension chronic obstructive pulmonary disease (PH-COPD) as defined by the Clinical Classification of Pulmonary Hypertension. * Has a right heart catheterization...
MK-5475 is an investigational small molecule being developed by Merck & Company, Inc. (ticker MRK). It is in Phase 1 clinical development, and its specific therapeutic indications have not been disclosed. The compound has been studied in a single completed Phase 1 trial involving healthy male participants.
MK-5475 is being developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is the sponsor of the clinical program for this investigational small molecule.
MK-5475 is in Phase 1 clinical development. One Phase 1 trial has been completed, and no active trials are currently listed. The drug remains investigational and has not been approved by the FDA for any indication.
MK-5475 has been evaluated in one completed Phase 1 trial, NCT06777602, titled a study to understand how radiolabeled MK-5475 is taken up, broken down, and removed from the body in healthy participants. The trial enrolled 8 healthy male volunteers in the United States and was uncontrolled.
Yes, [14C] MK-5475 is an alternative name for MK-5475. The [14C] label refers to the carbon-14 radiolabeled form of the compound used in the completed Phase 1 trial NCT06777602 to study its absorption, metabolism, and excretion in healthy participants.