Pulmonary Arterial HypertensionPhase 1NCT03744637

A Study of Single Doses of Frespaciguat (MK-5475) on Pulmonary Vascular Resistance (MK-5475-002)

A Phase 1 study testing Frespaciguat in people with Pulmonary Arterial Hypertension, run by Merck Sharp & Dohme LLC at 1 site in Moldova.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study of frespaciguat in participants with Group 1 pulmonary arterial hypertension (PAH) will assess the safety, tolerability and pharmacokinetics (PK) of inhaled frespaciguat. There is no formal hypothesis to be tested. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: Frespaciguat
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 25 participants
Where: 1 siteMoldova
Study dates: 18 Jan 2019to 11 Dec 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Be or have suspected Group 1 pulmonary hypertension as defined by the Nice 2013 Clinical Classification, including: idiopathic PAH, heritable PAH, drug- or toxin-induced PAH, or PAH associated with connective tissue disease or congenital heart disease
Have a Body Mass Index (BMI) ≤35 kg/m2,
Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is a woman of nonchildbearing potential (WONCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) after the last dose of study intervention: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception unless confirmed to be azoospermic (Vasectomized) or secondary to medical cause.
Have a clinical indication for right heart catheterization (RHC) as part of initial work-up or ongoing medical management
Panel A: Have history of RHC within 3 years of starting study medication demonstrating mean pulmonary artery pressure of ≥ 27 mmHg and pulmonary vascular resistance (PVR) of ≥ 300 dynes/sec/cm5
Panels B/C/D: Have history of RHC within 3 years of starting study medication demonstrating mean pulmonary artery pressure of ≥ 27 mmHg and PVR of ≥ 300 dynes/sec/cm5 OR have an echocardiogram performed by the investigator at screening or within 1 year of screening demonstrating pulmonary artery systolic pressure ≥ 50 mmHg in conjunction with 1 or more of the following: tricuspid regurgitation velocity > 3.0 m/s and or significant right heart enlargement and or reduced right heart function.

Who cannot join

Has pulmonary hypertension subtypes including the following according to Nice 2013 Clinical Classification: human immunodeficiency (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, pulmonary veno-occlusive disease (PVOD) and or pulmonary capillary hemangiomatosis (PCH), persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension owing to left heart diseases, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, valvular disease, congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies, pulmonary hypertension owing to lung diseases and/or hypoxia, Chronic obstructive pulmonary disease, Interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental abnormalities, pulmonary hypertension defined as chronic thromboembolic pulmonary hypertension [CTEPH]), pulmonary hypertension with unclear multifactorial mechanisms, hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy, systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis, metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders, others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental pulmonary hypertension
Has a history of clinically significant endocrine (not including stable diabetes mellitus), gastrointestinal, cardiovascular, hematological, hepatic (not including chronic stable Hepatitis B and Hepatitis C), immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
Is mentally or legally incapacitated, has significant emotional problems
History of cancer (malignancy) except nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated 10 years prior to screening
History of significant multiple and/or severe allergies
Known hypersensitivity to iodine or iodine containing products

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Positive for HIV
Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks of screening
Has persistent or permanent atrial fibrillation with an uncontrolled ventricular rate
Has significantly impaired gas exchange
Has an active respiratory infection (e.g. common cold, bronchitis, influenza, pneumonia) with lung function outside of the normal range
Is currently on monotherapy calcium channel blockers as a specific treatment for pulmonary hypertension
Has taken nitrates within 24 hours of anticipated dosing
Has taken inhaled prostacyclin within 24 hours of anticipated dosing (iloprost or treprostinil)
Has taken diltiazem immediate release taken within 24 hours or extended release taken within 48 hours of anticipated dosing
Has taken sildenafil or vardenafil within 24 hours or tadalafil within 7 days of anticipated dosing
Has taken soluble guanylate cyclase (sGC) activator for PAH within 24 hours of anticipated dosing
Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit
Has participated in another investigational study within 4 weeks
Does not agree to follow the smoking restrictions
Part 2 only: Suffers from claustrophobia and would be unable to undergo computerized tomography (CT) scan
Part 2 only: Has participated in a positron-emission tomography (PET) research study or other study involving administration of a radioactive substance or ionizing radiation within 12 months prior to the screening visit, or has undergone or plans to have extensive radiological examination within this period
Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day
Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months. Participants must have a negative urine drug screen (UDS) prior to randomization

Trial locations and contacts

1 site in 1 country.

Moldova1 site

Republican Clinical Hospital of Moldova ( Site 0001)
Chisinau, 2025

Other trials in Moldova

About this study

Official title: A Study to Assess the Effect of Single Doses of MK-5475 on Pulmonary Vascular Resistance in Patients With Moderate to Severe Pulmonary Arterial Hypertension

Read the detailed description

In Part 1, one panel (Panel A) of up to 8 participants will dose in up to 3 dosing periods, with a minimum washout of 7 days between dosing periods. In each dosing period, 6 participants will receive frespaciguat and 2 will receive placebo, with 2 different participants receiving placebo in each of the dosing periods. Review of available safety data will occur prior to escalating to the next dose level.

Participants from Part 1 may continue into Part 2, which will assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose inhaled frespaciguat. Three additional panels of participants (Panels B, C and D) will be enrolled into Part 2. Participants in Panel A will participate in 2 open-label dosing periods to assess PD measures associated with right heart catherization (RHC) [Period 2] and functional respiratory imaging (FRI) [Period 3]. Participants in Panels B, C, and D will participate in 3 dosing periods: Period 1 (open-label assessment of safety/tolerability and PK), Period 2 (FRI period) and Period 3 (RHC period).

Conditions: Pulmonary Arterial Hypertension
Being tested: Frespaciguat, Placebo
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FrespaciguatDrug
Also called MK-5475
Single inhaled dose of frespaciguat 120, 165, 240, 300, 360, or 480 ug depending upon randomization
PlaceboDrug
Single inhaled dose of placebo to match frespaciguat

Study groups in NCT03744637
Study group	Role	What they receive
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). Receives: Drug: Frespaciguat
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. Receives: Drug: Frespaciguat
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. Receives: Drug: Frespaciguat
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. Receives: Drug: Frespaciguat
Placebo (Part 1)	Placebo comparator	Participants will receive a single inhaled dose of matching placebo in Part 1. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Who Experienced at Least 1 Adverse Event (AE): All Parts
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.
Measured: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total)
Number of Participants Who Discontinued From the Study Due to an AE: All Parts
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.
Measured: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total)
Percentage Change From Baseline in Minimum Pulmonary Vascular Resistance (PVR): Part 2 Right Heart Catheterization (RHC) 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.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and up to 4.5 hours post-dose

Secondary outcomes (16)

Change From Baseline in Heart Rate (HR) at 0.5 Hours Post-dose: Part 2 RHC Period
HR was assessed at pre-dose in the RHC Period (baseline) and at 0.5 hours post-dose. Baseline HR and change from baseline in HR was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in HR. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 0.5 hours post-dose
Change From Baseline in Heart Rate (HR) at 4.5 Hours Post-dose: Part 2 RHC Period
HR was assessed at pre-dose in the RHC Period (baseline) and at 4.5 hours post-dose. Baseline HR and change from baseline in HR was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in HR. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 4.5 hours post-dose
Change From Baseline in Heart Rate (HR) at 24 Hours Post-dose: Part 2 RHC Period
HR was assessed at pre-dose in the RHC Period (baseline) and at 24 hours post-dose. Baseline HR and change from baseline in HR was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in HR. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 24 hours post-dose
Change From Baseline in Systolic Blood Pressure (SBP) at 0.5 Hours Post-dose: Part 2 RHC Period
SBP was assessed at pre-dose in the RHC Period (baseline) and at 0.5 hours post-dose. Baseline SBP and change from baseline in SBP was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in SBP. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 0.5 hours post-dose
Change From Baseline in Systolic Blood Pressure (SBP) at 4.5 Hours Post-dose: Part 2 RHC Period
SBP was assessed at pre-dose in the RHC Period (baseline) and at 4.5 hours post-dose. Baseline SBP and change from baseline in SBP was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in SBP. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 4.5 hours post-dose
Change From Baseline in Systolic Blood Pressure (SBP) at 24 Hours Post-dose: Part 2 RHC Period
SBP was assessed at pre-dose in the RHC Period (baseline) and at 24 hours post-dose. Baseline SBP and change from baseline in SBP was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in SBP. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 24 hours post-dose
Change From Baseline in Diastolic Blood Pressure (DBP) at 0.5 Hours Post-dose: Part 2 RHC Period
DBP was assessed at pre-dose in the RHC Period (baseline) and at 0.5 hours post-dose. Baseline DBP and change from baseline in DBP was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in DBP. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 0.5 hours post-dose
Change From Baseline in Diastolic Blood Pressure (DBP) at 4.5 Hours Post-dose: Part 2 RHC Period
DBP was assessed at pre-dose in the RHC Period (baseline) and at 4.5 hours post-dose. Baseline DBP and change from baseline in DBP was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in DBP. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 4.5 hours post-dose
Change From Baseline in Diastolic Blood Pressure (DBP) at 24 Hours Post-dose: Part 2 RHC Period
DBP was assessed at pre-dose in the RHC Period (baseline) and at 24 hours post-dose. Baseline DBP and change from baseline in DBP was reported for each panel/dose group that underwent RHC in Part 2, according to treatment planned. Negative values indicate decreases from baseline in DBP. Per protocol, this outcome measure was only assessed during the Part 2 RHC Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 24 hours post-dose
Area Under the Concentration-Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-5475: All Parts
Blood samples were taken at predose and at specified time points postdose to determine the AUC0-inf of MK-5475. AUC0-inf was defined as the area under the concentration-time curve of MK-5475 from time zero to infinity. MK-5475 AUC0-inf was reported by panel/dose group. Per protocol, percent geometric coefficient of variation (%GCV) values were not reported for groups with n<2 participants.
Measured: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Area Under the Concentration-Time Curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-5475: All Parts
Blood samples were taken at predose and at specified time points postdose to determine the AUC0-24hr of MK-5475. AUC0-24hr was defined as the area under the concentration-time curve of MK-5475 from time zero to 24 hours. MK-5475 AUC0-24hr was reported by panel/dose group. For RHC panel/dose groups where sampling was only done up to 4.5 hours, the AUC0-24hr geometric mean represents an extrapolated AUC0-24hr value. Per protocol, %GCV values were not reported for groups with n<2 participants.
Measured: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Maximum Concentration (Cmax) of MK-5475: All Parts
Blood samples were taken at predose and at specified time points postdose to determine the Cmax of MK-5475. Cmax was defined as the maximum concentration of MK-5475 reached. MK-5475 Cmax was reported by panel/dose group. Per protocol, %GCV values were not reported for groups with n<2 participants.
Measured: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Concentration of MK-5475 at 24 Hours Postdose (C24): All Parts
Blood samples were taken at predose and at specified time points postdose to determine the C24 of MK-5475. C24 was defined as the concentration of MK-5475 reached at 24 hours. MK-5475 Cmax was reported by panel/dose group. Per protocol, %GCV values were not reported for groups with n<2 participants.
Measured: 24 hours postdose
Time to Maximum Concentration (Tmax) of MK-5475: All Parts
Blood samples were taken at predose and at specified time points postdose to determine the Tmax of MK-5475. Tmax was defined as the time to maximum concentration of MK-5475. MK-5475 Tmax was reported by panel/dose group.
Measured: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Apparent Terminal Half-life (t1/2) of MK-5475: All Parts
Blood samples were taken at predose and at specified time points postdose to determine the t½ of MK-5475. t½ was defined as the time required to divide the MK-5475 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-5475. MK-5475 t½ was reported by panel/dose group.
Measured: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Percentage Change From Baseline in Pulmonary Blood Volume (PBV) Over Time: Part 2 Functional Respiratory Imaging (FRI) Period
Participants underwent a series of computed tomography (CT) scans with an intravenous (IV) iodinated contrast agent to facilitate assessment of PBV at baseline and at several times points after MK-5475 dosing. Percentage change from baseline (CFB) in PBV was calculated and reported for each dose group that underwent FRI in Part 2. As pre-specified, central tendency for PBV percentage CFB was provided as numerical values rounded to whole numbers. Per protocol, this outcome measure was only assessed during the Part 2 FRI Period for each panel and was not assessed during Part 1.
Measured: Baseline: Pre-dose on Day 1 of FRI Period (up to 227 days) and 1, 3, 8, and 24 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jan 201911 Dec 2020

First posted16 Nov 2018
Study start18 Jan 2019
Primary completion11 Dec 2020
Study completion11 Dec 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: Part 1 of the study will evaluate safety, tolerability, and pharmacokinetics in this population using a sequential study design. Review of available safety data up to 24 hours post dose of at least the first 4 participants must occur prior to escalating to the next dose level. A break to review PK data from Periods 1 and 2 will occur after completion of Period 2. Review of safety will occur after completion of Period 3 in all participants from Panel A, prior to initiation of Part 2. An optional break to review rolling PK data from Panel A Period 3 will be dependent upon exposures observed in Periods 1 and 2.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03744637
Sponsor's protocol ID: 5475-002
Other IDs: MK-5475-002
Status last verified: May 2025
First submitted: 13 Nov 2018
Last updated: 4 Jun 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Bajwa EK, Cislak D, Palcza J, Feng HP, Messina EJ, Reynders T, Denef JF, Corcea V, Lai E, Stoch SA. Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH). Respir Med. 2023 Jan;206:107065. doi: 10.1016/j.rmed.2022.107065. Epub 2022 Nov 29.
PubMed 36521262

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Assess the Effect of Single Doses of MK-5475 on Pulmonary Vascular Resistance in Patients With Moderate to Severe Pulmonary Arterial Hypertension
ClinicalTrials.gov ID: NCT03744637
Acronym / sponsor ID: 5475-002
Conditions: Pulmonary Arterial Hypertension
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 18 Jan 2019 (actual)
Primary completion: 11 Dec 2020 (actual)
Study completion: 11 Dec 2020 (actual)
First posted: 16 Nov 2018 (actual)
Results: Posted 23 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 5
Model description: Part 1 of the study will evaluate safety, tolerability, and pharmacokinetics in this population using a sequential study design. Review of available safety data up to 24 hours post dose of at least the first 4 participants must occur prior to escalating to the next dose level. A break to review PK data from Periods 1 and 2 will occur after completion of Period 2. Review of safety will occur after completion of Period 3 in all participants from Panel A, prior to initiation of Part 2. An optional break to review rolling PK data from Panel A Period 3 will be dependent upon exposures observed in Periods 1 and 2.

Arm	Type	Receives
Panel A: Frespaciguat 120 ug/165 ug/240 ug/240 ug/240 ug (Parts 1 and 2)	Experimental	Drug: FrespaciguatParticipants 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	Drug: FrespaciguatParticipants 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	Drug: FrespaciguatParticipants 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	Drug: FrespaciguatParticipants 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	Drug: PlaceboParticipants will receive a single inhaled dose of matching placebo in Part 1.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Be or have suspected Group 1 pulmonary hypertension as defined by the Nice 2013 Clinical Classification, including: idiopathic PAH, heritable PAH, drug- or toxin-induced PAH, or PAH associated with connective tissue disease or congenital heart disease
Have a Body Mass Index (BMI) ≤35 kg/m2,
Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is a woman of nonchildbearing potential (WONCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) after the last dose of study intervention: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception unless confirmed to be azoospermic (Vasectomized) or secondary to medical cause.
Have a clinical indication for right heart catheterization (RHC) as part of initial work-up or ongoing medical management

Key exclusion criteria (25 listed)

Has pulmonary hypertension subtypes including the following according to Nice 2013 Clinical Classification: human immunodeficiency (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, pulmonary veno-occlusive disease (PVOD) and or pulmonary capillary hemangiomatosis (PCH), persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension owing to left heart diseases, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, valvular disease, congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies, pulmonary hypertension owing to lung diseases and/or hypoxia, Chronic obstructive pulmonary disease, Interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental abnormalities, pulmonary hypertension defined as chronic thromboembolic pulmonary hypertension [CTEPH]), pulmonary hypertension with unclear multifactorial mechanisms, hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy, systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis, metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders, others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental pulmonary hypertension
Has a history of clinically significant endocrine (not including stable diabetes mellitus), gastrointestinal, cardiovascular, hematological, hepatic (not including chronic stable Hepatitis B and Hepatitis C), immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
Is mentally or legally incapacitated, has significant emotional problems
History of cancer (malignancy) except nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated 10 years prior to screening
History of significant multiple and/or severe allergies

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FrespaciguatAlso: MK-5475Single inhaled dose of frespaciguat 120, 165, 240, 300, 360, or 480 ug depending upon randomization	Drug	Panel A: Frespaciguat 120 ug/165 ug/240 ug/240 ug/240 ug (Parts 1 and 2), Panel B: 300 ug/360 ug/360 ug (Part 2), Panel C: 300 ug/360 ug/360 ug (Part 2, Expansion), Panel D: 480 ug/120 ug/120 ug (Part 2)
PlaceboSingle inhaled dose of placebo to match frespaciguat	Drug	Placebo (Part 1)

Primary outcome

Number of Participants Who Experienced at Least 1 Adverse Event (AE): All Parts
Time frame: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total)
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.
Number of Participants Who Discontinued From the Study Due to an AE: All Parts
Time frame: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total)
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.
Percentage Change From Baseline in Minimum Pulmonary Vascular Resistance (PVR): Part 2 Right Heart Catheterization (RHC) Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and up to 4.5 hours post-dose
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.

16 secondary outcomes

Change From Baseline in Heart Rate (HR) at 0.5 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 0.5 hours post-dose
Change From Baseline in Heart Rate (HR) at 4.5 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 4.5 hours post-dose
Change From Baseline in Heart Rate (HR) at 24 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 24 hours post-dose
Change From Baseline in Systolic Blood Pressure (SBP) at 0.5 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 0.5 hours post-dose
Change From Baseline in Systolic Blood Pressure (SBP) at 4.5 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 4.5 hours post-dose
Change From Baseline in Systolic Blood Pressure (SBP) at 24 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 24 hours post-dose
Change From Baseline in Diastolic Blood Pressure (DBP) at 0.5 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 0.5 hours post-dose
Change From Baseline in Diastolic Blood Pressure (DBP) at 4.5 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 4.5 hours post-dose
Change From Baseline in Diastolic Blood Pressure (DBP) at 24 Hours Post-dose: Part 2 RHC Period
Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and 24 hours post-dose
Area Under the Concentration-Time Curve From Hour 0 to Infinity (AUC0-inf) of MK-5475: All Parts
Time frame: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Area Under the Concentration-Time Curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-5475: All Parts
Time frame: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Maximum Concentration (Cmax) of MK-5475: All Parts
Time frame: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Concentration of MK-5475 at 24 Hours Postdose (C24): All Parts
Time frame: 24 hours postdose
Time to Maximum Concentration (Tmax) of MK-5475: All Parts
Time frame: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Apparent Terminal Half-life (t1/2) of MK-5475: All Parts
Time frame: Part 1 and Part 2 Period 1: Predose and 0.1, 0.25, 0.5, 1, 2, 3, 4, 8, and 24 hours post-dose; RHC Period: predose and 0.25, 0.5, 1, 2, 3, 4, and 4.5 hours; FRI Period: predose and 1, 3, 8, and 24 hours postdose (Panel D also 0.25, 0.5, 2, 4 hours)
Percentage Change From Baseline in Pulmonary Blood Volume (PBV) Over Time: Part 2 Functional Respiratory Imaging (FRI) Period
Time frame: Baseline: Pre-dose on Day 1 of FRI Period (up to 227 days) and 1, 3, 8, and 24 hours post-dose

Results and safety

Results posted to the registry on 23 Feb 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-5475 120 ug/MK-5475 165 ug/MK-5475 240 ug/MK-5475 240 ug/MK-5475 240 ug (Panel A)	2	2
MK-5475 120 ug/Placebo/MK-5475 240 ug/MK-5475 240 ug/MK-5475 240 ug (Panel A)	2	2
MK-5475 120 ug/MK-5475 165 ug/Placebo/MK-5475 240 ug/MK-5475 240 ug (Panel A)	2	2
Placebo/MK-5475 165 ug/MK-5475 240 ug/MK-5475 240 ug/MK-5475 240 ug (Panel A)	1	1
Placebo/MK-5475 165 ug/MK-5475 240 ug (Panel A)	1	1
MK-5475 300 ug/ MK-5475 165 ug/ MK-5475 165 ug (Panel B)	1	1
MK-5475 300 ug/ MK-5475 360 ug/ MK-5475 360 ug (Panels B+C)	8	8
MK-5475 300 ug/ MK-5475 120 ug/ MK-5475 120 ug (Panel C)	4	4
MK-5475 480 ug/ MK-5475 120 ug/ MK-5475 120 ug (Panel D)	3	3
MK-5475 480 ug/ MK-5475 120 ug (Panel D)	1	1

Primary outcome: Number of Participants Who Experienced at Least 1 Adverse Event (AE): All Parts

Time frame: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total). Count of participants. Unit: Participants

Measure	MK-5475 120 ug: Part 1 (Panel A) n = 6	MK-5475 165 ug: Part 1 (Panel A) n = 6	MK-5475 240 ug: Part 1 (Panel A) n = 6	MK-5475 300 ug: Part 2 Period 1 (Panels B+C) n = 13	MK-5475 480 ug: Part 2 Period 1 (Panel D) n = 4	Placebo: Part 1 n = 6	MK-5475 120 ug: RHC (Panel D) n = 7	MK-5475 165 ug: RHC (Panel B) n = 1	MK-5475 240 ug: RHC (Panel A) n = 7	MK-5475 360 ug: RHC (Panels B+C) n = 8	MK-5475 120 ug: FRI (Panels C+D) n = 8	MK-5475 165 ug: FRI (Panel B) n = 1	MK-5475 240 ug: FRI (Panel A) n = 7	MK-5475 360 ug: FRI (Panels B+C) n = 8
Value	2	1	3	5	2	4	5	1	6	4	1	0	0	4

Population analysed: All participants who received ≥1 dose of investigational treatment were analyzed according to treatment received.

Primary outcome: Number of Participants Who Discontinued From the Study Due to an AE: All Parts

Time frame: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total). Count of participants. Unit: Participants

Measure	MK-5475 120 ug: Part 1 (Panel A) n = 6	MK-5475 165 ug: Part 1 (Panel A) n = 6	MK-5475 240 ug: Part 1 (Panel A) n = 6	MK-5475 300 ug: Part 2 Period 1 (Panels B+C) n = 13	MK-5475 480 ug: Part 2 Period 1 (Panel D) n = 4	Placebo: Part 1 n = 6	MK-5475 120 ug: RHC (Panel D) n = 7	MK-5475 165 ug: RHC (Panel B) n = 1	MK-5475 240 ug: RHC (Panel A) n = 7	MK-5475 360 ug: RHC (Panels B+C) n = 8	MK-5475 120 ug: FRI (Panels C+D) n = 8	MK-5475 165 ug: FRI (Panel B) n = 1	MK-5475 240 ug: FRI (Panel A) n = 7	MK-5475 360 ug: FRI (Panels B+C) n = 8
Value	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Population analysed: All participants who received ≥1 dose of investigational treatment were analyzed according to treatment received.

Primary outcome: Percentage Change From Baseline in Minimum Pulmonary Vascular Resistance (PVR): Part 2 Right Heart Catheterization (RHC) Period

Time frame: Baseline: Pre-dose on Day 1 of RHC Period (up to 185 days) and up to 4.5 hours post-dose. Mean (Standard Deviation). Unit: Percentage change

Measure	MK-5475 120 ug: Part 1 (Panel A) n = 0	MK-5475 165 ug: Part 1 (Panel A) n = 0	MK-5475 240 ug: Part 1 (Panel A) n = 0	MK-5475 300 ug: Part 2 Period 1 (Panels B+C) n = 0	MK-5475 480 ug: Part 2 Period 1 (Panel D) n = 0	Placebo: Part 1 n = 0	MK-5475 120 ug: RHC (Panel D) n = 7	MK-5475 165 ug: RHC (Panel B) n = 1	MK-5475 240 ug: RHC (Panel A) n = 7	MK-5475 360 ug: RHC (Panels B+C) n = 8	MK-5475 120 ug: FRI (Panels C+D) n = 0	MK-5475 165 ug: FRI (Panel B) n = 0	MK-5475 240 ug: FRI (Panel A) n = 0	MK-5475 360 ug: FRI (Panels B+C) n = 0
Value	–	–	–	–	–	–	-20.77 (13.88)	13.01 (NA)	-29.46 (13.72)	-29.25 (17.58)	–	–	–	–

Population analysed: All participants who received ≥1 dose of MK-5475, who complied with the protocol without major protocol deviations, and who underwent the RHC procedure and had available data were analyzed according to treatment received.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-5475 120 ug: Part 1 (Panel A)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
MK-5475 165 ug: Part 1 (Panel A)	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
MK-5475 240 ug: Part 1 (Panel A)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
MK-5475 300 ug: Part 2 Period 1 (Panels B+C)	0 of 13 (0%)	5 of 13 (38.5%)	0 of 13
MK-5475 480 ug: Part 2 Period 1 (Panel D)	0 of 4 (0%)	2 of 4 (50%)	0 of 4
Placebo: Part 1	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
MK-5475 120 ug: RHC (Panel D)	0 of 7 (0%)	5 of 7 (71.4%)	0 of 7
MK-5475 165 ug: RHC (Panel B)	0 of 1 (0%)	1 of 1 (100%)	0 of 1
MK-5475 240 ug: RHC (Panel A)	0 of 7 (0%)	6 of 7 (85.7%)	0 of 7
MK-5475 360 ug: RHC (Panels B+C)	0 of 8 (0%)	4 of 8 (50%)	0 of 8
MK-5475 120 ug: FRI (Panels C+D)	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
MK-5475 165 ug: FRI (Panel B)	0 of 1 (0%)	0 of 1 (0%)	0 of 1
MK-5475 240 ug: FRI (Panel A)	0 of 7 (0%)	0 of 7 (0%)	0 of 7
MK-5475 360 ug: FRI (Panels B+C)	0 of 8 (0%)	4 of 8 (50%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 36521262Bajwa EK, Cislak D, Palcza J, Feng HP, Messina EJ, Reynders T, Denef JF, Corcea V, Lai E, Stoch SA. Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH). Respir Med. 2023 Jan;206:107065. doi: 10.1016/j.rmed.2022.107065. Epub 2022 Nov 29.
Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Frespaciguat in people with Pulmonary Arterial Hypertension, run by Merck Sharp & Dohme LLC at 1 site in Moldova.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced at Least 1 Adverse Event (AE): All Parts (time frame: Up to ~14 days after last dose of treatment period (Up to ~32 weeks total)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03744637, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.