Phase 1
N=9
Frespaciguat (MK-5475) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (MK-5475-006)
Pulmonary Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT04370873 ↗Enrolled (actual)
9
Serious AEs
8.7%
Results posted
Apr 2024
Primary outcome: Primary: Percentage of Participants Who Experienced at Least 1 Adverse Event (AE) — 33.3; 33.3; 33.3; 80.0 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Frespaciguat (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Experienced at Least 1 Adverse Event (AE) |
33.3; 33.3; 33.3; 80.0 | — |
| PRIMARY Percentage of Participants Who Discontinued Study Drug Due to an AE |
0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Percentage Change From Baseline to Day 28 in Pulmonary Vascular Resistance (PVR): Part 2 |
-21.23; -5.39 | — |
| SECONDARY Plasma Area Under the Concentration Time-Curve From 0 to Infinity (AUC0-inf) of MK-5475: Part 1 |
3.32; 4.03 | — |
| SECONDARY Plasma Area Under the Concentration Time-Curve From 0 to 24 Hours (AUC0-24) of MK-5475: Part 1 |
3.31; 4.22 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of MK-5475: Part 1 |
0.830; 0.970 | — |
| SECONDARY Plasma Concentration 24 Hours Postdose (C24) of MK-5475: Part 1 |
0.02 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of MK-5475: Part 1 |
1.00; 1.00 | — |
| SECONDARY Plasma Apparent Terminal Half-Life (t½) of MK-5475: Part 1 |
2.13; 2.81 | — |
| SECONDARY Cmax Accumulation Ratio of MK-5475: Part 1 |
1.17 | — |
| SECONDARY AUC0-24 Accumulation Ratio of MK-5475: Part 1 |
1.27 | — |
| SECONDARY AUC0-inf Accumulation Ratio of MK-5475: Part 1 |
1.21 | — |
| SECONDARY AUC0-inf of MK-5475: Part 2 |
NA; 1.98 | — |
| SECONDARY AUC0-24 of MK-5475: Part 2 |
NA; 1.97 | — |
| SECONDARY Cmax of MK-5475: Part 2 |
0.348; 0.397 | — |
| SECONDARY Plasma Concentration 24 Hours Postdose (C24) of MK-5475: Part 2 |
— | — |
| SECONDARY Tmax of MK-5475: Part 2 |
1.50; 1.50 | — |
| SECONDARY t½ of MK-5475: Part 2 |
NA; 2.06 | — |
| SECONDARY AUC0-3 Accumulation Ratio of MK-5475: Part 2 |
1.11 | — |
| SECONDARY Cmax Accumulation Ratio of MK-5475: Part 2 |
1.14 | — |
| SECONDARY Percent Change From Baseline in Pulmonary Blood Volume (PBV) at Day 28: Part 2 |
-0.3; -2.8 | — |
Summary
The primary objectives of this study are to assess the safety/tolerability and efficacy (by evaluating changes in pulmonary vascular resistance [PVR] and pulmonary blood volume [PBV]) of frespaciguat in participants with pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD). The primary hypothesis is that 28 days of frespaciguat treatment is superior to placebo treatment in reduction of PVR.
Eligibility Criteria
Inclusion Criteria
- Is male or female, from 40 to 80 years of age inclusive at the time of signing informed consent.
- Be judged to have no untreated, clinically significant health issue from other comorbidities based on medical history, physical examination, vital signs and electrocardiograms performed at the screening visit(s)
- Be judged to have no untreated, clinically significant health issue from other comorbidities based on laboratory safety tests performed at the screening visit(s)
- 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) (eg, 5 terminal half-lives) plus an additional 90 days (a spermatogenesis cycle) 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 agrees to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause
- A 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 3 m/s or significant right heart enlargement and or reduced right heart function
Exclusion Criteria
- Has pulmonary hypertension subtypes including the following according to Nice 2013 Clinical classification. This includes Group 1 Pulmonary arterial hypertension (PAH): Idiopathic PAH, Heritable PAH including Bone morphogenetic protein receptor type II (BMPR2), Activin A receptor type II-like kinase-1 (ALK1), endoglin, Sterile alpha motif domain-containing protein 9 (SMAD9), caveolin 1 (CAV1), potassium two-pore-domain channel subfamily K member 3 (KCNK3) and unknown, Drug and toxin-induced PAH, PAH associated with Connective tissue disease, HIV infection, Portal hypertension, Congenital heart disease (unrepaired and not requiring repair or repaired simple cardiac defects at least 1year status post corrective surgery, with no clinically significant residual shunt), Schistosomiasis, Chronic hemolytic anemia, Persistent pulmonary hypertension of the newborn (PPHN), and Pulmonary veno-occlusive disease (PVOD) and or pulmonary capillary hemangiomatosis (PCH); Group 2 Pulmonary hypertension owing to left heart diseases including Left ventricular Systolic dysfunction, Left ventricular Diastolic dysfunction, Valvular disease, Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies; Group 3 Pulmonary hypertension owing to lung diseases or hypoxia not associated with COPD including Interstitial lung disease, Other pulmonary diseases with mixed restrictive and obstructive pattern, Sleep-disordered breathing (mild obstructive sleep apnea (OSA) may be permitted with sponsor consultation), Alveolar hypoventilation disorders. Chronic exposure to high altitude, Developmental abnormalities; Group 4 Pulmonary hypertension defined as Chronic thromboembolic pulmonary hypertension [CTEPH]); and Group 5 Pulmonary Hypertension with unclear multifactorial mechanisms including Hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, Splenectomy, Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleimyomatosis, neurofibromatosis, vasculitis, Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders, and Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental pulmonary hypertension.
- Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic (not including chronic stable Hep B and C), immunological, renal, respiratory (not including PH-COPD), genitourinary, or major neurological (including stro
Data sourced from ClinicalTrials.gov (NCT04370873). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.