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Ensifentrine

Phase 3

Chronic Obstructive Pulmonary Disease | Small molecule | Respiratory |Merck & Company, Inc.|Last Updated: Aug 28, 2026

Target and mechanism

Molecular targetPDE3A, PDE3B, PDE4A, PDE4D, PDE4B, PDE4C
Target classInhibitor
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials4
Total Enrollment2,083

FDA Designations

No designations recorded

Clinical trial landscape

Ensifentrine · 5 trials · 2 indications

Phase 3 2Phase 2 3
NCT04535986A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPDChronic Obstructive Pulmonary Disease
COMPLETED763 Analytics
NCT04542057A Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPDChronic Obstructive Pulmonary Disease
COMPLETED790 Analytics
PHASE3COMPLETED
A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
Chronic Obstructive Pulmonary DiseaseUnlock trial analytics
PHASE3COMPLETED
A Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
Chronic Obstructive Pulmonary DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Least Square (LS) Mean Change From Baseline in Average Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) at Week 12
Baseline (pre-dose on Day 1) and Week 12

Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-12h was defined as AUC over 12 hours of the FEV1, divided by 12 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.

Ensifentrine single dose area under the curve from time 0 to time t (AUC0-t)
Day 1 through 48 hours after each dose of study medication
Ensifentrine single dose area under the curve from time 0 extrapolated to infinity (AUC0-inf)
Day 1 through 48 hours after each dose of study medication
Ensifentrine single dose maximum observed concentration (Cmax)
Day 1 through 48 hours after each dose of study medication
Glycopyrronium single dose AUC0-t
Day 1 through 48 hours after each dose of study medication
Glycopyrronium single dose AUC0-inf
Day 1 through 48 hours after each dose of study medication
Glycopyrronium single dose Cmax
Day 1 through 48 hours after each dose of study medication
Change from average baseline in forced expiratory volume over 1 second (FEV1) to FEV1 area under the curve versus time from time 0 to 12 hours (AUC0-12h)
Baseline through 12 hours after each dose of study medication
Change from average baseline FEV1 to average FEV1 area under the curve versus time from time 0 to 4 hours (AUC0-4h)
Baseline through 4 hours after each dose of study medication
Change from average baseline FEV1 to peak FEV1 measured over 4 hours post-dose
Baseline through 4 hours after each dose of study medication
Change from average baseline FEV1 to 12-hour post-dose (evening trough) FEV1
Baseline through 12 hours after each dose of study medication
Incidence of treatment emergent adverse events (TEAEs)
From first dose through the end of study (approximately 6 weeks)
Change from baseline in QTcF as measured by 12-lead ECG
Baseline and visits 2, 5, 8, 11, and 14
Change from baseline in blood pressure
Baseline through end of study (approximately 6 weeks)
Change from baseline in heart rate
Baseline through end of study (approximately 6 weeks)
Change from baseline in average forced expiry volume in 1 second (FEV1) area under the curve versus time, from time 0 to 4 hours (AUC0-4h)
Baseline and Day 28
The change from baseline in sputum neutrophils at Week 8 (absolute change in cell numbers)
Week 8

To measure the effect of nebulized ensifentrine on sputum absolute neutrophil count after twice daily dosing.

Secondary Endpoints

LS Mean Change From Baseline FEV1 to Peak FEV1 at Day 1 and Weeks 6, 12 and 24
Baseline (pre-dose on Day 1), post-dose on Day 1, Weeks 6, 12, and 24
LS Mean Change From Baseline to the Mean Weekly Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24
Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24
LS Mean Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 6, 12 and 24
Baseline (pre-dose on Day 1) and Weeks 6, 12, and 24
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm 1EXPERIMENTALEnsifentrine Nebulized Suspension; 3 mg BID
Arm 2PLACEBO_COMPARATORPlacebo Nebulized BID
Treatment A: Ensifentrine plus GlycopyrrolateEXPERIMENTAL(fixed-dose combination formulation) Subjects will receive a single dose of study medication in each treatment period followed by a 7 to 9-day washout period before receiving the next treatment in the sequence they were assigned to
Treatment B: Ensifentrine monotherapyEXPERIMENTAL(fixed-dose combination formulation) Subjects will receive a single dose of study medication in each treatment period followed by a 7 to 9-day washout period before receiving the next treatment in the sequence they were assigned to
Treatment C: Glycopyrrolate monotherapyEXPERIMENTAL(fixed-dose combination formulation) Subjects will receive a single dose of study medication in each treatment period followed by a 7 to 9-day washout period before receiving the next treatment in the sequence they were assigned to
Treatment D: Ensifentrine monotherapyEXPERIMENTAL(fixed-dose combination formulation) Subjects will receive a single dose of study medication in each treatment period followed by a 7 to 9-day washout period before receiving the next treatment in the sequence they were assigned to
Treatment E: Ensifentrine monotherapy (marketed formulation)EXPERIMENTALSubjects will receive a single dose of study medication in each treatment period followed by a 7 to 9-day washout period before receiving the next treatment in the sequence they were assigned to
Treatment Arm A: Ensifentrine plus GlycopyrrolateEXPERIMENTALEnsifentrine 3 mg / Glycopyrrolate 42.5 mcg
Treatment Arm B: Ensifentrine plus GlycopyrrolateEXPERIMENTALEnsifentrine 3 mg / Glycopyrrolate 21.25 mcg
Treatment Arm C: GlycopyrrolateACTIVE_COMPARATORGlycopyrrolate monotherapy 42.5 mcg
Treatment Arm D: GlycopyrrolateACTIVE_COMPARATORGlycopyrrolate monotherapy 21.25 mcg
Treatment Arm E: EnsifentrineACTIVE_COMPARATOREnsifentrine monotherapy 3 mg
Treatment Arm F: PlaceboPLACEBO_COMPARATORPlacebo
Treatment Sequence 1EXPERIMENTALTreatment Period 1 (blinded Ensifentrine) followed by Treatment Period 2 (blinded Placebo)
Treatment Sequence 2EXPERIMENTALTreatment Period 1 (blinded Placebo) followed by Treatment Period 2 (blinded Ensifentrine)

Interventions

NameTypeDescription
EnsifentrineDRUGDosage Formulation: Ensifentrine Nebulizer suspension Dosage 3mg Frequency: Twice Daily for 24 weeks or 48 weeks
PlaceboDRUGDosage Formulation: Ensifentrine Placebo Nebulizer solution Frequency: Twice Daily for 24 weeks or 48 weeks
Ensifentrine 3 mgDRUGSingle dose, administered by oral inhalation using a standard jet nebulizer
Glycopyrrolate 42.5 mcgDRUGSingle dose, administered by oral inhalation using a standard jet nebulizer
Ensifentrine 1.5 mgDRUGSingle dose, administered by oral inhalation using a standard jet nebulizer
Ensifentrine 3 mg (marketed formulation)DRUGSingle dose, administered by oral inhalation using a standard jet nebulizer
Glycopyrrolate 21.25 mcgDRUGAdministered by a standard jet nebulizer, twice daily for 28 consecutive days
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Eligibility Criteria

Age Range40 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites122

Inclusion Criteria: Informed Consent 1. Capable of giving informed consent indicating that they understand the purpose of the study and study procedures and agree to comply with the requirements and restrictions listed in the informed consent form (ICF). Age and Sex 2. Age: Patient must be 40 ...

Countries:United StatesBulgariaCzechiaGermanyGreeceHungaryPolandRomaniaRussiaSlovakiaSouth KoreaUnited KingdomBelgiumCanadaDenmarkEstoniaSpain
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Recent Changes (Last 90 Days)

HIGHAug 28, 2026NCT07016412Status: ACTIVE_NOT_RECRUITING → COMPLETED
HIGHAug 28, 2026NCT07016412Status: ACTIVE_NOT_RECRUITING → COMPLETED
MEDIUMAug 1, 2026NCT07016412Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMAug 1, 2026NCT07016412Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMAug 1, 2026NCT07016412Status: RECRUITING → ACTIVE_NOT_RECRUITING

Frequently asked questions about Ensifentrine

What is Ensifentrine used for?

Ensifentrine is an investigational small molecule being developed for the treatment of chronic obstructive pulmonary disease (COPD). It is currently in Phase 2 clinical development and has been studied in multiple trials involving patients with COPD.

Who is developing Ensifentrine?

Ensifentrine is being developed by Merck & Company, Inc., which trades under the ticker MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with COPD.

What phase is Ensifentrine in?

Ensifentrine is currently in Phase 2 clinical development for COPD. While some completed trials have been Phase 3, the drug's overall development stage is Phase 2, and it remains investigational and not yet approved.

What clinical trials is Ensifentrine in?

Ensifentrine has been studied in several clinical trials, including NCT04535986, a Phase 3 trial in COPD; NCT05270525, a Phase 2 trial examining sputum markers of inflammation; NCT07016412, a Phase 2b dose-ranging study of an ensifentrine-glycopyrrolate combination; and NCT07132983, a Phase 2 pharmacokinetic study.

Is Ensifentrine the same as Ensifentrine-glycopyrrolate?

Ensifentrine and ensifentrine-glycopyrrolate are related but distinct. Ensifentrine is a single agent, while ensifentrine-glycopyrrolate is a fixed-dose combination of ensifentrine with glycopyrrolate. Both have been evaluated in clinical trials for COPD.