A Phase II Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Single Inhaled Doses of Ensifentrine-glycopyrrolate Fixed Dose Combination, Ensifentrine, and Glycopyrrolate in Subjects With Chronic Obstructive Pulmonary Disease

NCT07132983 | Completed Phase 2 FDA Drug

• 1 other identifier: RPL554-CO-210
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

This study will assess the pharmacokinetics (PK), pharmacodynamics (PD) and safety of ensifentrine and glycopyrrolate fixed dose (FDC) product, the individual components of the FDC (ensifentrine and glycopyrrolate, each in the FDC formulation), ensifentrine 1.5 mg in the FDC formulation and ensifentrine 3 mg in the marketed formulation each administered via a standard jet nebulizer, in adult participants with chronic obstructive pulmonary disease (COPD).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease; COPD; bronchodilator; ensifentrine-glycopyrrolate

Outcome Measures

Primary Outcomes (14)

• 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)

Study Arms (5)

Treatment A: Ensifentrine plus Glycopyrrolate

EXPERIMENTAL

(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

Drug: Ensifentrine 3 mg; Drug: Glycopyrrolate 42.5 mcg

Treatment B: Ensifentrine monotherapy

EXPERIMENTAL

(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

Drug: Ensifentrine 3 mg

Treatment C: Glycopyrrolate monotherapy

EXPERIMENTAL

(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

Drug: Glycopyrrolate 42.5 mcg

Treatment D: Ensifentrine monotherapy

EXPERIMENTAL

(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

Drug: Ensifentrine 1.5 mg

Treatment E: Ensifentrine monotherapy (marketed formulation)

EXPERIMENTAL

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

Drug: Ensifentrine 3 mg (marketed formulation)

Interventions

Ensifentrine 3 mg DRUG

Single dose, administered by oral inhalation using a standard jet nebulizer

Treatment A: Ensifentrine plus Glycopyrrolate; Treatment B: Ensifentrine monotherapy

Glycopyrrolate 42.5 mcg DRUG

Single dose, administered by oral inhalation using a standard jet nebulizer

Treatment A: Ensifentrine plus Glycopyrrolate; Treatment C: Glycopyrrolate monotherapy

Ensifentrine 1.5 mg DRUG

Single dose, administered by oral inhalation using a standard jet nebulizer

Treatment D: Ensifentrine monotherapy

Ensifentrine 3 mg (marketed formulation) DRUG

Single dose, administered by oral inhalation using a standard jet nebulizer

Treatment E: Ensifentrine monotherapy (marketed formulation)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males are eligible to participate if they to use contraception or abstinence, and refrain from donating fresh unwashed semen during the study and for at least 30 days post-study
• Females are eligible to participate if they are not pregnant, breastfeeding and if one of the following conditions apply:
• Not a woman of child-bearing potential OR
• Agrees to follow the contraceptive guidance and not to donate eggs for the purpose of reproduction from screening throughout the study and for at least 30 days post-study
• Current or former cigarette smokers with a history of cigarette smoking ≥ 10 pack years as of signing the ICF \[number of pack years = (number of cigarettes per day / 20) × number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to signing the ICF. Smoking cessation programs are permitted during the study
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD
• Post-bronchodilator (4 puffs of albuterol) spirometry during the Screening Period demonstrating both the following:
• FEV1/forced vital capacity (FVC) ratio of \< 0.70 AND
• FEV1 ≥ 40 % and ≤ 80% of predicted normal
• A posterior-anterior chest x-ray (CXR) during the Screening Period or within 12 months prior to signing the ICF showing no clinically significant abnormalities unrelated to COPD. If a CXR within the past 12 months is not available but a computed tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR
• Capable of withholding from short-acting bronchodilators for at least 4 hours if using albuterol and for at least 6 hours if using ipratropium prior to pre-dose of blinded study medication spirometry testing
• Anatomical features of peripheral veins that allow the ability to draw sufficient blood volume for all study samples
• Capable of using the study supplied jet nebulizer correctly
• Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines
• Willing and able to attend all study visits and adhere to all study assessments and procedures

You may not qualify if:

• Concomitant clinically significant pulmonary disease other than COPD (e.g., asthma, tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea (unless controlled with stable continuous positive airway pressure use), known alpha-1 antitrypsin deficiency, core pulmonale or other non-specific pulmonary disease)
• Within 6 months prior to randomization, a COPD exacerbation requiring hospitalization
• Within 3 months prior to randomization, use of therapies for a COPD exacerbation (e.g., oral, intravenous, or intramuscular glucocorticoids; antibiotics; theophylline; roflumilast)
• History of life-threatening COPD, including Intensive Care Unit admission and/or requiring intubation
• Severe comorbidities including:
• Unstable cardiac disease (myocardial infarction within 1 year prior to randomization, unstable angina within 6 months prior to randomization, unstable or life-threatening arrhythmia requiring intervention within 3 months prior to randomization, diagnosis of New York Heart Association (NYHA) class III or IV heart disease)
• Any other clinically significant medical conditions including uncontrolled diseases (e.g., endocrine, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric \[e.g., untreated significant depression, anxiety, or history of suicidality\], or ophthalmic diseases) that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject
• History of or clinically significant on-going bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within 6 months prior to randomization
• History of narrow angle glaucoma
• History of hypersensitivity or intolerance to aerosol medications, albuterol, ensifentrine, glycopyrrolate, any excipients/components of the study medications, anticholinergic agents, or sympathomimetic amines
• History of or current malignancy of any organ system, treated or untreated within the 5 years prior to signing the ICF, except for localized basal or squamous cell carcinoma of the skin
• Other significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator
• Findings on physical examination that the Investigator considers to be clinically significant during the Screening Period
• Prior or current use of Ohtuvayre (ensifentrine)
• Previous lung resection or lung reduction surgery within 1-year of randomization

Sponsors & Collaborators

• Verona Pharma plc: lead

Study Sites (4)

Clinical Research of West Florida Inc - Clearwater

Clearwater, Florida, 33765-2616, United States

Location

Clinical Research of West Florida Inc - Tampa

Tampa, Florida, 33606-1246, United States

Location

Midwest Chest Consultants PC

Saint Charles, Missouri, 63301, United States

Location

Velocity Clinical Research - Spartanburg - PPDS

Spartanburg, South Carolina, 29303-4225, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine; Glycopyrrolate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 20, 2025
• Study Start: October 6, 2025
• Primary Completion: November 28, 2025
• Study Completion: November 28, 2025
• Last Updated: January 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)