Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication OHTUVAYRE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. OHTUVAYRE is a phosphodiesterase 3 (PDE3) inhibitor and phosphodiesterase 4 (PDE4) inhibitor indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. ( 1 ) FDA label
Also known as Nebulized Ensifentrine, MK-5884, RPL554
Ensifentrine · 15 trials · 9 indications
The annualized rate of moderate or severe exacerbations over 52 weeks will be reported.
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.
Spirometry will be performed to determine the FEV1. Change from baseline in average FEV1 area under the curve from 0 to 4 hours on Day 28 will be reported.
To measure the effect of nebulized ensifentrine on sputum absolute neutrophil count after twice daily dosing.
Area under the curve from 0 to 12 hours after single dose drug administration.
Pharmacokinetic Parameter Cmax after a Single Dose
Area under the curve at maximum concentration 0-24 hrs after single dose drug administration
RPL554 Plasma Pharmacokinetics concentration after single dose
Change from Baseline FEV1 to Peak FEV1 (over 4 hours) after morning dosing on Day 7
RPL554 Plasma pharmacokinetics AUC0-12 (Area under the Curve) after single dose
RPL554 Area under the curve at maximum concentration after a single dose
Change from Baseline FEV1 to Peak FEV1 (over 4 hours) on Day 7
Change from baseline FEV1 to peak FEV1 (measured as the greatest value in the 4 hours post-dose after the morning dose) on Day 3
Spirometry assessments were used to assess pulmonary function including the forced expiratory volume in 1 second (FEV1). Peak FEV1 at Week 4 was defined as the maximum post-dose value among the 30 minutes, 1, 2 and 3 hour assessments collected at Visit 6. Baseline was defined as the FEV1 pre-dose assessment (-15 minutes) collected at Visit 2. A mixed model for repeated measures (MMRM) was used to model the change from baseline FEV1 using baseline FEV1 as a continuous fixed effect, randomized treatment, week and treatment-by-week as categorical fixed effect, and patient as random effect. The least squares (LS) mean change from baseline FEV1 to peak FEV1 (as measured over 3 hours) at Week 4 is presented.
Area under the curve (AUC)
Maximum plasma concentration (Cmax) after a single dose of RPL554
Time to maximum concentration (Tmax) after a single dose of RPL554
Half life (t1/2) of RPL554
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing
FEV1
Blood pressure and pulse rate
Biochemistry, haematology and urinalysis
Continuous heart monitoring
| Arm | Type | Description |
|---|---|---|
| Ensifentrine | EXPERIMENTAL | Participants, who meet the criteria of being on standard of care (SOC) background treatment receive ensifentrine twice a day (bid) by oral inhalation via a standard jet nebulizer for up to 52 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants, who meet the criteria of being on SOC background treatment receive placebo bid by oral inhalation via a standard jet nebulizer for up to 52 weeks. |
| Arm 1 | EXPERIMENTAL | Ensifentrine Nebulized Suspension; 3 mg BID |
| Arm 2 | PLACEBO_COMPARATOR | Placebo Nebulized BID |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Treatment Arm A: Ensifentrine plus Glycopyrrolate | EXPERIMENTAL | Participants will receive ensifentrine 3 mg / glycopyrrolate 42.5 mcg twice a day for up to 28 days via oral inhalation by a standard jet nebulizer. |
| Treatment Arm B: Ensifentrine plus Glycopyrrolate | EXPERIMENTAL | Participants will receive ensifentrine 3 mg / glycopyrrolate 21.25 mcg twice a day for up to 28 days via oral inhalation by a standard jet nebulizer. |
| Treatment Arm C: Glycopyrrolate | ACTIVE_COMPARATOR | Participants will receive glycopyrrolate monotherapy 42.5 mcg twice a day for up to 28 days via oral inhalation by a standard jet nebulizer. |
| Treatment Arm D: Glycopyrrolate | ACTIVE_COMPARATOR | Participants will receive glycopyrrolate monotherapy 21.25 mcg twice a day for up to 28 days via oral inhalation by a standard jet nebulizer. |
| Treatment Arm E: Ensifentrine | ACTIVE_COMPARATOR | Participants will receive ensifentrine monotherapy 3 mg twice a day for up to 28 days via oral inhalation by a standard jet nebulizer. |
| Treatment Arm F: Placebo | PLACEBO_COMPARATOR | Participants will receive placebo twice a day for up to 28 days via oral inhalation by a standard jet nebulizer. |
| Treatment Arm 1: Ensifentrine | EXPERIMENTAL | - |
| Treatment Arm 2: Placebo | PLACEBO_COMPARATOR | - |
| Treatment Sequence 1 | EXPERIMENTAL | Treatment Period 1 (blinded Ensifentrine) followed by Treatment Period 2 (blinded Placebo) |
| Treatment Sequence 2 | EXPERIMENTAL | Treatment Period 1 (blinded Placebo) followed by Treatment Period 2 (blinded Ensifentrine) |
| RPL554 100 mcg | EXPERIMENTAL | Part A: Patients receive 1 dose of either RPL554 100mcg via metered dose inhaler. Part B: not applicable |
| RPL554 300 mcg | EXPERIMENTAL | Part A: Patients receive 1 dose of RPL554 300mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 300mcg via metered dose inhaler in crossover fashion. |
| RPL554 1000 mcg | EXPERIMENTAL | Part A: Patients receive 1 dose of RPL554 1000mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 3000mcg via metered dose inhaler in crossover fashion. |
| RPL554 3000 mcg | EXPERIMENTAL | Part A: Patients receive 1 dose of either RPL554 3000mcg via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 3000mcg via metered dose inhaler in crossover fashion. |
| RPL554 6000 mcg | EXPERIMENTAL | Part A: Patients receive 1 dose of either RPL554 6000mcg via metered dose inhaler. Part B: not applicable |
| RPL554 Placebo | PLACEBO_COMPARATOR | Part A: Patients receive 1 dose of RPL554 placebo via metered dose inhaler. Part B: Patients receive repeat doses of RPL554 placebo via metered dose inhaler in crossover fashion. |
| Part A: RPL554 | ACTIVE_COMPARATOR | Placebo controlled, parallel group single dose. Five of the 6 treatment arms will be double-blind and one will be single-blind |
| Part B: RPL554 | ACTIVE_COMPARATOR | Double-blind, placebo-controlled, complete block cross-over |
| 1.5 mg RPL554 and tiotropium/olodaterol | EXPERIMENTAL | 1.5 mg RPL554 suspension administered using a nebulizer twice daily plus 5 mcg/5 mcg tiotropium/olodaterol (Respimat) administered once daily |
| 6 mg RPL554 and tiotropium/olodaterol | EXPERIMENTAL | 6 mg RPL554 suspension administered using a nebulizer twice daily plus 5 mcg/5 mcg tiotropium/olodaterol (Respimat) administered once daily |
| Placebo and tiotropium/olodaterol | EXPERIMENTAL | Placebo administered using a nebulizer twice daily plus 5 mcg/5 mcg tiotropium/olodaterol (Respimat) administered once daily |
| 0.75 mg RPL554 | EXPERIMENTAL | - |
| 1.5 mg RPL554 | EXPERIMENTAL | - |
| 3 mg RPL554 | EXPERIMENTAL | - |
| 6 mg RPL554 | EXPERIMENTAL | - |
| Higher Dose RPL554 | EXPERIMENTAL | Single dose of inhaled 6 mg RPL554 |
| Lower dose RPL554 | EXPERIMENTAL | Single dose of inhaled 1.5 mg RPL554 |
| Lower Dose Nebulised Treatment | EXPERIMENTAL | 1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days |
| Higher Dose Nebulised Treatment | EXPERIMENTAL | 6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days |
| RPL554 Dose 1 | EXPERIMENTAL | 0.4 mg single dose nebulised RPL554 |
| RPL554 Dose 2 | EXPERIMENTAL | 1.5 mg single dose nebulised RPL554 |
| RPL554 Dose 3 | EXPERIMENTAL | 6 mg single dose nebulised RPL554 |
| RPL554 Dose 4 | EXPERIMENTAL | 24 mg single dose nebulised RPL554 |
| Salbutamol Dose 1 | ACTIVE_COMPARATOR | 2.5 mg single dose nebulised salbutamol |
| Salbutamol Dose 2 | ACTIVE_COMPARATOR | 7.5 mg single dose nebulised salbutamol |
| Dummy solution | PLACEBO_COMPARATOR | Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C) |
| RPL554 suspension | EXPERIMENTAL | Nebulised suspension to be administered as either a single dose (Part A) or 11 doses over 6 days (Parts B anc C). Starting dose in Part A to be 1.5mg/mL with planned up to 2 fold increments. Doses in Part B will be selected from Part A. Doses in Part C to be selected from Part B |
| Name | Type | Description |
|---|---|---|
| Ensifentrine | DRUG | Delivered twice daily by oral inhalation via a standard jet nebulizer |
| Placebo | OTHER | Placebo matched to ensifentrine delivered twice daily by oral inhalation via a standard jet nebulizer |
| Standard of Care (SOC) | DRUG | Background treatment of LAMA/LABA/ICS or LAMA/LABA (if ICS is not appropriate) administered per product approved label delivered by oral inhalation as part of standard of care |
| Ensifentrine 3 mg | DRUG | Single dose, administered by oral inhalation using a standard jet nebulizer |
| Glycopyrrolate 42.5 mcg | DRUG | Single dose, administered by oral inhalation using a standard jet nebulizer |
| Ensifentrine 1.5 mg | DRUG | Single dose, administered by oral inhalation using a standard jet nebulizer |
| Ensifentrine 3 mg (marketed formulation) | DRUG | Single dose, administered by oral inhalation using a standard jet nebulizer |
| Glycopyrrolate 21.25 mcg | DRUG | Administered by a standard jet nebulizer, twice daily for 28 consecutive days |
| Nebulized Ensifentrine Suspension; 3 mg | DRUG | Administered by a standard jet nebulizer, twice daily up to a maximum of 52 weeks |
| Nebulized Placebo Solution | DRUG | Administered by a standard jet nebulizer, twice daily up to a maximum of 52 weeks |
| Part A: RPL554 | DRUG | Single dose RPL554 via metered dose inhaler. |
| Placebos | DRUG | Part A: Single dose placebo via metered dose inhaler. Part B: Repeat doses of placebo via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days. |
| Part B: RPL554 | DRUG | Part B: Repeat doses via metered dose inhaler in crossover fashion. One dose administered twice daily over 7 days. |
| RPL554 Suspension | DRUG | A PDE3/4 inhibitor |
| Tiotropium/olodaterol (Respimat) | DRUG | An anticholinergic/β-agonist combination medication |
| RPL554 | DRUG | RPL554 suspension administered using a nebuliser |
| 1.5 mg RPL554 plus tiotropium | DRUG | - |
| 6 mg RPL554 plus tiotropium | DRUG | - |
| Placebo plus tiotropium | DRUG | - |
| Salbutamol | DRUG | a beta-2 receptor agonist |
Inclusion Criteria: Inclusion Criteria include but are not limited to: * Has a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) that was made ≥12 months prior to randomization * Has been on the stable treatment with the same standard of care (SOC) with long-acting muscarinic antagonist (L...
Ensifentrine is an investigational inhaled small molecule developed by Merck & Company, Inc. (ticker MRK) for respiratory disease. It is being studied in chronic obstructive pulmonary disease (COPD) and non-cystic fibrosis bronchiectasis. It is a nebulized suspension given in a 3 mg dose and is also known as MK-5884 and RPL554.
Ensifentrine targets the phosphodiesterase enzymes PDE3A, PDE3B, PDE4A, PDE4B, PDE4C, and PDE4D. It acts as an inhibitor of these PDE3 and PDE4 subtypes, a dual mechanism intended to combine bronchodilator and anti-inflammatory activity within a single inhaled molecule.
Ensifentrine is being developed for chronic obstructive pulmonary disease, including prevention of COPD exacerbations in adults with a history of moderate or severe exacerbations while on standard of care. It is also in development for non-cystic fibrosis bronchiectasis. It remains investigational and is not established as an approved therapy.
Ensifentrine is developed by Merck & Company, Inc., which trades under the ticker MRK. The program is identified in trial records as MK-5884 and RPL554, and a fixed-dose combination with glycopyrrolate is designated MK-5884A.
Ensifentrine is in Phase 2 development overall, with completed Phase 2 studies in COPD and a recruiting Phase 2 study in non-cystic fibrosis bronchiectasis. A Phase 3 COPD exacerbation trial, ENHANCE-3, is registered and not yet recruiting. Ensifentrine is investigational and is not an approved product.
Registered trials include NCT07874815, a Phase 3 COPD exacerbation prevention study not yet recruiting; NCT07132983, a completed Phase 2 pharmacokinetic study of ensifentrine-glycopyrrolate; NCT07016412, a completed Phase 2 fixed-dose combination dose-ranging study; and NCT06559150, a recruiting Phase 2 bronchiectasis study.
Yes. Ensifentrine is also known as MK-5884 and RPL554, and the fixed-dose combination with glycopyrrolate is called MK-5884A. The nebulized 3 mg suspension is the inhaled formulation studied in the COPD and bronchiectasis trials, so searches for these names refer to the same asset.