Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
RPL554 · 6 trials · 6 indications
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
Forced expired volume in one second (FEV1) over 8 hours post-dose
FEV1
Blood pressure and pulse rate
Biochemistry, haematology and urinalysis
Continuous heart monitoring
| Arm | Type | Description |
|---|---|---|
| 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 | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Higher Dose RPL554 | EXPERIMENTAL | Single dose of inhaled 6 mg RPL554 |
| Lower dose RPL554 | EXPERIMENTAL | Single dose of inhaled 1.5 mg RPL554 |
| Salbutamol alone | ACTIVE_COMPARATOR | 200 micrograms salbutamol, ipratropium matched placebo and RPL554 matched placebo |
| Salbutamol and RPL554 | EXPERIMENTAL | 200 micrograms salbutamol, ipratropium matched placebo and 6 mg RPL554 |
| Ipratropium | ACTIVE_COMPARATOR | Salbutamol matched placebo, 40 micrograms ipratropium and RPL554 matched placebo |
| Ipratropium and RPL554 | EXPERIMENTAL | Salbutamol matched placebo, 40 micrograms ipratropium and 6 mg RPL554 |
| RPL554 | EXPERIMENTAL | Salbutamol matched placebo, ipratropium matched placebo and 6 mg RPL554 |
| 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 |
|---|---|---|
| RPL554 Suspension | DRUG | A PDE3/4 inhibitor |
| Placebo | DRUG | A placebo solution |
| Tiotropium/olodaterol (Respimat) | DRUG | An anticholinergic/β-agonist combination medication |
| RPL554 | DRUG | RPL554 suspension administered using a nebuliser |
| Salbutamol | DRUG | 200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI) |
| Ipratropium | DRUG | 40 micrograms ipratropium administered using a pMDI |
| Salbutamol matched placebo | DRUG | Placebo pMDI |
| Ipratropium matched placebo | DRUG | Placebo pMDI |
| RPL554 matched placebo | DRUG | Nebulised placebo |
Inclusion Criteria: 1. Written informed consent 2. Male or female aged 40 and 80 years 3. For males, not to donate sperm and either be sexually abstinent or use contraception as specified by the protocol. For females, be of non-childbearing potential or use a highly effective form of contraception ...
RPL554 is an investigational small molecule being developed for respiratory conditions including COPD, asthma, cystic fibrosis, and inflammatory disorders of the respiratory tract. It is currently in Phase 2 clinical development and is not approved by the FDA.
RPL554 is being studied for use in chronic obstructive pulmonary disease (COPD), including moderate COPD. Clinical trials have evaluated its bronchodilator effects when added to other COPD treatments such as tiotropium and tiotropium/olodaterol.
RPL554 is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting Phase 2 clinical trials of the drug for respiratory indications.
RPL554 is in Phase 2 clinical development. All completed trials for the drug are Phase 2 studies, and the drug remains investigational, meaning it has not received FDA approval.
RPL554 has been studied in several Phase 2 trials, including NCT02919995 in cystic fibrosis patients, NCT03028142 in COPD patients on tiotropium, NCT03443414 as a dose-ranging study in COPD, and NCT03673670 in COPD patients on tiotropium/olodaterol. All trials are completed.
RPL554 is not known to have alternative names. It is a distinct investigational small molecule being developed by Merck & Company, Inc. for respiratory conditions.