Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication DALIRESP ® is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. DALIRESP is a selective phosphodiesterase 4 inhibitor indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. FDA label
Also known as Daxas, Daliresp
Roflumilast · 26 trials · 11 indications
The primary endpoint is the percentage of participants prematurely discontinuing study treatment for any reason during the Main Period from Visit 1 (V1) to Last Visit (Vend). Discontinuation is defined as permanently stopping randomized treatment; participants who resume randomized treatment after an interval will not be counted as having discontinued. The analysis used discontinuations occurring during the Main Period, irrespective of whether a participant subsequently entered into the Down-Titration Period.
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Pulmonary function testing was performed using centralized spirometry prior to taking study medication. Change from baseline over 24 weeks of treatment was calculated from a repeated measures analysis of covariance (ANCOVA) model with treatment, baseline value of pre-bronchodilator FEV1, time and a treatment-by-time interaction as independent variables.
Mean change from baseline during the treatment period in pre-bronchodilator FEV1 \[L\]
Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management \[American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005\].
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured using spirometry in accordance with the American Thoracic Society / European Respiratory Society (ATS/ERS) consensus guidelines. An ANCOVA model with treatment sequence, treatment period, and study treatment as fixed factors with Baseline FEV1 measurement as the covariate was used for analysis.
The primary outcome was the effect of roflumilast on allergen-induced airway eosinophilia. Two 15 days treatment periods (14 days with treatment and day 15 without treatment) separated by a washout period (approximately 3 to 5 weeks).
VRM measures the ability to encode and subsequently retrieve verbal information. This task begins with the first presentation phase in which 18 words are shown in turn on the screen. The participant is then asked to recall as many words as possible during the first immediate recall phase. The same 18 words are then shown in a second presentation phase which is followed by a second immediate recall phase. After a delay of approximately 20-30 minutes, a delayed recall stage is completed. The possible range of correct responses is 0 (worst) to 18 (best). Higher number of correct responses in the test indicates a better outcome. A negative change from baseline indicates a worsening of the score.
VRM measures the ability to encode and subsequently retrieve verbal information. This task begins with the first presentation phase in which 18 words are shown in turn on the screen. The participant is then asked to recall as many words as possible during the first immediate recall phase. The possible range of correct responses is 0 (worst) to 18 (best). Higher number of correct responses in the test indicates a better outcome. A negative change from baseline indicates a worsening of the score.
The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.
PK samples at pre-dose, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h and 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h post dose after single dose and at the time points pre-dose, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h and 24h after administration of a repeated dose
| Arm | Type | Description |
|---|---|---|
| Roflumilast 500 μg once daily | EXPERIMENTAL | Roflumilast 500 μg tablets, orally, once daily for 12 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. |
| Roflumilast 500 μg every other day | EXPERIMENTAL | Roflumilast 500 μg, tablets, orally, every other day, and roflumilast placebo-matching tablets, orally, every other day on non-treatment days, for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. |
| Roflumilast 250 μg once daily | EXPERIMENTAL | Roflumilast 250 μg, tablets, orally, once daily for 4 weeks, followed by roflumilast 500 μg, tablets, orally, once daily, for 8 weeks. Any participants not tolerating study treatment will be prematurely discontinued and will receive roflumilast 250 μg, tablets, orally, once daily for 8 weeks. |
| Roflumilast | ACTIVE_COMPARATOR | 500 μg tablet, once daily, oral administration in the morning after breakfast |
| Placebo | PLACEBO_COMPARATOR | tablet, once daily, oral administration in the morning after breakfast |
| 1 | ACTIVE_COMPARATOR | Roflumilast 500 µg |
| 2 | PLACEBO_COMPARATOR | Placebo |
| Roflumilast plus montelukast, then placebo plus montelukast | EXPERIMENTAL | Participants in sequence 1 received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received placebo plus montelukast 10 mg orally once daily for 4 weeks. |
| Placebo plus montelukast, then roflumilast plus montelukast | EXPERIMENTAL | Participants in sequence 2 received placebo plus montelukast 10 mg orally once daily for 4 weeks followed by a 4-week washout period and then received roflumilast 500 μg plus montelukast 10 mg orally once daily for 4 weeks. |
| Sequence 1 (ABDC) | EXPERIMENTAL | Roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period. |
| Sequence 2 (BCAD) | EXPERIMENTAL | Roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period. |
| Sequence 3 (CDBA) | EXPERIMENTAL | Roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period. |
| Sequence 4 (DACB) | EXPERIMENTAL | Roflumilast Dose A tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 1, followed by roflumilast placebo-matching tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 2, followed by roflumilast Dose A tablets, orally, donepezil placebo-matching overencapsulated tablets, orally, and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 3, followed by roflumilast placebo-matching tablets, orally, donepezil 10 mg, overencapsulated tablets, orally and scopolamine 0.5 mg subcutaneous injection, once, Day 1, Period 4. Each treatment period is separated by a 14-day washout period. |
| Roflumilast + alogliptin | EXPERIMENTAL | Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days. |
| Alogliptin alone | EXPERIMENTAL | Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days. |
| Roflumilast alone | EXPERIMENTAL | Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days. |
| Exenatide | ACTIVE_COMPARATOR | Exenatide 5 μg subcutaneous injection twice a day for 11 days. |
| Name | Type | Description |
|---|---|---|
| Roflumilast | DRUG | Roflumilast tablets |
| Roflumilast Placebo | DRUG | Roflumilast placebo-matching tablets |
| Standard of Care COPD Treatment | DRUG | The participant is on standard of care COPD maintenance treatment including LABAs, long-acting anticholinergics, or any combination thereof taken on a constant daily dose within 12 weeks prior to Screening (Visit V0) Examples of LABA containing products are: Formoterol, Salmeterol, Indacaterol, Formoterol/Budesonide, Salmeterol/Fluticasone, Treatment including lon-acting anticholinergics: Tiotropium, Aclidinium. |
| Placebo | DRUG | tablet, once daily, oral administration in the morning after breakfast |
| Salbutamol | DRUG | Salbutamol (given by MDI and spacer) used as rescue medication on an ass needed basis throughout the trial, and was used for post-bronchodilator spirometry tests at all study visits. |
| Montelukast | DRUG | Montelukast was supplied in tablets. |
| Donepezil | DRUG | Donepezil overencapsulated tablets |
| Donepezil placebo | DRUG | Donepezil placebo-matching overencapsulated tablets |
| Scopolamine | DRUG | Scopolamine subcutaneous injection |
| Alogliptin | DRUG | Alogliptin tablets |
| Exenatide | DRUG | Exenatide solution |
| Placebo to roflumilast | DRUG | Placebo-matching roflumilast tablets |
| Placebo to alogliptin | DRUG | Placebo-matching alogliptin tablets |
Inclusion Criteria: 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any requi...
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| Novartis AG Sponsored ADR | NVS | 5 | PHASE3 | QVM149, QMF149, Glycopyrronium bromide |
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Roflumilast is a small molecule drug developed by AstraZeneca PLC (ticker AZN) for respiratory conditions including chronic obstructive pulmonary disease (COPD), asthma, and allergic asthma. It is a phosphodiesterase 4 (PDE4) inhibitor that is given orally and has been studied in multiple clinical trials.
Roflumilast is used for chronic obstructive pulmonary disease (COPD) to reduce inflammation in the airways. It has been evaluated as an add-on to standard COPD treatment, including a Phase 3 trial (NCT02165826) in patients with severe COPD. It is also being studied in asthma.
Roflumilast targets the phosphodiesterase 4 (PDE4) enzyme family, specifically the subtypes PDE4A, PDE4B, PDE4C, and PDE4D. By inhibiting these enzymes, roflumilast increases intracellular cyclic AMP (cAMP) levels, which helps reduce inflammation in conditions such as COPD and asthma.
Roflumilast is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is a global pharmaceutical company that discovers, develops, and commercializes prescription medicines, including those for respiratory diseases.
Roflumilast is in Phase 2 clinical development for asthma and allergic asthma, according to the current pipeline. It has also been studied in Phase 3 for COPD and in Phase 1 for other conditions. It is an investigational drug and has not been approved by the FDA for these indications.
Roflumilast has been studied in several completed clinical trials, including NCT02165826 (Phase 3 in severe COPD), NCT01765192 (Phase 2 in severe asthma with montelukast), NCT02051335 (Phase 1 in healthy adults for cognitive deficits), and NCT01664624 (Phase 1 in type 2 diabetes). All are completed.