Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05426915 |
| Other study ID # |
2022-ROFDAM-EL-161 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2023 |
| Est. completion date |
May 1, 2024 |
Study information
| Verified date |
September 2023 |
| Source |
Elpen Pharmaceutical Co. Inc. |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Preferred pharmacological management for COPD according to the GOLD guidelines are the
long-acting anticholinergic LAMAs (Long-Acting / Short-Acting Muscarinic Antagonists), and
long-acting β 2-Agonists LABA (Long-acting LABA) / β2-Long Action Fighters) as well as
inhaled corticosteroids (ICS) Other drugs that can be used besides long-acting, are
short-acting anticholinergics (SAMA) and β2-agonists (SABA), methylxanthines (Aminophylline
and Theophylline), mucolytics and phosphodiesterase inhibitors 4 (Phosphorus) of which is
roflumilast
Description:
Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor, a non-steroidal, anti-inflammatory
active substance intended to target both systemic inflammation and COPD-related lung
inflammation. The mechanism of action is the inhibition of PDE4, which is an important enzyme
for the metabolism of cyclic adenosine monophosphate (cAMP) found in structural and
inflammatory cells, which are important in the pathogenesis of COPD. Roflumilast targets
PDE4A, 4B and 4D subtypes with similar activity in the nanomolecular range. The affinity for
PDE4C subtypes is 5 to 10 times lower. This mechanism of action and selectivity also apply to
roflumilast N-oxide, which is the main active metabolite of roflumilast. Inhibition of PDE4
leads to increased levels of intracellular cAMP and attenuates COPD-related dysfunctions of
leukocytes, smooth muscle cells of the airways and lungs, endothelial cells and epithelial
cells and epithelial cells. In vitro stimulation of human neutrophils, monocytes, macrophages
or lymphocytes, roflumilast and roflumilast N-oxide suppress the release of inflammatory
mediators e.g. leukotriene B4, reactive oxygen species, tumor necrosis factor α, interferon γ
and granzyme B.
In patients with COPD, roflumilast reduced neutrophils in the sputum. In addition, it
mitigated the influx of neutrophils and eosinophils into the airways of healthy volunteers
following endotoxin challenge. Studies using roflumilast have shown that there has been a
statistically significant and clinically significant reduction in exacerbations in COPD
patients. Depending on the study, a reduction ranging from 15% -37% was observed. In 2
placebo-controlled 12-month roflumilast studies, where 50% of patients were on maintenance
therapy with a LABA, the reduction in exacerbations was 17% (P <0.001) (12). Also, in 2
studies of roflumilast for 6 months, controlled with placebo, the reduction of exacerbations
when taken with salmeterol was 37%, P = 0.0315 (post-hoc analysis) or with Tiotropium 23%, P
= 0.196.
The drug of the present study is Damirast 500 mg of which the active substance is
roflumilast. It is a potent selective PDE4 inhibitor with multiple anti-inflammatory actions.
Improves pulmonary function (48-55mL), reduces exacerbations (15-37%)and prolongs the time to
the first exacerbation (up to 40%).
Damirast is indicated for the maintenance treatment of severe chronic obstructive pulmonary
disease (COPD) in addition to bronchodilator therapy, LABA / LAMA and / or inhaled
corticosteroids.
Damirast is an innovative anti-inflammatory treatment specifically designed for COPD patients
with chronic cough and sputum. The anti-inflammatory action of Damirast reduces the incidence
of exacerbations, while it also actively contributes to the improvement of the patient's lung
function, making it the appropriate medication for the long-term treatment of COPD. In
addition, once daily oral administration is expected to play a key role in patient
compliance, as it offers the added benefit of systematic availability and easy access.
Damirast can thus reach even the smallest and most distant bronchi and pulmonary alveoli,
which are often blocked by mucus, making it difficult to exchange gases and prevent the
absorption of inhaled drugs.
