Efficacy
Think smaller.
For most patients, keeping asthma well controlled means avoiding triggers and using a long-term control medication every day to help reduce airway inflammation.1 When considering an ICS to prescribe, choose Alvesco (ciclesonide) Inhalation Aerosol. It's a long-term asthma control medicine with small particles designed to reach deep into airways. Alvesco delivers medicine where it may help to reduce asthma inflammation.8
Alvesco Inhalation Aerosol is an ICS with a small particle size (~1-2 µm).2,*
This enables Alvesco to reach areas of chronic inflammation in both the large and small airways.2,3
- Aerosol particle size is a key factor in both the extent of lung deposition and the regional distribution within the lung.4
- ICS particle sizes <2 µm in diameter are more likely to reach the small airways – where they can have a targeted effect without as many local adverse effects in the throat and oral cavities as inhalers with larger particle sizes.2,8,12
*Particle size does not necessarily correlate with clinical efficacy
Particle size.
Small particle size means 52% of the delivered Alvesco Inhalation Aerosol dose was deposited in the lungs. 2,*,†,‡
52%
Deposition in Lungs
Representative 2D lung deposition pattern of 99mTC-ciclesonide HFA in an asthmatic patient.
*Based on 2-dimensional (2D) scintigraphy.
†Scintigraphy is not a valid surrogate for clinical effect.
‡Percent deposited dose based on 3-dimensional (3D) single-photon emission computed tomography
imaging of the
regional
distribution of radio-labeled ciclesonide.
HFA = hydrofluoroalkane
Within the lung, most of the Alvesco that was deposited was found in the small airways and alveoli.2,*,†
Study Design: Single-dose,
open-label,
nonrandomized study
performed in 12 patients with
mild asthma. Patients received a single dose of 99mtechnetium (Tc)-ciclesonide HFA 320 mcg ex-actuator
(400 mcg ex-valve). The primary study variable was the total and regional distribution of ciclesonide in the lungs,
oropharynx, and exhaled air.2
*Percent deposited dose based on 3-dimensional (3D) single-photon emission computed tomography imaging of the
regional distribution of radio-labeled ciclesonide.
†The relationship of lung deposition to clinical efficacy is unknown
HFA = hydrofluoroalkane
Alvesco in 3D action.
Favorable pharmacokinetic profile.
Alvesco Inhalation Aerosol offers a low systemic exposure and favorable pharmacokinetic profile. We define systemic exposure as the combination of:1,12
- Pulmonary availability: the dose delivered to the lungs
- Oral bioavailability: the dose delivered to the GI tract
One goal of ICS treatment is to have low oral bioavailability in order to reduce the risk of systemic side effects.12
Ciclesonide is a prodrug that is metabolized to des-ciclesonide after oral inhalation.1 Using a prodrug rather than one with full therapeutic effect may reduce the risk of adverse effects in the oral cavity and throat.12,13
- Des-ciclesonide has anti-inflammatory activity with an affinity for steroid receptors that is 120 times greater than that of the parent compound and 12 times greater than dexamethasone.1,†
- Ciclesonide and des-ciclesonide have negligible oral bioavailability (both <1%) due to low gastrointestinal absorption and high first-pass metabolism.1
- Most of the ciclesonide and des-ciclesonide remain bound to human plasma proteins (average 99% each), with 1% of unbound drug detected in the systemic circulation.1
Ciclesonide demonstrates efficacy in all asthma severities with low systemic effects, in part due to its pharmacokinetic and pharmacodynamic properties.1,12,13
† The clinical significance of these findings is unknown.
Clinical studies.
The efficacy of Alvesco was evaluated in 6 randomized double-blind, placebo-controlled, parallel-group clinical trials in adult and adolescent patients 12 years of age and older with mild persistent-to-severe persistent asthma.1
Primary Efficacy Endpoints1:
- In 4 of the 6 trials, the primary efficacy endpoint was the mean change from baseline in pre-dose FEV1 at endpoint (last observation).
- In one trial, the primary endpoint was the change from baseline in the average of the pre‑dose FEV1 at Weeks 12 and 16.
- In one trial, the primary efficacy endpoint was reduction of oral corticosteroid use.
Secondary efficacy endpoints were asthma symptoms, use of
albuterol
for rescue, AM PEF,
nighttime awakenings, and withdrawal due to asthma worsening.1
FEV1 = forced expiratory volume in one second
AM PEF = morning peak expiratory flow
Alvesco Inhalation Aerosol significantly improved pre-dose FEV1 at 16 weeks, compared to placebo, in patients new to ICS therapy.1,11
Study Design: A multicenter, double-blind, parallel-group, placebo-controlled, 16-week study in subjects who were 12 years old, had a 6-month history of persistent asthma, a forced expiratory volume in 1 second (FEV1) of >60 to <85% predicted, and who were not using an ICS <30 days before study entry. Subjects were randomized to CIC 80 mcg twice daily (CIC80 BID; n=170); CIC160 mcg once daily in the morning (CIC160 QD in the AM; n=173); CIC80 BID for 4 weeks followed by CIC60 QD for 12 weeks (CIC80 BID/CIC160 QD; n=171); or placebo (n=177).
BID = twice daily
QD = once daily
FEV1 = forced expiratory volume in one second
In that same study in patients new to ICS therapy, Alvesco Inhalation Aerosol reduced nighttime awakenings by 66% from baseline.11
Alvesco (ciclesonide) Inhalation Aerosol reduced nighttime awakenings by 66% from
baseline in patients with mild-to-moderate asthma previously treated with a bronchodilator
alone, vs a 48% reduction with placebo.11 LS mean reduction of 0.37 nighttime
awakenings
with Alvesco, baseline=0.56 vs 0.22 with placebo, baseline=0.46 (P=0.0036 vs placebo).11
LS = least squares
Study Design: Randomized,
double-blind, placebo-controlled, parallel-group
study to assess the efficacy of Alvesco, including 80 mcg twice daily, administered for 16 weeks in 708 patients
12 years of age with mild-to-moderate persistent asthma not currently taking ICS therapy. The primary endpoint was
LS mean change from baseline in FEV1 to the average of Week 12 and Week 16, which was significantly
improved vs placebo. Daily albuterol use and total asthma symptom score were key secondary endpoints, and
nighttime awakenings was an additional secondary endpoint (Alvesco 80 mcg BID, n=170; placebo, n=177).11
FEV1 = forced expiratory volume in one second
In a trial of patients previously maintained on other ICSs, Alvesco Inhalation Aerosol maintained or improved pulmonary function (FEV1) in patients switched from other ICSs or low-dose ICS/LABA combination.1,9
Study Design: In this 12-week, multicenter, double-blind, parallel-group study, subjects aged ≥12 years with stable mild-to-moderate persistent asthma were switched at time of randomization from an ICS or an ICS/LABA to Alvesco 80 mcg BID (n=149), Alvesco 160 mcg QD (n=150), or placebo (n=147). Primary endpoint was the change in FEV1 from baseline to Week 12.
