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Ciclesonide/Formoterol Combination

Phase 3

Asthma | Small molecule | Respiratory |AstraZeneca PLC|Last Updated: Apr 26, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDBiomarker
Total Trials19
Total Enrollment6,995
FDA Designations
No designations recorded
Clinical Trials (19)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00392288Efficacy and Safety of Ciclesonide (CIC) Administered Twice Daily in Pediatric Patients With Asthma.PHASE3 COMPLETED 528Sep 1, 2006Feb 1, 2008Feb 1, 20176 United States, Hungary +4
NCT00384189A Comparative Study of Inhaled Ciclesonide Versus Placebo in Children (6-11 Years) With AsthmaPHASE3 COMPLETED 1,080Sep 1, 2006Aug 1, 2008Feb 1, 2017122 Bulgaria, Germany +7
NCT00306163Responsiveness of Lower Airways in Adult Patients (18-60 Years) With Stable Asthma After Treatment With Ciclesonide and Fluticasone Propionate (BY9010/NL-101)PHASE3 COMPLETED 37May 1, 2006Sep 1, 2008Feb 1, 20171 Netherlands
NCT00305461Effect of Ciclesonide on Quality of Life in Patients With Moderate Persistent Asthma (21 to 65 y) (BY9010/AR-101)PHASE3 COMPLETED 101Feb 1, 2006Feb 1, 2008Dec 5, 201612 Argentina
NCT00163449Efficacy and Safety of Ciclesonide in Preschool Children With Asthma (2 to 6 Years) (BY9010/M1-207)PHASE3 COMPLETED 1,000Nov 1, 2005May 1, 2007Dec 8, 201696 Brazil, Germany +7
NCT00163371Effects of Inhaled Ciclesonide Versus Fluticasone Propionate Versus Placebo on Lower Leg Growth in Prepubertal Children With Mild Persistent Asthma (6 to 12 y) (BY9010/M1-208)PHASE3 COMPLETED 28Sep 1, 2005Dec 1, 2005Dec 1, 20161 Denmark
NCT00163436Efficacy and Safety of Ciclesonide Administered With or Without Different Spacers in Patients With Asthma (12 to 75 y) (BY9010/M1-145)PHASE3 COMPLETED 450Sep 1, 2005Jan 1, 2006Nov 30, 201666 Canada, France +4
NCT00163293Efficacy of Ciclesonide Inhaled Once Daily Versus Other Corticosteroids Used for Treatment of Mild Asthma in Children (4 to 11 Years) (BY9010/CA-101)PHASE3 COMPLETED 240Jan 1, 2005Apr 1, 2010Apr 26, 20177 Canada, Hungary +1
NCT00163319Efficacy of Ciclesonide and Fluticasone Propionate in Adult Patients With Moderate and Severe Persistent Asthma (18 to 75 y) (BY9010/IT-101)PHASE3 COMPLETED 500Nov 1, 2004Nov 1, 2005Dec 2, 201689 Belgium, France +5
NCT00163423Efficacy of Ciclesonide Versus Fluticasone Propionate in Patients With Mild to Moderate Asthma (12 to 75 y) (BY9010/M1-142)PHASE3 COMPLETED 480Nov 1, 2004Jan 1, 2006Dec 8, 201651 Austria, Canada +3
NCT00163462Efficacy of Ciclesonide Inhaled Once Daily Versus Fluticasone Propionate Inhaled Twice Daily in Children With Asthma (6 to 11 y) (BY9010/M1-206)PHASE3 COMPLETED 750Oct 1, 2004Nov 1, 2005Dec 5, 201657 Brazil, Germany +4
NCT00163397Efficacy of Ciclesonide Versus Budesonide in Patients With Asthma (18 to 75 y) (BY9010/M1-137)PHASE3 COMPLETED 120Jan 1, 2004Jul 1, 2005Nov 30, 20166 Malaysia, Taiwan
NCT00163384Effectiveness of Ciclesonide Versus Budesonide in Patients With Asthma (18 to 75 y) (BY9010/M1-136)PHASE3 COMPLETED 240Jan 1, 2004May 1, 2005Nov 30, 201619 South Korea
NCT00163358Efficacy of Ciclesonide vs Fixed Combination of Fluticasone Propionate/Salmeterol vs Placebo in Patients With Mild Persistent Asthma (12 to 75 y) (BY9010/M1-132)PHASE3 COMPLETED 630Sep 1, 2003Oct 1, 2005Nov 30, 2016111 Australia, Canada +5
NCT00163345Efficacy of Ciclesonide on Small Airways in Patients With Stable Asthma (18 to 60 y) (BY9010/M1-131)PHASE3 COMPLETED 20Sep 1, 2003May 1, 2006Dec 8, 20161 Netherlands
NCT00163410Efficacy of Ciclesonide Inhaled Once Daily Versus Fluticasone Propionate Inhaled Twice Daily in Children With Asthma (4 to 15 y) (BY9010/M1-205)PHASE3 COMPLETED 500Apr 1, 2003Dec 1, 2004Dec 2, 201616 India
NCT00163332Effect of Inhaled Ciclesonide Versus Fluticasone Propionate in Patients With Mild to Moderate Asthma (18 to 65 y) (BY9010/M1-129)PHASE3 COMPLETED 30Mar 1, 2003 -Dec 6, 20165 Belgium
NCT00546520Effect of Inhaled Ciclesonide in Adult Patients With Asthma (BY9010/M1-125)PHASE3 COMPLETED 21Apr 1, 2002Jun 1, 2002Dec 7, 20161 United Kingdom
NCT00314509Safety and Tolerability of Ciclesonide and Formoterol Fumarate Inhaled Once Daily in Patients With Asthma (18 to 75 y) (BY9010/M1-506)PHASE2 COMPLETED 240Jul 1, 2005Jan 1, 2006Dec 5, 201626 France, Germany +2
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Study Endpoints
Primary Endpoints
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 12.
Baseline and Week 12

Change in FEV1 (Percent of predicted) from baseline to week 12. FEV1 was measured only in children between 6 to \<12 years only. Least Squares Mean were adjusted for Baseline FEV1, age \[yrs\], pooled center, previous corticosteroid therapy and holding chamber.

Change From Baseline in Morning Peak Expiratory Flow (PEF)
Baseline and Week 12

PEF is the maximum speed of expiration. A portable electronic PEF meter was used for the home PEF readings. The patients recorded PEF daily, in the morning immediately after getting up. Readings were done preferably at least 4 hours after use of rescue medication and before inhalation of the study medication. At each measurement, three readings were obtained in the standing position. All three values were recorded in the diary; the highest value was used for evaluation. The higher change from Baseline values are the best. Analysis of covariance (ANCOVA) model with the baseline value and age as covariates was used for analysis. Last observation carried forward.

PC20 AMP (Post-treatment Compared to Baseline)
Baseline and 5 weeks

Mean change of Provocative concentration of Adenosine-5'-monophosphate (PC20 AMP) leading to a 20 percent decrease in Forced expiratory volume in one second (FEV1) between post-treatment and baseline using two different particle sizes. - Small particles = Mass mean aerodynamic diameter (MMAD) of approximately 1.04-1.08 micron - Large particles = MMAD of approximately 9.9-10.6 micron

differences in Quality of Life from AQLQ(S) (T end versus T0)
8 weeks
time to first exacerbation
8 weeks
differences in FEV1 and FVC from spirometry (T end vs T0).
8 weeks
time to first moderate or severe asthma exacerbation.
24 weeks
growth velocity of the right lower leg as measured by knemometry.
FEV1.
Time to First Asthma Exacerbation
Up to 12 months

Time to first asthma exacerbation is defined as the time in days until the first asthma exacerbation, or to the end of treatment visit. In the absence of an exacerbation, an early treatment discontinuation is treated as a censored observation on the day following the last use of study drug.

Exacerbations (Post-hoc Analysis of Annual Rates)
Up to 12 months

A model-based analysis of asthma exacerbation was performed to adjust to important covariables. The distribution of the data suggested a Poisson regression modeling (zero inflated) strategy. After a variable selection process considering also variable-by-treatment interactions, the variables centre, age \[years\] and race were identified to be important beside treatment. The parameters centre and age \[years\] were allocated to zero-model part and the variables treatment and race to the Poisson model part. The estimates of the per-treatment rates are based on a negative-binomial distribution.

number of patients with candidiasis of the oropharynx or hoarseness.
FEV1
time to the first asthma exacerbation.
FEV1 absolute values
PD20FEV1 from methacholine challenge.
FEV1 absolute values.
time until the first severe asthma exacerbation occurs
number of poorly controlled asthma days.
variables of primary interest are FVC% at PC20 MCh, SVC% at PC20 MCh
FVC% at PC20 AMP, SVC% at PC20 AMP
regional air trapping
bronchial and alveolar exhaled NO
lung function variables
non-cellular inflammatory markers.
AUC(0-24h)/24 h of serum cortisol level
24 h urinary cortisol excretion adjusted for creatinine.
PC20FEV1 (AMP)
Time to the first experience of lack of efficacy
AUC (FEV1) over a 24 h dosing interval.
Secondary Endpoints
Change From Baseline in Total Daily Asthma Symptom Score at Week 12.
Baseline and Week 12
Change From Baseline in Use of Albuterol/Salbutamol at Week 12.
Baseline and Week 12
Time to First Event of Lack of Efficacy (LOE) by Week 12
12 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Placebo MDIPLACEBO_COMPARATORdouble-blind
Ciclesonide MDI 40 µg BIDEXPERIMENTALdouble-blind
Ciclesonide MDI 80 µg BIDEXPERIMENTALdouble-blind
Ciclesonide 40 µgACTIVE_COMPARATORPlacebo-matching ciclesonide, inhaled via a metered-dose inhaler (MDI) with 1,1,1,2-hydrofluoroalkane (HFA)-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 40 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
Ciclesonide 80 µgACTIVE_COMPARATORPlacebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 80 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
Ciclesonide 160 µgACTIVE_COMPARATORPlacebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily, in the evening for 2 to 4 weeks in the Baseline period followed by ciclesonide 160 µg, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
PlaceboPLACEBO_COMPARATORPlacebo-matching Ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 2 to 4 week in the Baseline period followed by placebo-matching ciclesonide, inhaled via a MDI with HFA-134a as propellant, once daily in the evening for 12 weeks. Salbutamol 100 μg/puff was available to be used as rescue medication if needed.
1ACTIVE_COMPARATORCiclesonide 160 µg
2ACTIVE_COMPARATORFluticasone 100 µg
3ACTIVE_COMPARATORCiclesonide 160 µg
4PLACEBO_COMPARATORPlacebo
Ciclesonide 100 µgACTIVE_COMPARATORCiclesonide 100 µg, metered-dose inhaler, two puffs once daily, in the evening, for up to 12 months.
Ciclesonide 200 µgACTIVE_COMPARATORCiclesonide 200 µg, metered-dose inhaler, two puffs once daily, in the evening, for up to 12 months.
Interventions
NameTypeDescription
CiclesonideDRUGCiclesonide MDI 40 µg BID over twelve weeks
PlaceboDRUGPlacebo MDI over twelve weeks
SalbutamolDRUGSalbutamol inhalation powder
FluticasoneDRUGinhaled Fluticasone 100 µg, twice daily
Ciclesonide/Formoterol CombinationDRUG -
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Eligibility Criteria
Age Range4 Years — 11 Years
SexALL
Healthy VolunteersNo
Study Sites6

Inclusion Criteria: * History of persistent bronchial asthma for at least 3 months prior to screening; * For patients with persistent bronchial asthma and being treated with a controller therapy: Documented use of an inhaled steroid or Singulair® 5mg once daily; * For patients with persistent bronc...

Countries:United StatesHungaryMexicoPolandRussiaSouth AfricaBulgariaGermanyRomaniaSpainUkraineNetherlandsArgentinaBrazilIndiaSwitzerlandDenmarkCanadaFranceItalyBelgiumUnited KingdomAustriaPortugalMalaysiaTaiwanSouth KoreaAustraliaCzechia
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