Allergic AsthmaPhase 2NCT01365533
A Study to Evaluate the Effect of Roflumilast on Airway Inflammation and Function Following Allergen Challenge in Subjects With Allergic Asthma
A Phase 2 study testing Roflumilast in people with Allergic Asthma, run by AstraZeneca at 1 site in Canada.
Trial summary
The study was a double-blind, placebo-controlled, crossover study to evaluate the efficacy of roflumilast on airway inflammation and function in patients with allergen-induced asthma. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Allergic Asthma
- What is being tested?
- Roflumilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2004to Jul 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- the patient was an outpatient
- had to have a negative (quantitative) serum pregnancy test for female patients of childbearing potential at Phase 1 Screening (Visit 1), a negative urine pregnancy test for female patients of childbearing potential at Phase 3 Randomization/Treatment Period 1 (Visit 5) and Phase 4 Treatment Period 2/Final Evaluation (Visit 9) prior to double-blind treatment
- had symptoms of asthma for the last 6 months that satisfied the American Thoracic Society (ATS) definition of asthma,i.e. episodic wheezing, coughing, shortness of breath, and chest tightness associated with airflow limitation that was at least partially reversible, either spontaneously, or with medication
- had an unmedicated (no inhaled short-acting bronchodilator for at least 8 hours) FEV1 ≥70 percent of the predicted normal value for age, height, and sex, with a 12 percent downward adjustment applied for individuals of African descent
- positive Methacholine (MCh) inhalation challenge at Pre-Randomization Evaluation Visit 2 [provocative concentration resulting in a 20 percent reduction in FEV1 (MCh PC20FEV1) <16 mg/mL] reflecting AHR
- had a documented allergy to a common aeroallergen (animal, dust mite, mold, and pollen allergens) as confirmed by a recognized skin prick test wheal ≥2 mm in diameter.
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- positive allergen-induced early and late airway bronchoconstriction. The EAR was defined by an acute fall in FEV1 ≥20 percent within 2 hours following allergen challenge. The LAR was defined by a fall in FEV1 ≥15 percent between 3 hours and 7 hours following allergen challenge
- the patient was someone from whom the investigator or study personnel would expect conscientious cooperation over the duration of the study
- the patient was able to execute or obtain written informed consent at Visit 1.
Who cannot join
- current neuropsychiatric condition with or without drug therapy that was judged by the investigator to be clinically significant and/or affect the patient's ability to participate in the clinical study. Such as having a history of Attention Deficit/Hyperactivity Disorder (ADHD) that was considered unstable by the investigator, and if pharmacotherapy was required, i.e. Ritalin®, Adderall®, patient had to be on pharmacotherapy for ≥1 month prior to Visit 1. The pharmacotherapeutic regimen had to remain stable during the conduct of the study
- had a history of learning disabilities or intellectual impairment that in the opinion of the investigator prevented the patient from participating in the study
- impairment of hepatic function including alcohol related liver disease, cirrhosis, or hepatitis, cancer, or any clinically significant hematologic, renal, endocrine (except for controlled diabetes mellitus, post-menopausal symptoms, or hypothyroidism), cardiovascular (particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure), neurologic (including transient ischemic attack, stroke, seizure disorder, migraine headache), or gastrointestinal disease
- clinically significant abnormalities in physical examination and/or in laboratory test results (including hematology and chemistry panels, urinalysis) as assessed by the investigator. The patient was not allowed to have an abnormality detected on physical or laboratory examination considered to be clinically significant by the investigator and limiting to the study's conduct unless the abnormality was related to underlying asthma
- worsening of asthma (requiring daily use of nebulized Beta2-agonists or any use of long-acting Beta-agonists (LABA), or requiring inpatient hospitalization for asthma control, or requiring emergency room treatment, or requiring systemic corticosteroids for asthma control) or respiratory infection in the 6 weeks preceding the Screening Visit
- use of inhaled (>1 mg beclomethasone dipropionate [BDP]-equivalents/day) or systemic (intramuscular, intravenous, or oral) corticosteroids within 60 days prior to Screening and Pre-Randomization Evaluation visits
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- use of nasal or inhaled corticosteroids (≤1 mg BDP-equivalents/day), intraophthalmic corticosteroids, nasal, inhaled, or intraophthalmic cromolyn sodium or nedocromil, leukotriene receptor antagonists (zafirlukast,pranlukast, montelukast), and 5-lipoxygenase inhibitors (zileuton) within 4 weeks prior to Screening and Pre-Randomization Evaluation visits. Topical corticosteroids for dermatologic use were allowed
- use of anti-immunoglobulin E (IgE) therapy or immunosuppressives within 3 months prior to Screening and Pre-Randomization Evaluation visits
- use of any immunotherapy within 3 months prior to Screening and Pre-Randomization Evaluation visits
- use of oral and intra-ophthalmic nonsteroidal anti-inflammatory agents (NSAIDs) was permitted, but not within 48 hours of Pre-Randomization Evaluation spirometry. Aspirin® use was not permitted within 7 days of Pre-Randomization Evaluation spirometry
- theophylline-containing agents of any type, LABA (salmeterol, formoterol), and long-acting anticholinergics (tiotropium) were not permitted within 1 week prior to Screening and Pre-Randomization Evaluation visits. Short-acting inhaled Beta2-agonists and inhaled short-acting anticholinergics could be used intermittently according to individual needs, however, they were to be withheld at least 8 hours before the conduct of any challenge or spirometry
- use of oral, intranasal, intra-ophthalmic anti-histamines within 5 days prior to Screening and Pre-Randomization Evaluation visits
- use of caffeine-containing products (such as chocolate, tea, caffeinated sodas) or medications (such as combination products with caffeine, including butalbitalcodeineacetominophen-caffeine, butalbital-acetominophen-caffeine, dihydocodeineacetominophen-caffeine, ergotamine-caffeine, hydrocodone-chlorpheniraminephenylephrineacetominophen-caffeine) for 12 hours, or alcohol or over the counter drugs including cold and allergy medications for 48 hours, or inhaled bronchodilators for 8 hours prior to Screening and Pre-Randomization Evaluation MCh and allergen challenges or spirometry
- herbal supplements and nutraceuticals were not permitted. However, vitamins were allowed
- patient was a smoker (including cigarettes, cigars, pipe, chewing tobacco, or cannabis, i.e. hashish, marijuana). Patients were not allowed to have a history of smoking within the past year and a total smoking history of ≥2 pack-years
- lung disease other than mild to moderate asthma
- concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment could interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease
- recent (<1 year) history of alcohol dependency
- unable and/or unlikely to comprehend and/or follow the protocol over the duration of the study
- participation in any other studies involving investigational or marketed products within 30 days prior to entry into the study
- had donated blood or blood products for transfusion during the 1 month prior to initiation of treatment with study drug, and at any time during the study
- surgery of gastrointestinal tract which could interfere with drug absorption (Note: This was not applicable for minor abdominal surgery such as appendectomy or herniorrhaphy)
- other severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or investigational product administration or could interfere with the interpretation of study results and, in the judgment of the investigator, could make the patient inappropriate for entry into this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of Roflumilast on Airway Inflammation and Function Following Allergen Challenge in Subjects With Allergic Asthma
The study was a double-blind, placebo-controlled, crossover study to evaluate the efficacy of roflumilast on airway inflammation and function in patients with allergen-induced asthma.
Individuals with stable, mild to moderate allergic asthma, with a history of episodic wheeze and shortness of breath, were eligible for enrollment.
- Conditions
- Allergic Asthma
- Being tested
- Roflumilast, Placebo
- Keywords
- Airway Inflammation, Roflumilast
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoflumilastDrug
Roflumilast 500 μg, one tablet once daily, orally
PlaceboDrug
Placebo, one tablet once daily, orally
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast | Active comparator | Not described Receives: Drug: Roflumilast |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of percent eosinophils in sputum 24 hours after allergen challenge
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).
Measured: From baseline until end of treatment up to 9 weeks
Secondary outcomes (2)
To evaluate the allergen-induced Early asthmatic response (EAR) and Late asthmatic response (LAR) in patients with allergic asthma following repeated dosing of roflumilast
- Allergen-induced EAR as measured by Forced expiratory volume in 1 second (FEV1) within 2 hours after allergen challenge, between roflumilast and placebo (Area under the curve [AUC] and maximal drop)
- Allergen-induced LAR as measured by FEV1 in the period beginning 3 hours and ending 7 hours after allergen challenge, between roflumilast and placebo (AUC and maximal drop)
Measured: From baseline until end of treatment up to 9 weeks
To evaluate the effect of roflumilast on allergen-induced Airway hyperreactivity (AHR)
Allergen-induced AHR at 24 hours post-allergen, as measured by the Methacholine provocative concentration resulting in a 20 percent reduction in FEV1 (MCh PC20FEV1) and as Doubling concentration factor (DC) required to achieve a decrease in FEV1 of 20 percent, between roflumilast and placebo
Measured: From baseline until end of treatment up to 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2011 (estimated)
- Study startDec 2004
- Primary completionJul 2005
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Allergic AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AstraZeneca AstraZeneca, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01365533
- Sponsor's protocol ID
- BY217/M2-034
- Status last verified
- Sep 2016
- First submitted
- 30 May 2011
- Last updated
- 25 Oct 2016
- Results posted
- No
Publications
Bardin P, Kanniess F, Gauvreau G, Bredenbroker D, Rabe KF. Roflumilast for asthma: Efficacy findings in mechanism of action studies. Pulm Pharmacol Ther. 2015 Dec;35 Suppl:S4-10. doi: 10.1016/j.pupt.2015.08.006. Epub 2015 Aug 19.
PubMed 26296794Gauvreau GM, Boulet LP, Schmid-Wirlitsch C, Cote J, Duong M, Killian KJ, Milot J, Deschesnes F, Strinich T, Watson RM, Bredenbroker D, O'Byrne PM. Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects. Respir Res. 2011 Oct 26;12(1):140. doi: 10.1186/1465-9921-12-140.
PubMed 22029856
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of Roflumilast on Airway Inflammation and Function Following Allergen Challenge in Subjects With Allergic Asthma
- ClinicalTrials.gov ID
- NCT01365533
- Acronym / sponsor ID
- BY217/M2-034
- Conditions
- Allergic Asthma
- Keywords
- Airway Inflammation, Roflumilast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Dec 2004
- Primary completion
- Jul 2005 (actual)
- Study completion
- Jul 2005 (actual)
- First posted
- 3 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study was a double-blind, placebo-controlled, crossover study to evaluate the efficacy of roflumilast on airway inflammation and function in patients with allergen-induced asthma.
Individuals with stable, mild to moderate allergic asthma, with a history of episodic wheeze and shortness of breath, were eligible for enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roflumilast | Active comparator | Drug: Roflumilast |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- the patient was an outpatient
- had to have a negative (quantitative) serum pregnancy test for female patients of childbearing potential at Phase 1 Screening (Visit 1), a negative urine pregnancy test for female patients of childbearing potential at Phase 3 Randomization/Treatment Period 1 (Visit 5) and Phase 4 Treatment Period 2/Final Evaluation (Visit 9) prior to double-blind treatment
- had symptoms of asthma for the last 6 months that satisfied the American Thoracic Society (ATS) definition of asthma,i.e. episodic wheezing, coughing, shortness of breath, and chest tightness associated with airflow limitation that was at least partially reversible, either spontaneously, or with medication
- had an unmedicated (no inhaled short-acting bronchodilator for at least 8 hours) FEV1 ≥70 percent of the predicted normal value for age, height, and sex, with a 12 percent downward adjustment applied for individuals of African descent
- positive Methacholine (MCh) inhalation challenge at Pre-Randomization Evaluation Visit 2 [provocative concentration resulting in a 20 percent reduction in FEV1 (MCh PC20FEV1) <16 mg/mL] reflecting AHR
Key exclusion criteria (23 listed)
- current neuropsychiatric condition with or without drug therapy that was judged by the investigator to be clinically significant and/or affect the patient's ability to participate in the clinical study. Such as having a history of Attention Deficit/Hyperactivity Disorder (ADHD) that was considered unstable by the investigator, and if pharmacotherapy was required, i.e. Ritalin®, Adderall®, patient had to be on pharmacotherapy for ≥1 month prior to Visit 1. The pharmacotherapeutic regimen had to remain stable during the conduct of the study
- had a history of learning disabilities or intellectual impairment that in the opinion of the investigator prevented the patient from participating in the study
- impairment of hepatic function including alcohol related liver disease, cirrhosis, or hepatitis, cancer, or any clinically significant hematologic, renal, endocrine (except for controlled diabetes mellitus, post-menopausal symptoms, or hypothyroidism), cardiovascular (particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure), neurologic (including transient ischemic attack, stroke, seizure disorder, migraine headache), or gastrointestinal disease
- clinically significant abnormalities in physical examination and/or in laboratory test results (including hematology and chemistry panels, urinalysis) as assessed by the investigator. The patient was not allowed to have an abnormality detected on physical or laboratory examination considered to be clinically significant by the investigator and limiting to the study's conduct unless the abnormality was related to underlying asthma
- worsening of asthma (requiring daily use of nebulized Beta2-agonists or any use of long-acting Beta-agonists (LABA), or requiring inpatient hospitalization for asthma control, or requiring emergency room treatment, or requiring systemic corticosteroids for asthma control) or respiratory infection in the 6 weeks preceding the Screening Visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RoflumilastRoflumilast 500 μg, one tablet once daily, orally | Drug | Roflumilast |
| PlaceboPlacebo, one tablet once daily, orally | Drug | Placebo |
Primary outcome
Change of percent eosinophils in sputum 24 hours after allergen challenge
Time frame: From baseline until end of treatment up to 9 weeks
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).
2 secondary outcomes
To evaluate the allergen-induced Early asthmatic response (EAR) and Late asthmatic response (LAR) in patients with allergic asthma following repeated dosing of roflumilast
Time frame: From baseline until end of treatment up to 9 weeks
To evaluate the effect of roflumilast on allergen-induced Airway hyperreactivity (AHR)
Time frame: From baseline until end of treatment up to 9 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2016.
- Derived from this study: PubMed 26296794Bardin P, Kanniess F, Gauvreau G, Bredenbroker D, Rabe KF. Roflumilast for asthma: Efficacy findings in mechanism of action studies. Pulm Pharmacol Ther. 2015 Dec;35 Suppl:S4-10. doi: 10.1016/j.pupt.2015.08.006. Epub 2015 Aug 19.
- Derived from this study: PubMed 22029856Gauvreau GM, Boulet LP, Schmid-Wirlitsch C, Cote J, Duong M, Killian KJ, Milot J, Deschesnes F, Strinich T, Watson RM, Bredenbroker D, O'Byrne PM. Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects. Respir Res. 2011 Oct 26;12(1):140. doi: 10.1186/1465-9921-12-140.
- BY217-M2-034-RDS-2007-06-05.pdfLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AstraZeneca AstraZeneca study director
AstraZeneca
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Roflumilast in people with Allergic Asthma, run by AstraZeneca at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of percent eosinophils in sputum 24 hours after allergen challenge (time frame: From baseline until end of treatment up to 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01365533, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2016.