Clinical trial NCT01365533 (phase 2, status: completed)
Conditions: allergic asthma
ICD codes: D69.0, L50.0, B44.81, J30.89, J30.9, L20.84, H10.45
Drugs: roflumilast, placebo
SMILES: FC(F)OC1=C(OCC2CC2)C=C(C=C1)C(=O)NC1=C(Cl)C=NC=C1Cl, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  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.

          -  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.

        Exclusion Criteria:

          -  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

          -  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