Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 6-month Randomized, Double-blind, Parallel-group, Multicentre, Placebo-controlled Phase II Study to Compare Anti-asthmatic Effect and Safety of Esomeprazole (Nexium®) 40 mg Twice Daily or 40 mg Once Daily With Placebo in Adults With Asthma
Brief Summary: The purpose of this study is to determine whether treatment with esomeprazole for 6 months will improve asthma in adult patients with moderate to severe asthma and symptoms of gastroesophageal reflux disease.


Options:
A: Inclusion Criteria:

* Physician-diagnosed asthma
* At least one of the following lung function criteria must be documented in the year prior to study entry:

  1. Bronchial hyperresponsiveness confirmed by 12% or greater improvement in amount of air expired in first second during a forced expiratory maneuver (FEV1) post-bronchodilator, or
  2. Methacholine post-diluent baseline (PC20) less than 16 mg/ml, or
  3. Exercise bronchoprovocation test with at least a 20% decrease in FEV1
* Currently on stable dose of daily inhaled corticosteroid for asthma control (i.e., inhaled corticosteroid equivalent to 2 puffs of 44 ug twice per day \[176 ug\] of fluticasone or greater for 8 weeks or longer prior to study entry)
* Poor asthma control as defined by any one of the following criteria:

  1. Use of beta-agonist for asthma symptoms twice a week or more on average in the month prior to study entry
  2. Nocturnal awakening with asthma symptoms more than once per week on average in the month prior to study entry
  3. Two or more emergency department visits, unscheduled physician visits, prednisone courses, or hospitalizations for asthma in the 12 months prior to study entry
  4. Juniper Asthma Control Score (ACS) of 1.25 or greater at the first screening visit
* Absence of GERD symptoms at the time of study entry

Exclusion Criteria:

* Previous anti-reflux or peptic ulcer surgery
* Previous tracheoesophageal fistula repair
* FEV1 less than 60% of predicted normal value at screening visit and as measured immediately before methacholine bronchoprovocation; methacholine bronchoprovocation will be limited to participants with a FEV1 greater than or equal to 70% of predicted value in accordance with American Thoracic Society (ATS) guidelines
* History of a premature birth of less than 33 weeks gestation or any neonate requiring a significant level of respiratory care, including mechanical ventilation
* Any major chronic illness, including but not limited to non-skin cancer, cystic fibrosis, bronchiectasis, myelomeningocele, sickle cell anemia, endocrine disease, congenital heart disease, congestive heart failure, stroke, severe hypertension, insulin-dependent diabetes mellitus, kidney failure, liver disorder, immunodeficiency state, significant neuro-developmental delay or behavioral disorder (excluding mild attention deficit hyperactivity disorder), or other condition that would interfere with participation in the study
* History of phenylketonuria
* Medications for treatment of GI symptoms (e.g., proton pump inhibitors, H2 blockers, bethanechol, metoclopramide) in the month prior to study entry (intermittent anti-acids are allowed)
* Use of theophylline preparations, azoles, anti-coagulants, insulin for Type I diabetes, digitalis, or oral iron supplements when administered for iron deficiency in the month prior to study entry
* Use of any investigative drug in the 2 months prior to study entry
* Previous adverse effects from lansoprazole, other proton pump inhibitors, or sensitivity to aspartame
* Inability or unwillingness of the legal guardian to provide consent
* Inability or unwillingness of the child to provide assent
* Inability to take study medication
* Inability to perform baseline measurements
* Less than 80% completion of screening period diaries
* Inability to contact by telephone
* Planning to move out of the area in the 6 months following study entry
* Pregnancy
B: Inclusion Criteria:

* Physician-diagnosed asthma
* At least one of the following lung function criteria must be documented in the year prior to study entry:

  1. Bronchial hyperresponsiveness confirmed by 12% or greater improvement in amount of air expired in first second during a forced expiratory maneuver (FEV1) post-bronchodilator, or
  2. Methacholine post-diluent baseline (PC20) less than 16 mg/ml, or
  3. Exercise bronchoprovocation test with at least a 20% decrease in FEV1
* Currently on stable dose of daily inhaled corticosteroid for asthma control (i.e., inhaled corticosteroid equivalent to 2 puffs of 44 ug twice per day \[176 ug\] of fluticasone or greater for 8 weeks or longer prior to study entry)
* Poor asthma control as defined by any one of the following criteria:

  1. Use of beta-agonist for asthma symptoms twice a week or more on average in the month prior to study entry
  2. Nocturnal awakening with asthma symptoms more than once per week on average in the month prior to study entry
  3. Two or more emergency department visits, unscheduled physician visits, prednisone courses, or hospitalizations for asthma in the 12 months prior to study entry
  4. Juniper Asthma Control Score (ACS) of 1.25 or greater at the first screening visit
* Absence of GERD symptoms at the time of study entry

Exclusion Criteria:

* Previous anti-reflux or peptic ulcer surgery
* Previous tracheoesophageal fistula repair
* FEV1 less than 60% of predicted normal value at screening visit and as measured immediately before methacholine bronchoprovocation; methacholine bronchoprovocation will be limited to participants with a FEV1 greater than or equal to 70% of predicted value in accordance with American Thoracic Society (ATS) guidelines
* History of a premature birth of less than 33 weeks gestation or any neonate requiring a significant level of respiratory care, including mechanical ventilation
* Any major chronic illness, including but not limited to non-skin cancer, cystic fibrosis, bronchiectasis, myelomeningocele, sickle cell anemia, endocrine disease, congenital heart disease, congestive heart failure, stroke, severe hypertension, insulin-dependent diabetes mellitus, kidney failure, liver disorder, immunodeficiency state, significant neuro-developmental delay or behavioral disorder (excluding mild attention deficit hyperactivity disorder), or other condition that would interfere with participation in the study
* History of phenylketonuria
* Medications for treatment of GI symptoms (e.g., proton pump inhibitors, H2 blockers, bethanechol, metoclopramide) in the month prior to study entry (intermittent anti-acids are allowed)
* Use of theophylline preparations, azoles, anti-coagulants, insulin for Type I diabetes, digitalis, or oral iron supplements when administered for iron deficiency in the month prior to study entry
* Use of any investigative drug in the 2 months prior to study entry
* Previous adverse effects from lansoprazole, other proton pump inhibitors, or sensitivity to aspartame
* Inability or unwillingness of the legal guardian to provide consent
* Inability or unwillingness of the child to provide assent
* Inability to take study medication
* Inability to perform baseline measurements
* Less than 80% completion of screening period diaries
* Inability to contact by telephone
* Planning to move out of the area in the 6 months following study entry
* Pregnancy
C: Inclusion Criteria:

* Adults with diagnosis of asthma since at least 6 months.
* Symptoms of asthma during run-in.
* At least 3 months history and present symptoms of 1 or more of the following: burning feeling behind breastbone, pain behind breastbone, acid taste in the mouth.

Exclusion Criteria:

* Patients with clinically relevant abnormalities.
* Patients with a smoking history of ≥10 pack-year.
* Patients who have had previous surgery on the esophagus or the stomach.
D: Inclusion Criteria:

* The general goal of patient selection is to enroll patients for whom asthma physicians might prescribe GERD treatment, but where there is uncertainty whether it might be effective.
* Age 18 or older
* Physician diagnosed asthma
* If amount of air expired in the first second during a forced expiratory maneuver (FEV1) is greater than or equal to 70% predicted normal pre-bronchodilator: demonstrate methacholine 20% from post-diluent baseline (PC20). PC20 less than 16 mg/ml during Visit 1
* If FEV1 less than 70% and greater than or equal to 50% predicted normal pre-bronchodilator: demonstrate 12% reversibility during Visit 1 or within past 12 months
* Currently on stable dose of daily inhaled steroids for asthma control, i.e., inhaled corticosteroid equivalent to 400 ug/day of fluticasone44 or greater for 8 weeks or longer
* Poor asthma control: Either of the following; a score of 1.5 or greater on the Juniper Asthma Control Questionnaire; two or more episodes of asthma symptoms in the past 12 months with each episode requiring at least one of the following: an emergency department visit, unscheduled physician visit, prednisone course, hospitalization
* Non-smoker for 6 months or longer
* Less than 10 pack/year smoking history

Exclusion Criteria:

* Surgery: Previous anti-reflux or peptic ulcer surgery
* Pulmonary function: FEV1 less than 50% predicted normal pre-bronchodilator
* GERD Symptoms: Severe reflux constituting a clinical indication for treatment with a PPI or H2 blocker, typically two or more episodes per week of heartburn requiring antacids
* Other major chronic illnesses; conditions which in the judgment of the Study Physician would interfere with participation in the study, e.g., non-skin cancer, endocrine disease, coronary artery disease, congestive heart failure, stroke, severe hypertension, Type 1 insulin dependent diabetes mellitus, renal failure, liver disorders, immunodeficiency states, major neuropsychiatric disorder
* Medication use: Anti-reflux medication (proton pump inhibitors or H2 blockers) within 1 month Theophylline, azoles, iron, anti-coagulants, insulin (for Type I diabetes), digitalis, any investigative drugs within 1 month
* Drug allergy: Previous adverse effects from proton pump inhibitors or methacholine challenge
* Females of childbearing potential: Pregnant or lactating, unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal)
* Inability or unwillingness to provide consent
* Inability to perform baseline measurements
* Completion of less than 10 of the last 14 days of screening period diary entry
* Inability to be contacted by telephone
* Intention to move out of the area within 6 months

Answer: C