Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1/2 Double-Blind Study of the Safety and Efficacy of Albuterol on Motor Function in Individuals With Late-onset Pompe Disease Receiving Enzyme Replacement Therapy
Brief Summary: In this study the study team proposes to investigate the efficacy of albuterol on motor function of individuals with Late Onset Pompe Disease (LOPD) who are receiving enzyme replacement therapy, given albuterol was well-tolerated in patients with Late Onset Pompe Disease.


Options:
A: Inclusion Criteria:

* Patient must have completed protocol AGLU02704 (NCT00158600)
* Patient must provide signed, informed consent prior to performing any study-related procedures
* Patient (and patient's legal guardian if patient is under 18 years of age) must have the ability to comply with the clinical protocol
* A female patient of childbearing potential must have a negative pregnancy test at Baseline. (note: all female patients of childbearing potential and sexually mature males must use a medically accepted method of contraception throughout the study.)

Exclusion Criteria:

* The patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, would preclude treatment with alglucosidase alfa.
B: Inclusion Criteria:

1. Subject must provide signed informed consent prior to any study-related procedures being performed.
2. Male and female subjects are ≥ 18 years old and weigh ≥ 40 kg at screening.
3. Female subjects of childbearing potential and male subjects must agree to use medically accepted methods of contraception during the study and for 90 days after the last dose of study drug.
4. Subject must have a diagnosis of LOPD based on documentation of one of the following:

   1. deficiency of GAA enzyme
   2. GAA genotyping
5. Subject is classified as one of the following with respect to ERT status:

   1. ERT-experienced, defined as currently receiving standard of care ERT (alglucosidase alfa) at the recommended dose and regimen (ie, 20 mg/kg dose every 2 weeks) for ≥ 24 months
   2. ERT-naïve, defined as never having received investigational or commercially available ERT
6. Subject has a sitting FVC ≥ 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening.
7. Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:

   1. both screening values of 6MWD are ≥ 75 meters
   2. both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults
   3. the lower value of 6MWD is within 20% of the higher value of 6MWD

Exclusion Criteria

1. Subject has received any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before Day 1 or is anticipated to do so during the study.
2. Subject has received gene therapy for Pompe disease
3. Subject is taking any of the following prohibited medications within 30 days before Day 1:

   * miglitol (eg, Glyset)
   * miglustat (eg, Zavesca)
   * acarbose (eg, Precose or Glucobay)
   * voglibose (eg, Volix, Vocarb, or Volibo)

   Note: None of these medications have a half-life that, when multiplied by 5, is longer than 30 days.
4. Subject requires the use of invasive or noninvasive ventilation support for \> 6 hours per day while awake.
5. Subject has a hypersensitivity to any of the excipients in ATB200, alglucosidase alfa, or AT2221.
6. Subject has a medical condition or any other extenuating circumstance that may, in the opinion of the investigator or medical monitor, pose an undue safety risk to the subject or may compromise his/her ability to comply with or adversely impact protocol requirements. This includes clinical depression (as diagnosed by a psychiatrist or other mental health professional) with uncontrolled or poorly controlled symptoms.
7. Subject, if female, is pregnant or breastfeeding at screening.
8. Subject, whether male or female, is planning to conceive a child during the study.
9. Subject does not have documentation of diagnosis of Pompe disease and refuses to undergo genetic testing.
C: Inclusion Criteria:

* Patient must provide signed, informed consent prior to performing any study-related procedures.
* Patient must have a diagnosis of Pompe disease based on deficient endogenous GAA activity in cultured skin fibroblasts of less than or equal to 40% of the normal mean of the testing laboratory and 2 confirmed GAA gene mutations;
* Patient must be greater than or equal to 8 years of age at the time of enrollment;
* Patient must be able to ambulate 40 meters (approximately 130 feet) in 6 minutes on each test performed on two consecutive days (use of assistive devices such as a walker, cane, or crutches, is permitted);
* Patient must have an FVC of greater than or equal to 30% and \< 80% predicted in the upright position;
* Patient must have a postural drop in FVC (liters) of at least 10% from the upright to the supine position;
* Patient must have proximal muscle weakness in the lower limbs based on unilateral QMT of the knee extensors defined as \< 80% of the predicted value based on age, gender and body size
* Patient must be able to tolerate pulmonary function testing (PFT) and muscle testing in the supine position;
* Patient must have testable muscle in bilateral knee flexors and knee extensors, and testable muscle in bilateral elbow flexors and elbow extensors;
* Patient must be able to provide reproducible muscle and pulmonary function test results;
* Patient (and patient's legal guardian if patient is \< 18 years of age) must have the ability to comply with the clinical protocol;
* A female patient of childbearing potential must have a negative pregnancy test (urine) at Baseline. Note: All female patients of childbearing potential and sexually mature males must use a medically accepted method of contraception throughout the study.

Exclusion Criteria:

* Patient requires the use of invasive ventilatory support;
* Patient requires the use of noninvasive ventilatory support while awake and in an upright position;
* Patient has received enzyme replacement therapy with GAA from any source;
* Patient has used an investigational product within 30 days prior to study enrollment, or is currently enrolled in another study which involves clinical evaluations, unless prior approval is given by Genzyme;
* Patient has a major congenital anomaly, medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities;
D: Inclusion Criteria:

1. Diagnosis of Pompe disease by blood acid alpha-glucosidase assay and acid alpha-glucosidase gene sequencing,
2. Age: 18+ years at enrollment.
3. Receiving enzyme replacement therapy at standard dose (20 mg/kg every 2 weeks) for at least 52 weeks.
4. Subjects are capable of giving written consent.

Exclusion Criteria:

1. Continuous invasive ventilation (via tracheostomy or endotracheal tube).
2. Clinically relevant illness within two weeks of enrollment including fever \> 38.2 C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy.
3. Chronic heart disease (Myocardial infarction in the past 2 months, arrhythmia, cardiomyopathy).
4. History of seizure disorder.
5. History of diabetes.
6. Hypokalemia.
7. History of hyperthyroidism.
8. Pregnancy.
9. Patients on a non-standard schedule for enzyme replacement therapy; for example, weekly infusions as opposed to infusions every two weeks.
10. Anti-rhGAA antibody titer \> 1:100,000
11. History of hypersensitivity to Beta 2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent)..
12. The use of the following medications:

    * diuretics (water pill);
    * digoxin (digitalis, Lanoxin);
    * beta-blockers such as atenolol (Tenormin), metoprolol (Lopressor), and propranolol (Inderal);
    * tricyclic antidepressants such as amitriptyline (Elavil, Etrafon), doxepin (Sinequan), imipramine (Janimine, Tofranil), and nortriptyline (Pamelor);
    * Monoamine oxidase inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate); or
    * bronchodilators such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Brethine, Bricanyl), salmeterol (Serevent), isoetharine (Bronkometer), metaproterenol (Alupent, Metaprel), or isoproterenol (Isuprel Mistometer) within 12 weeks prior to enrollment.

Answer: D