Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis
Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis
This is a phase II, single center, randomized, double-blind, placebo-controlled, study in
 patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.
Methodology: This is a phase II, single center, randomized, double-blind, placebo-controlled,
 study in patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.

 Study Design: The clinical trial will be conducted over a 6-week treatment period.

 -  Group A: Patients currently taking pyridostigmine and experiencing
 pyridostigmine-related gastrointestinal (GI) adverse events (AEs) within the past 7 days

 -  Group B: Patients not currently taking pyridostigmine due to GI AEs or that had their
 dose reduced due to pyridostigmine related GI AEs Group A will be enrolled in the study
 and randomized to either the control (pyridostigmine+ placebo) or the test group
 (pyridostigmine + ondansetron) and treated for 6 weeks. Following enrolment, patients
 may (if needed) titrate up their pyridostigmine dose at the investigator's discretion
 each week to the highest dose deemed appropriate, tolerable and safe by the
 Investigator.

 Group B patients not currently taking pyridostigmine due to GI AEs will initiate
 pyridostigmine at a dose determined by the investigator based on the patient's history and
 may titrate as deemed tolerable and safe by Investigator during screening; patients on a
 reduced dose due to pyridostigmine related GI AEs may titrate pyridostigmine as deemed
 tolerable and safe by the investigator during screening. If patients in Group B experience GI
 AEs that fulfil enrolment criteria, along with all other inclusion/exclusion criteria, they
 will be enrolled into the study at that dose and randomized to either the control
 (pyridostigmine+ placebo) or the test group (pyridostigmine + ondansetron) and treated for 6
 weeks. Following enrolment, patients may (if needed) titrate up their pyridostigmine dose at
 the investigator's discretion each week to the highest dose deemed appropriate, tolerable and
 safe by the Investigator.
Inclusion Criteria:

 1. diagnosed with myasthenia gravis and who are currently taking pyridostigmine and
 experienced pyridostigmine-related GI side effects within the past 7 days.

 2. GSRS rating of at least Moderate discomfort on questions 5, 11, and 12.

 3. Subjects must be willing and able to complete a GI symptom diary within a consistent
 timeframe on a daily basis.

 4. Subjects must be able to tolerate a pyridostigmine dose of 30mg TID.

 5. Must be clinically stable in judgement of treating neurologists for past 3 months.

 6. Must have AchR antibody positive MG.

 7. Subjects must be able to swallow liquids.

 8. Subjects must be in good health as determined by their medical history, physical
 examination, vital signs, and laboratory tests. A subject with a medical abnormality
 may be included only if the investigator or designee considers that the abnormality
 will not introduce significant additional risk to the subject's health or interfere
 with study objectives.

 9. Subjects must have signed an informed consent form indicating that they understand the
 purpose of and procedures required for the study and are willing to participate in the
 study and comply with the study procedures and restrictions.

 Exclusion Criteria:

 Key exclusion criteria:

 The criteria for exclusion of a subject from enrollment in the study are as follows:

 1. Any acute or chronic diseases which are associated with GI distress (such as nausea,
 vomiting, or diarrhea), which could interfere with the subjects' safety during the
 trial, expose them to undue risk, or interfere with the study objectives.

 2. History or presence of hepatic, or renal disease or other condition known to interfere
 with the absorption, distribution, metabolism, or excretion of drugs.

 3. History of substance abuse, known drug addiction, or positive test for drugs of abuse
 or alcohol.

 4. Patients currently using marijuana for any reason (medical or recreational).

 5. Known hypersensitivity to pyridostigmine, or to ondansetron or similar 5-HT3 serotonin
 receptor antagonists.

 6. ECG changes including QT interval prolongation and congenital long QT syndrome.
 Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart
 failure, bradyarrhythmia's or other medicinal products that lead to QT prolongation.

 7. Treatment with drugs affecting peripheral cholinergic transmission within 1 month of
 study entry (with the exception of pyridostigmine).

 8. Subjects unlikely to co-operate during the study, and/or be questionably compliant in
 the opinion of the investigator.

 9. Patients currently being treated with narcotics.

 10. Patients being treated with aminoglycoside antibiotics, which are contraindicated in
 myasthenia gravis.

 11. Patients unable to be contacted in case of an emergency.

 12. Intake of an investigational drug within 30 days of study entry.

 13. Pregnancy and women of childbearing potential not willing to follow the birth control
 requirements as described in the informed consent or breastfeeding.

 14. History or presence of obstructive pulmonary disease or urinary obstruction
 (contraindication for pyridostigmine).

 15. This use of selective serotonin reuptake inhibitors (SSRI's).