Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis
Purpose
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.
Condition
- Myasthenia Gravis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male and female subjects aged 18 years old and up who have been diagnosed with anti-AchR antibody positive myasthenia gravis. 2. Subjects can be either: currently taking pyridostigmine and after Lead-in Period experience dose limiting GI AEs related to pyridostigmine (must include nausea, vomiting or diarrhea) during Lead-in 3. Subjects must be willing and able to complete a GI symptom diary within a consistent timeframe on a daily basis. 4. Must be clinically stable in judgement of treating neurologists for past 3 months. 5. Must be positive for acetylcholine receptor antibodies. 6. Subjects must be able to swallow liquid. 7. Subjects must be in otherwise 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. 8. 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
- 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 (SSRIs).
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- randomized to ondansetron + pyridostigmine or placebo+ pyridostigmine in a 3:1 ratio.
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- The only unblinded study member will be the pharmacist
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator treatment |
ondansetron + pyridostigmine |
|
|
Placebo Comparator Placebo |
placebo+ pyridostigmine |
|
Recruiting Locations
University of Kansas Medical Center
Kansas City, Kansas 66160
Kansas City, Kansas 66160
More Details
- Status
- Recruiting
- Sponsor
- DAS-MG, Inc
Detailed Description
Methodology: This is a phase II, 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 with 2 groups. - Group A: Patients currently taking pyridostigmine and experiencing pyridostigmine-related gastrointestinal (GI) adverse events (AEs) within the past 14 days. - Group B: Patients not currently taking pyridostigmine due to a documented history of GI AEs. 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.