Pyridostigmine and Ondansetron for Myasthenia Gravis Patients

A Phase II, Study to Evaluate the Safety and Tolerability of Pyridostigmine When Given With Ondansetron to Subjects With Anti-AchR Positive Myasthenia Gravis

This study is testing if adding ondansetron to pyridostigmine can help people with myasthenia gravis feel better by reducing stomach problems caused by the medication.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: DAS-MG, Inc (industry)
• Locations: 1 site (Kansas City, Kansas)
• Trial ID: NCT04226170 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the effects of combining pyridostigmine with ondansetron in patients diagnosed with anti-AchR antibody positive myasthenia gravis. The study involves a 6-week treatment period where participants are randomized into two groups: one receiving pyridostigmine with a placebo and the other receiving pyridostigmine with ondansetron. The aim is to assess the efficacy of ondansetron in alleviating gastrointestinal adverse events associated with pyridostigmine. Participants will maintain a daily GI symptom diary to monitor their symptoms throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of anti-AchR antibody positive myasthenia gravis who have experienced gastrointestinal adverse events related to pyridostigmine.

Not a fit: Patients who do not have a history of gastrointestinal adverse events related to pyridostigmine may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve the management of gastrointestinal side effects in myasthenia gravis patients taking pyridostigmine.

How similar studies have performed: While there have been studies on pyridostigmine for myasthenia gravis, the combination with ondansetron specifically for GI adverse events is a novel approach.

Eligibility criteria

Inclusion criteria

1. 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:

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 (SSRIs).

Where this trial is running

Kansas City, Kansas

• University of Kansas Medical Center — Kansas City, Kansas, United States (RECRUITING)

Study contacts

• Study coordinator: Martine Francis, BA

Conditions: Myasthenia Gravis