Clinical trial NCT04226170: Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis
Official title: A Phase II, Study to Evaluate the Safety and Tolerability of Pyridostigmine When Given With Ondansetron to Subjects With Anti-AchR Positive Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myasthenia Gravis
Lead sponsor: DAS-MG, Inc
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: randomized to ondansetron + pyridostigmine or placebo+ pyridostigmine in a 3:1 ratio.
Primary purpose: TREATMENT

Brief summary: 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.

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.

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).

Primary outcomes:
measure: Number of participants with change in the gastrointestinal (GI) side effects
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of participants with change in the side effects
timeFrame: 6 weeks
measure: Number of participants with change in in physical examine
timeFrame: 6 weeks
measure: Number of participants with change in in clinical laboratory evaluations
timeFrame: 6 weeks
measure: Number of participants with change in Electrocardiography (ECG)
timeFrame: 6 weeks
measure: Plasma concentrations of pyridostigmine
timeFrame: 6 weeks
measure: Plasma concentrations of ondansetron
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
References: