Myasthenia Gravis
Conditions
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.
Interventions
DRUGDAS-001
ondansetron + pyridostigmine
Sponsors
DAS-MG, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The only unblinded study member will be the pharmacist
Intervention model description
randomized to ondansetron + pyridostigmine or placebo+ pyridostigmine in a 3:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with change in the gastrointestinal (GI) side effects | 6 weeks | difference in GI side effects as measured by the GSRS-self (Gastrointestinal System Rating Scale - self-administered) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with change in in physical examine | 6 weeks | physical examination changes General appearance,Head, eyes, ears, nose, and throat, Respiratory, Cardiovascular, Musculoskeletal, Abdomen, Neurologic, Extremities, Dermatologic, Lymphatic) |
| Number of participants with change in in clinical laboratory evaluations | 6 weeks | changes in clinical laboratory evaluations (Creatinine, Potassium(K+),Sodium (Na+) , Chloride (Cl-), Magnesium (Mg++), Calcium, Inorganic phosphate, Glucose, Urea,Bilirubin (Total) ,Bilirubin (direct), AST, ALT, GGT, Alkaline phosphatase, Total Protein, Albumin,Hematocrit Hemoglobin Platelet count Red blood cell (RBC) count WBC count WBC differential Mean cell volume (MCV) Mean cell hemoglobin (MCH) MCH concentration (MCHC) |
| Number of participants with change in the side effects | 6 weeks | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 . Incidence and nature of adverse events |
| Plasma concentrations of pyridostigmine | 6 weeks | Cmax |
| Plasma concentrations of ondansetron | 6 weeks | Cmax |
| Number of participants with change in Electrocardiography (ECG) | 6 weeks | ECG (standard digital 12-lead in singlicate) |
Countries
United States
Outcome results
None listed