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Pyridostigmine Bromide

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The dose of pyridostigmine will be based on the patient's prior experience with pyridostigmine under the assumption that the patient already gained sufficient experience during their disease course to know which dose is effective for them as patients are advised by their treating neurologist to continually adjust their dose based on their symptoms and side effects.

Same as "Experimental", however capsules contain placebo.

Patients will receive amifampridine 2 dd 15 mg and amifampridine 2 dd 30 mg as add-on to the pre-study dose of pyridostigmine.

Participants will receive pyridostigmine 10 mg tablets.

Pyridostigmine

Participants will receive amifampridine (base) with modified release 15 mg or 30 mg tablets.

Amifampridine (base) with modified release

The placebo tablets will be identical apart from the active substance (pyridostigmine)

Placebo

The placebo tablets will be identical apart from the active substance (amifampridine base)

Martijn R. Tannemaat, MD, PhD

Jan J.G.M. Verschuuren, MD, PhD

A randomized, double-blind, placebo controlled, crossover intervention study evaluating the effect of pyridostigmine (part 1) and amifampridine (part 2) in Myasthenia Gravis (MG).

In the first part of the study, patients who are currently using pyridostigmine will be randomly allocated to one of two consecutive treatment periods in which patients either first receive placebo and then their usual dose of pyridostigmine, or vice versa. Each treatment period lasts 5 days with a 2-day wash-out period between each treatment period. Measurements will be performed at every last day of a treatment period (day 5 and day 12).

In the second part of the study the effect of two doses of amifampridine as add-on to pyridostigmine will be studied. Patients will be randomly assigned to either one of three treatment sequences; 1) amifampridine 30 mg - amifampridine 60 mg - placebo or 2) amifampridine 60 mg - placebo - amifampridine 30 mg or 3) placebo - amifampridine 30 mg - amifampridine 60 mg. Again, each treatment period consists of 5 days and will be separated by a 2-day wash-out period. Measurements will be performed at every last day of treatment (day 19, day 26 and day 33).

Patients will have the option to participate in a substudy to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of amifampridine in AChR positive MG patients.

Pyridostigmine and Amifampridine for Myasthenia Gravis

IMproving Symptomatic Treatment With Pyridostigmine and Amifampridine: a Randomized Double-blinded, Placebo Controlled Crossover Trial in Patients With Myasthenia Gravis (IMPACT-MG)

The iMCQ is adapted by omitting the modules on medication and travel. The recall period for the iMCQ is set to 12 months.

The recall period for the iPCQ is set to 3 months.

NMD Pharma A/S

Leiden University Medical Center

Principal Investigator

De-novo: Each capsule contains 60 mg. pyridostigmine. 1 capsule is administered twice within 4 hours.

Chronic: Each capsule contains 60 mg. pyridostigmine. Number of administered capsules per dosage depend on the patient's usual dosage. Study drug is administered twice within 4 hours.

Patients are examined/rated before 1st dose, 1 hour after 1st dose, 1 hour after 2nd dose (Visit 1). After cross-over (Visit 2), patients will be rated open-label at 1 month (Visit 3) and 3 months (Visit 4).

Same as "Active", however capsules contain placebo.

Placebo oral capsule

Jan LS Thomsen, MD

Henning Andersen, MD PhD DMSc

A randomized, placebo-controlled, double-blinded cross-over study evaluating and quantifying the effect of pyridostigmine on muscle strength and symptoms in Myasthenia Gravis (MG)

The study aims to evaluate and quantify the effect of pyridostigmine on symptoms and muscle strength in newly-diagnosed patients and patients on stable medication.

Pyridostigmine treatment is initiated in the vast majority of MG patients. No studies have quantified the effect in a randomized trial, and no studies have examined the potential difference in effect in newly diagnosed patients as compared to patients on stable, antimyasthenic medications.

The study will investigate the effect in two groups

1. Newly diagnosed, treatment-naive patients.
2. MG patients on stable antimyasthenic medication.

Effect of Pyridostigmine (Mestinon) on Muscle Strength in Myasthenia Gravis

Quantitative Myasthenia Gravis (QMG) scale rate disease severity of myasthenia gravis on 13 items with a total score ranging from 0-39 (higher values representing more severe disease). Total score (0-39), ocular subitems (0-6), bulbar subitems (0-9), extremity/axial subitems (0-21) and respiratory subitem (0-3) will be reported.

Peak muscle torque expressed in newton meters based on 3 repeated maximal isometric contractions. Performed on shoulder abduction and knee extension.

Decrement in peak muscle torque expressed in newton meters per contraction during up to 50 repetitive maximal isokinetic contractions. Performed on shoulder abduction and knee extension.

The Myasthenia Gravis Composite (MG composite) scale rate disease severity of myasthenia gravis on 10 items with a score ranging from 0-50 (higher values representing more severe disease).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pyridostigmine and Amifampridine for Myasthenia Gravis	NCT05919407	Myasthenia Grav...	Pyridostigmine Amifampridine (... Placebo Placebo	18 Years -	Leiden University Medical Center
Effect of Pyridostigmine (Mestinon) on Muscle Strength in Myasthenia Gravis	NCT03510546	Myasthenia Grav...	Pyridostigmine Placebo oral ca...	18 Years - 90 Years	University of Aarhus

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