A study to evaluate the sensitivity of muscle velocity recovery cycles to determine changes in muscle excitability, by evaluating pharmacological effects in healthy subjects, and by comparing healthy subjects with myasthenia gravis patients

Completed

• Conditions: Method development; 10028302

• Registration Number: NL-OMON49444
• Lead Sponsor: Centre for Human Drug Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 11 June 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 22

Inclusion Criteria

Part A
1. Signed informed consent prior to any study-mandated procedure
2. Healthy male subjects, 18 to 45 years of age, inclusive at screening.
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and
with a minimum weight of 50 kg.
4. All subjects must practice effective contraception during the study and be
willing and able to continue contraception for at least 90 days after their
last dose of study treatment.
5. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.

Part B
1. Signed informed consent prior to any study-mandated procedure
2. Male and female subjects, 18 to 69 years of age, inclusive at screening.
3. Diagnosis of generalized myasthenia gravis, MGFA class II, III or IVa, based
on characteristic muscle weakness and with a positive AChR antibody test.
4. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.
5. Must be able to cease the use of pyridostigmine as per study requirements,
if applicable.

Exclusion Criteria

1. Evidence of any active or chronic disease or condition that could interfere
with, or for which the treatment of might interfere with, the conduct of the
study, or that would pose an unacceptable risk to the subject in the opinion of
the investigator (following a detailed medical history, physical examination,
vital signs (systolic and diastolic blood pressure, pulse rate, body
temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the
normal range may be accepted, if judged by the Investigator to have no clinical
relevance.
2. Clinically significant abnormalities, as judged by the investigator, in
laboratory test results (including hepatic and renal panels, complete blood
count, chemistry panel and urinalysis). Subjects with pre-dose findings of
clinically significant changes in electrolytes should be excluded. In the case
of uncertain or questionable results, tests performed during screening may be
repeated before randomization to confirm eligibility or judged to be clinically
irrelevant for healthy subjects.
3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening.
4. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and
diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg at
screening.
5. Abnormal findings in the resting ECG at screening or baseline defined as:
a. QTcF> 450 or < 300 msec
b. Notable resting bradycardia (HR < 50 bpm) or tachycardia (HR > 100 bpm)
c. Personal or family history of congenital long QT syndrome or sudden death;
d. Evidence of atrial fibrillation, atrial flutter, complete branch block,
Wolf-Parkinson-White Syndrome, or cardiac pacemaker
e. Ventricular tachyarrhythmia
f. Atrial tachyarrhythmia, fibrillation or flutter
g. Complete heart block (i.e. third-degree atrioventricular block) or any heart
block susceptible to evolve to complete heart block (first-degree
atrioventricular block with markedly prolonged PR interval (* 240 ms) and/or
wide QRS complex (* 120 ms), second-degree atrioventricular block, bundle
branch block, bifascicular and trifascicular block),
h. Sinus node dysfunction (sinus rate < 50 bpm, sinus arrest of >3.5 sec)
6. Use of any medications (prescription or over-the-counter [OTC]), within 14
days of study drug administration, or less than 5 half-lives (whichever is
longer). Exceptions are paracetamol (up to 4 g/day) and ibuprofen (up to
1g/day). Other exceptions will only be made if the rationale is clearly
documented by the investigator.
7. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days
of study drug administration, or less than 5 half-lives (whichever is longer).
Exceptions will only be made if the rationale is clearly documented by the
investigator.
8. Participation in an investigational drug or device study within 3 months
prior to first dosing, or for more than 4 times a year.
9. History of abuse of addictive substances (alcohol, illegal substances) or
current use of more than 21 units alcohol per week, drug abuse, or regular user
of sedatives, hypnotics, tranquillizers, or any other addictive agent
10. Positive test for drugs of abuse at screening or pre-dose.
11. Alcohol will not be allowed from at least 24 hours before screening or

Study & Design

• Study Type: Interventional
• Study Design: Not specified