A randomised, double-blind, placebo controlled, single and multiple dose escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of NMD670 in male and female healthy subjects and patients with myasthenia gravis.
- Conditions
- Myasthenia Gravis1000381610029317
- Registration Number
- NL-OMON54930
- Lead Sponsor
- MD Pharma A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 79
Main inclusion criteria healthy volunteers (Part A and B)
1. Signed informed consent prior to any study-mandated procedure
2. Part A1: Healthy male subjects, 18 to 45 years of age, inclusive at
screening.
3. Part A2: Healthy female subjects of non-childbearing potential, 18-65 years
of age, inclusive at screening.
4. Part B: Healthy male subjects 18-65 years of age, inclusive at screening.
5. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and
with a minimum weight of 50 kg.
6. All males 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.
7. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.
Main inclusion criteria myasthenia gravis patients (Part C)
1. Signed informed consent prior to any study-mandated procedure
2. Male and female subjects 18 and above years of age, inclusive at screening.
3. Diagnosis of myasthenia gravis, MGFA class I, II, III or IVa, based on
characteristic muscle weakness and a positive AChR or muscle-specific tyrosine
kinase (MuSK) antibody test. Subjects with MGFA 0 using pyridostigmine
(mestinon) may be included, if muscle weakness is present when refraining from
pyridostigmine (as assessed by a medical doctor based on an interview of the
patient at screening).
4. Patients using steroids should be using a stable dose of steroids for at
least 1 month before dosing, and the dose of steroids should be expected to
remain stable for the duration of the study.
5. Body mass index (BMI) between 18 and 34 kg/m2, inclusive at screening, and
with a minimum weight of 50 kg.
6. All women of child bearing potential and all males 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.
7. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.
8. Must be able to cease the use of pyridostigmine as per study requirements,
if applicable.
Main exclusion criteMain exclusion criteria healthy volunteers (Part A and B)
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). 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. 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.
4. Positive test for drugs of abuse at screening or pre-dose. Retesting is
allowed at the discretion of the Investigator.
5. Alcohol will not be allowed from at least 24 hours before screening or
pre-dose.
6. Smoker of more than 10 cigarettes per day prior to screening or who use
tobacco products equivalent to more than 10 cigarettes per day and unable to
abstain from smoking whilst in the unit.
7. Any confirmed significant allergic reactions (urticaria or anaphylaxis)
against any drug, or multiple drug allergies (non-active hay fever is
acceptable).
8. Any known factor, condition, or disease that might interfere with treatment
compliance, study conduct or interpretation of the results such as drug or
alcohol dependence or psychiatric disease.
9. History of trauma to the lower extremities or other conditions (most
importantly neurological or muscle diseases) that, in the opinion of the
investigator, could affect the electrophysiological measurements.
10. Excessive exercise within 7 days before study drug administration.
11. Clinically significant abnormalities in coagulation.
Main exclusion criteria myasthenia gravis patients (Part C)
1. Evidence of any active or chronic disease or condition apart from myasthenia
gravis, 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)). 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).
5. Use of any medicati
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Tolerability / safety endpoints<br /><br>The following endpoints will be determined at time points indicated in the<br /><br>Schedule of Assessments.<br /><br>* Serious adverse events (SAEs) and adverse events (AEs) will be collected<br /><br>throughout the study at every study visit.<br /><br>* Concomitant medication<br /><br>* Clinical laboratory tests<br /><br>o Haematology<br /><br>o Chemistry<br /><br>o Urinalysis<br /><br>o Coagulation<br /><br><br /><br>* Vital signs<br /><br>o Pulse Rate (bpm)<br /><br>o Systolic blood pressure (mmHg)<br /><br>o Diastolic blood pressure (mmHg)<br /><br>o Respiratory rate<br /><br>* ECG<br /><br>o Heart Rate (HR) (bpm), PR, QRS, QT, QTcF<br /><br>* 24-hour Holter recording<br /><br>* Handgrip dynamometry<br /><br>o Grip release profile; timeprofile from 100% maximum voluntary contraction<br /><br>(MVC) to 5% of the 100%MVC<br /><br>o 100%MVC (Part C only)</p><br>
- Secondary Outcome Measures
Name Time Method