Primary Objective- To evaluate the feasibility and test-retest variability of nerve excitability threshold tracking - To investigate the sensitivity of nerve excitability measures to detect the effects of mexiletine- To investigate the sensitivity…
ID
Source
Brief title
Condition
- Other condition
- Peripheral neuropathies
Synonym
Health condition
Pain
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamic endpoints:
- Nerve excitability threshold endpoints
For further information please see protocol page 36 and 37.
Secondary outcome
- PainCart endpoints
- Intra-epidermal electrical stimulation endpoints
- Tolerability / safety endpoints
Exploratory endpoints
Pharmacokinetic analysis will only be performed if a relevant pharmacodynamic
effect is observed. Data will be used for PK or PK-PD modelling.
Background summary
Neuronal excitability is largely dependent on voltage-gated sodium and
potassium channels. In this study, we will investigate the effects of two drugs
that inhibit the sodium channels, namely mexiletine and lacosamide, on nerve
excitability and evoked pain tests in healthy subjects.
Measurement of peripheral nerve excitability would be an interesting biomarker
for the efficacy of current and new treatments that influence the nerves. In
this study we will validate nerve excitability threshold tracking, a
measurement technique for neuronal excitability. The placebo-controlled
mexiletine and lacosamide administration should inform us about the sensitivity
of threshold tracking to sodium channel blockade and will serve as a benchmark
for future studies with selective sodium channel blockers.
Additionally, the effect of sodium channel blockers on evoked pain tests,
namely the PainCart test battery and intra-epidermal electrical stimulation
(IES), will be investigated.
Study objective
Primary Objective
- To evaluate the feasibility and test-retest variability of nerve excitability
threshold tracking
- To investigate the sensitivity of nerve excitability measures to detect the
effects of mexiletine
- To investigate the sensitivity of nerve excitability measures to detect the
effects of lacosamide.
Study design
This is a randomized, double-blind, double-dummy, placebo-controlled, three-way
crossover study to investigate the effects of mexiletine and lacosamide on
nerve excitability and evoked pain tests in healthy subjects.
Intervention
* mexiletine (namuscla) 333 mg,
* oral administration of lacosamide 300 mg.
Study burden and risks
Mexiletine and lacosamide are registered drugs. The safety profiles of these
compounds are known. However, side effects might occur. Therefore, study drug
administrations will be done in the clinic under medical supervision. Subjects
will be closely monitored and will only be discharged from the unit if their
medical condition allows this. As subjects will receive single doses of the two
registered drugs, the risk is small and therefore acceptable compared to the
scientific benefit.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
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. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.
5. 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.
Exclusion criteria
1. Evidence of any active or chronic disease or condition that could interfere
with, or for which the treatment of which 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.
8. Participation in an investigational drug or device study within 3 months
prior to first dosing, or for more than 4 times a year
17. Any current, clinically significant, known medical condition in particular
any existing conditions that would affect sensitivity to cold (such as
atherosclerosis, Raynaud*s disease, urticaria, hypothyroidism) or pain (disease
that causes pain, hypesthesia, hyperalgesia, allodynia, paraesthesia,
neuropathy, etc.).
18. Subjects indicating pain tests intolerable at screening or achieving
tolerance at >80% of maximum input intensity for any pain test for cold,
pressure and electrical tests.
19. History or presence of post-inflammatory hyperpigmentation.
20. Dark skin (Fitzpatrick skin type IV, V or VI), widespread acne, freckles,
tattoos or scarring on the back.
22. History of trauma to the upper extremities or other orthopaedic conditions
that, in the opinion of the investigator, could affect the electrophysiological
measurements.
23. History of (or symptoms indicating presence of) carpal tunnel syndrome.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003154-24-NL |
| CCMO | NL67037.056.18 |