The aim of this study is to investigate the pharmacokinetics of the extended release formulation of amifampridine. Secondary objective of the study is to develop a PKPD model of amifampridine in LEMS.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic parameters: Tmax, Cmax, AUC, VD, Ctrough,SS.
Secondary outcome
Pharmacodynamic endpoints: 3TUG scores, subject global impression (SGI) and
CMAP amplitude. The occurrence of side effects will also be assessed.
Background summary
Lambert-Eaton myasthenic syndrome (LEMS) is a very rare antibody-mediated
autoimmune disease of the neuromuscular junction. LEMS is characterized by
muscle fatigability with weakness in the limb girdle region as most important
complaint. Therapy can be divided in symptomatic treatment and
immunosuppressive treatment. Symptomatic treatment with amifampridine is the
only therapy currently authorized for use in LEMS patients. In the Netherlands
the first choice drug is amifampridine base in an extended release formulation,
instead of the currently authorized amifampridine phosphate in an immediate
release formulation. Although amifampridine base has not received formal
authorisation, its use is condoned by regulating authorities based on the
extensive (>40 year) experience with this drug, its lower costs and possibly
better safety profile due to its extended release properties. However, the
extended release properties of the formulation have been shown solely in in
vitro dissolution experiments, no in vivo pharmacokinetic parameters have been
collected.
Study objective
The aim of this study is to investigate the pharmacokinetics of the extended
release formulation of amifampridine. Secondary objective of the study is to
develop a PKPD model of amifampridine in LEMS.
Study design
A multiple dose open label study.
Study burden and risks
There is extensive experience with the use of amifampridine in patients with
LEMS and the dose used in this study is based on the patients clinical response
and side effects. Therefore the risk of serious (unexpected) side effects is
minimal.
There is no medicinal product started in this study. The intervention entails
extra measurements. Additional blood is collected and some pharmacodynamic
endpoints are measured more frequent than in common clinical practice, the risk
of these additional measurements is minimal. Additional risk may be the delay
of the first daily dose of amifampridine because patients will travel to the
research center withholding their first daily dose. The risk might be a minimal
increase in symptoms of LEMS. A long travel time will increase this risk and an
overnight stay near the research center will be offered to reduce this risk.
Benefits are more insight in the pharmacokinetics of amifampridine modified
release and with this insight more optimal dosing regimes can be prescribed.
Albinusdreef 2
Leiden 2300RC
NL
Albinusdreef 2
Leiden 2300RC
NL
Listed location countries
Age
Inclusion criteria
1. Age >18 years
2. Clinical diagnosis of LEMS
3. Presence of Voltage Gated Calcium Channel Antibodies (VGCC antibodies)
4. Current use of amifampridine modified release
5. Receiving a stable dose of amifampridine modified release
Exclusion criteria
1. The patient is unable to fill out the study questionnaires or be interviewed
in Dutch or English, or is unable to undergo the tests needed for the study, or
is unable to give informed consent for participation in the study.
2. The investigator can exclude patients for this trial which are deemed not
suitable for any reason.
Design
Recruitment
metc-ldd@lumc.nl
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 |
|---|---|
| CCMO | NL85775.058.24 |