A Trial of Generic Substitution of Antiepileptic Drugs
Status:
Unknown status
Trial end date:
2015-05-01
Target enrollment:
Participant gender:
Summary
Background. Anecdotal reports and uncontrolled studies have described an association between
generic substitution of antiepileptic drugs (AEDs) and adverse events, including loss of
seizure control. Although these results are likely to be influenced by methodological bias,
they have led to a strong opposition, among physicians and patients, to the use of generic
products in epilepsy.
Objectives. The primary objective is to assess potential risks associated with substitution
of the currently taken AED product with an equivalent product, using as endpoint changes in
serum drug levels at steady-state after substitution compared with baseline. Secondary
objectives will be the assessment of inter-subject variability in serum drug concentration on
an unchanged treatment schedule, and evaluation of potential short-term changes in seizure
control and adverse events rate.
Methods. The study will use an experimental randomized open-label non-inferiority design. The
population will consist of 200 adults stabilized on chronic treatment with carbamazepine,
valproic acid, topiramate, oxcarbazepine, levetiracetam or lamotrigine and admitted to
hospital for diagnostic evaluation or other indications, with no expected treatment changes
during the subsequent 5 to 6 days. Patients will be randomized to two groups. One group will
continue to receive the AED products used before enrollment (brand or generic), whereas the
other group will be switched to an alternative equivalent product. Dosing schedules of the
AEDs being tested as well as comedications will be unaltered throughout the 6- to 7day period
of the study. Serum AED levels (mean of two values obtained at peak and trough, respectively
in the evening and the next morning) will be measured on day 1 (baseline) and 5 days
post-randomization (6 days for patients receiving AEDs with half-lives above 12 h). The
primary outcome endpoint will be the proportion of patients who, post-randomization, show a
greater than 25% change in serum drug concentration compared with baseline. Secondary
endpoints will include comparison of distributions of rough serum concentration changes
between groups, other pharmacokinetic parameters, time to first seizure, total number of
seizures, and adverse events.
Phase:
Phase 4
Details
Lead Sponsor:
IRCCS National Neurological Institute "C. Mondino" Foundation