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Trial record 23 of 40 for:    CARBAMAZEPINE AND Valproic Acid

A Trial of Generic Substitution of Antiepileptic Drugs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02429596
Recruitment Status : Unknown
Verified April 2015 by IRCCS National Neurological Institute "C. Mondino" Foundation.
Recruitment status was:  Recruiting
First Posted : April 29, 2015
Last Update Posted : April 29, 2015
Sponsor:
Information provided by (Responsible Party):
IRCCS National Neurological Institute "C. Mondino" Foundation

Brief 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.


Condition or disease Intervention/treatment Phase
Epilepsy Drug: Experimental Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: A Randomized Controlled Trial of Generic Substitution of Antiepileptic Drugs
Study Start Date : May 2012
Estimated Primary Completion Date : May 2015
Estimated Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: Experimental Treatment
AED(s) currently taken (CBZ, VPA, TPM, OXC, LEV, LTG) will be substituted, starting with the morning dose on day 2, with an equivalent formulation available in the market. Namely, a brand product will be switched to a generic, randomly chosen among those available in the market, while maintaining unaltered the dosing regimen and times of administration.Likewise, a generic product will be switched to the brand or another generic.
Drug: Experimental
Switch from brand to generic
Other Names:
  • Lamictal
  • Acido Valproico
  • Keppra
  • Topamax
  • Tegretol
  • Tolep

No Intervention: No Experimental Treatment
When the randomized allocation requires continuation on the same product (control), the AED product(s) currently taken will be continued unaltered, with the same dosing regimen and times of administration.



Primary Outcome Measures :
  1. Serum drug concentration (25% change in serum drug concentration) [ Time Frame: After six months ]
    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. When comparing differences in serum concentration between post-randomization and baseline, the mean of the two values (post-absorptive and trough) measured on each occasion will be used because this provides a more accurate estimate of relative bioavailability.


Secondary Outcome Measures :
  1. Serum drug concentration (15% change in mean serum drug concentration) [ Time Frame: After six months ]
    proportion of patients who post-randomization will show a greater than 15% change in mean serum drug concentration compared with baseline

  2. Serum drug concentration (50% change in mean serum drug concentration) [ Time Frame: After six months ]
    proportion of patients who post-randomization will show a greater than 50% change in mean serum drug concentration compared with baseline

  3. Serum drug concentration (5, 25% and 50% change in either post-absorptive or trough serum drug concentration) [ Time Frame: After six months ]
    proportion of patients who will show a greater than 15, 25% and 50% change in either post-absorptive or trough serum drug concentration compared with baseline

  4. Serum drug concentration (distribution in individual serum drug concentrations) [ Time Frame: After six months ]
    distribution in individual serum drug concentrations post-randomization compared with baseline

  5. Serum drug concentration (mean percent change (and %CV) in serum drug concentration) [ Time Frame: After six months ]
    mean percent change (and %CV) in serum drug concentration post-randomization compared with baseline

  6. adverse events [ Time Frame: After three years ]
    proportion of patients with adverse events

  7. adverse events [ Time Frame: After three years ]
    adverse event (AEP) scores

  8. first seizure after randomization [ Time Frame: After three years ]
    interval elapsed between randomization and the first seizure

  9. products (by type of AED, specific product utilized, and type of switch (brand to generic and generic to generic) [ Time Frame: After three years ]
    the above outcome measures, by type of AED, specific product utilized, and type of switch (brand to generic and generic to generic).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older;
  • currently being treated and at steady-state with any product (brand or generic) of carbamazepine, valproic acid, topiramate, oxcarbazepine, levetiracetam and/or lamotrigine administered in two or three divided daily doses, either alone or in combination with other drugs;
  • a diagnosis of epilepsy or any other condition justifying prescription of AED therapy;
  • being admitted to hospital (or being already in hospital) for observation/diagnostic evaluation or any other indication;
  • expected to remain on the currently prescribed drug treatment for at least 5 days (or 6 days for patients receiving lamotrigine or topiramate without enzyme inducers, or receiving lamotrigine combined with enzyme inducers plus valproate);
  • willingness to provide free, informed consent.

Exclusion Criteria:

  • a history of known or suspected poor compliance;

    • recent changes in drug treatment, including potentially interacting comedication, which may have prevented attainment of steady-state conditions of the AED(s) being tested;
  • known disorders of gastric motility;
  • pregnancy or lactation;
  • any condition which is expected to alter the pharmacokinetics of the study drug(s) over the subsequent 5/6 days;
  • inability to fully understand the nature and implications of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02429596


Contacts
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Contact: Cinzia Fattore, MD +39 0382 380818 cinzia.fattore@mondino.it
Contact: Emanuela Gerosa, MD +39 0382 380282 emanuela.gerosa@mondino.it

Locations
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Italy
Clinica Neurologica, Ospedali Riuniti Not yet recruiting
Ancona, Italy
Contact: Leandro Provinciali, MD       leandroprovinciali@gmail.com   
Clinica Neurologica Amaducci, Policlinico di Bari Not yet recruiting
Bari, Italy
Contact: Angela La Neve, MD       centroepilessia@neurol.uniba.it   
Principal Investigator: Angela La Neve, MD         
U.S.C. Neurologia, Ospedali Riuniti Active, not recruiting
Bergamo, Italy
Dipartimento di Scienze Neurologiche, Università degli Studi di Bologna Recruiting
Bologna, Italy
Contact: Agostino Baruzzi, MD       agostino.baruzzi@unibo.it   
Contact: Barbara Mostacci, MD       barbara.mostacci@unibo.it   
Principal Investigator: Agostino Baruzzi, MD         
Unità Operativa Complessa di Neurologia, Ospedale di Bellaria Recruiting
Bologna, Italy
Contact: Roberto Michelucci, MD       roberto.michelucci@ausl.bologna.it   
Contact: Lilia Volpi, MD       lilia.volpi@ausl.bologna.it   
Centro Regionale dell'Epilessia, Azienda Ospedaliera Spedali Civili Not yet recruiting
Brescia, Italy
Contact: Luisa Antonini, MD       luisa.antonini@spedalicivili.brescia.it   
Azienda Ospedaliera, Policlinico Universitario Mater Domini Completed
Catanzaro, Italy, 88100
Azienda Ospedaliera ospedali Riuniti Active, not recruiting
Foggia, Italy
Azienda Ospedaliera Universitaria Policlinico Gaetano Martino Not yet recruiting
Messina, Italy
Contact: Edoardo Spina, MD       espina@unime.it   
Principal Investigator: Edoardo Spina, MD         
Clinica Neurologica, Ospedale San Gerardo Not yet recruiting
Monza, Italy
Contact: Carlo Ferrarese, MD       carlo.ferrarese@unimib.it   
Contact: Simone Beretta, MD       simone.beretta@unimib.it   
Clinica Neurologica, Azienda Ospedaliero-Universitaria Maggiore della Carità Recruiting
Novara, Italy
Contact: Roberto Cantello, MD         
Contact: Claudia Varrasi, MD       claudia.varrasi@libero.it   
S.C. di Neurofisiopatologia, Centro di Riferimento Regionale Umbro per l'Epilessia Not yet recruiting
Perugia, Italy
Contact: Teresa Anna Cantisani, MD       cantisani@yahoo.com   
UO di Neurologia, Azienda Ospedaliero Universitaria Pisana Active, not recruiting
Pisa, Italy
Centro Regionale Epilessie, Reggio Calabria e Università della Magna Graecia Recruiting
Reggio Calabria, Italy
Contact: Umberto Aguglia, MD       u.aguglia@tin.it   
Contact: Sara Gasparini, MD         
Dipartimento di Scienze Neurologiche, III Clinica Neurologica, Università "La Sapienza" Not yet recruiting
Roma, Italy
Contact: Anna Teresa Giallonardo, MD       annateresa.giallonardo@uniroma1.it   
Unità Complessa di Neurologia, Ospedale SS. Giovanni e Paolo Not yet recruiting
Venezia, Italy
Contact: Francesco Paladin, MD         
Sponsors and Collaborators
IRCCS National Neurological Institute "C. Mondino" Foundation
Investigators
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Principal Investigator: Emilio Perucca, MD IRCCS National Neurological Institute "C. Mondino" Foundation

Publications:

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Responsible Party: IRCCS National Neurological Institute "C. Mondino" Foundation
ClinicalTrials.gov Identifier: NCT02429596     History of Changes
Other Study ID Numbers: FARM9A8J83
First Posted: April 29, 2015    Key Record Dates
Last Update Posted: April 29, 2015
Last Verified: April 2015
Keywords provided by IRCCS National Neurological Institute "C. Mondino" Foundation:
antiepileptic drugs
generic substitution
Additional relevant MeSH terms:
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Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants