A safety and efficacy study of pregabalin in children 4-16 years of age for partial onset seizures

• Register: EUCTR
• Last refreshed on: 22 August 2016
• Main ID: EUCTR2010-020852-79-NL
• Date of registration: 29/06/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.235 East 42nd Street, New York, NY 10017
• Public title: A safety and efficacy study of pregabalin in children 4-16 years of age for partial onset seizures
• Scientific title: A DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER STUDY OF THE EFFICACY AND SAFETY OF PREGABALIN AS ADJUNCTIVE THERAPY IN CHILDREN 4 -16 YEARS OF AGE WITH PARTIAL ONSET SEIZURES
• Date of first enrolment: 28/07/2011
• Target sample size: 153
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020852-79
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Croatia, Czech Republic, Estonia, Finland, France, Greece, Guatemala, Hungary, India, Italy, Korea, Republic of, Lithuania, Malaysia, Netherlands, Panama, Philippines, Poland, Romania, Singapore, Sweden, Turkey

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that
the subject and/or parent/legally acceptable representative has been informed of all
pertinent aspects of the study. When there are two parents or two legally acceptable
representatives, consent should be obtained from both of the child’s parents/legal
representatives if present at the meeting where the informed consent document is signed. Subject to local regulations whenever the minor is able to give assent, the minor’s assent must also be obtained.
2. Subjects and/or parent(s)/legally acceptable representative who are willing and able to
comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Subjects and/or parent(s)/legally acceptable representative must be considered willing
and able to complete daily seizure diaries and monitor seizure frequency.
4. Male and female epilepsy subjects, 4 to 16 years of age inclusive on the date of the
Screening Visit.
5. Diagnosis of epilepsy with partial onset seizures classified as simple partial, complex
partial or partial becoming secondarily generalized, according to the International
League Against Epilepsy (ILAE)3 Diagnosis must be established by:
- Subject’s history (eg, description of seizures excluding confounding disorders such as pseudoseizures, syncopes etc) family history and neurological exam.
- Subjects must have had a contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and EEG testing within 24 months of the Screening Visit. Results must be consistent with the
diagnosis of focal-onset epilepsy and must demonstrate that no abnormality is
likely to be progressive.
- Confirmation of diagnosis by independent reviewer before randomization.
6. Must have a partial onset seizure frequency of at least 3 seizures per 28-day period
prior to screening. Must have a partial onset seizure frequency of =6 seizures and no
continuous 4 week seizure free period during the 8 week baseline phase prior to
randomization.
7. Currently receiving a stable dose of 1 to 3 antiepileptic drugs (stable within 28 days
prior to screening). Benzodiazepine medication used on a regular basis at a stable
dosage will be considered 1 of the concurrent antiepileptic treatments. A previously
implanted Vagus nerve stimulator (VNS) for the treatment of epilepsy is allowed and
will be considered one of the 3 antiepileptic treatments.
8. A 12-lead ECG at screening without significant abnormal findings as determined by
the investigator and confirmed by the Central ECG Reader.
Are the trial subjects under 18? yes
Number of subjects for this age range: 153
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Primary generalized seizures (including in the setting of co-existing partial onset
seizures) which include for example:
- Clonic, tonic and clonic-tonic seizures (note that partial onset seizures that become secondarily generalized are not exclusionary).
- Absence seizures.
- Infantile spasms.
- Myoclonic, myoclonic atonic, myoclonic tonic seizures.
2. Lennox-Gastaut syndrome, Benign Epilepsy with Centrotemporal Spikes (BECTS) and Dravet syndrome. 3. A current diagnosis of febrile seizures, or seizures related to an ongoing acute
medical illness. Any febrile seizures within 1 year of screening. 4. Status epilepticus within 1 year prior to screening. 5. Seizures related to drugs, alcohol, or acute medical illness. 6. Any change in AED regimen (type of medication or dose) within 28 days of the Screening Visit or during the Baseline Phase. 7. Progressive structural CNS lesion or a progressive encephalopathy.
8. Progressive errors of metabolism. 9. Known or suspected chronic hematologic, hepatic or renal disease (AST and ALT above 3 times the upper limit of normal (ULN); or bilirubin, BUN, or creatinine above 2 times the ULN within the previous 6 months prior to screening). 10. Estimated creatinine clearance (ClCR) <80 mL/min/1.73 m2. 11. Other severe acute or chronic medical or psychiatric condition (eg, current major depressive disorder;schizophrenia or other psychoses) or laboratory abnormality that may increase the risk associated with study participation or study medication administration or may interfere with the interpretation of the study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 12. Pregnant or nursing females (females who are menarchal must have a negative pregnancy test); menarchal females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least 14 days prior to the first dose of study medication until completion of the study.
13. Taking any non-antiepileptic (non-AED) medication that could alter the effectiveness
of the subject’s medication, response, seizure frequency or characteristics. Medications for Attention Deficit/Hyperactivity Disorder will be permitted if medication doses are stable and remain so throughout the duration of study. A
ketogenic diet will also be allowed given that the diet is adhered to for the duration of
the study. 14. The concomitant use of gabapentin is prohibited. 15. Use of cocaine, phencyclidine (PCP), or other illegal or illicit drugs is prohibited. Use of amphetamines, barbiturates, opiates, or benzodiazepines without a valid current prescription is prohibited.
16. History of lack of efficacy for treatment of epilepsy with pregabalin at presumed efficacious doses. 17. Known allergy or intolerance to pregabalin or other a2d ligands (eg, gabapentin).
18. Prior participation in a pregabalin clinical trial.
19. Treatment with pregabalin for any reason within 60 days prior to screening. 20. History of sensitivity to heparin or heparin induced thrombocytopenia. 21. Unwilling or unable to comply with the Life Style Guidelines. 22. Not reasonably expected to complete the trial.
23. Participation in other clinical studies within 30 days before the current study begins
and/or during study participation. 24. Subjects whose parents/legally acceptable representatives are investigational site staff
members or subjects whose parents/legally acceptable representa

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Partial onset seizures
MedDRA version: 16.1 Level: LLT Classification code 10034089 Term: Partial seizures NOS System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Lyrica
Pharmaceutical Form: Oral solution
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Other descriptive name: PREGABALIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Lyrica®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Concentration unit: mg milligram(s)
Concent

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the efficacy of two dose levels of
pregabalin (Level 1: 2.5 mg/kg/day; maximum 150 mg day and Level 2: 10 mg/kg/day; maximum 600 mg day) compared to placebo as an adjunctive treatment in reducing the frequency of partial onset seizures in pediatric subjects 4 to 16 years of age.

Primary end point(s): The primary endpoint will be the log-transformed (loge) 28-day seizure rate for all partial onset seizures collected during the 12 week double-blind treatment phase. Results will be reported as “percent reduction in seizures” relative to placebo. For calculation see protocol.

Secondary Objective: -To characterize the efficacy of pregabalin vs. placebo on the frequency of partial onset seizures as determined by responder rate in pediatric subjects 4 to 16 years of age.
-To assess the safety and tolerability of pregabalin in pediatric subjects 4 to 16 years
of age with partial onset seizures.

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Secondary end point(s): Responder Rate, defined as subjects who have a =50% reduction in partial seizure
rate from baseline during the double-blind treatment phase. Subjects meeting this
criterion will be considered a favorable outcome.

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary ID(s)

2010-020852-79-CZ

A0081041

Source(s) of Monetary Support

Pfizer Inc