Safety, Tolerability, and Pharmacokinetic Study of Pregabalin in Pediatric Patients With Partial Onset Seizures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00437281
First received: February 16, 2007
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of pregabalin in pediatric patients with partial onset seizures that are incompletely controlled on their current medications.


Condition Intervention Phase
Epilepsies, Partial
Drug: Placebo
Drug: Pregabalin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled, Escalating Dose, Multiple Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Pregabalin In Pediatric Patients With Partial Onset Seizures

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Treatment-Emergent Adverse Events (AEs) by Severity: Double-blind Treatment [ Time Frame: Baseline to Day 7 ] [ Designated as safety issue: Yes ]
    Analysis for severity of AEs was performed separately for double-blind and open-label treatment. AE = any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AEs were classified as mild, moderate and severe based on severity assessment: Mild = no interference with participant's usual function; Moderate = some interference with participant's usual function; Severe = significant interference with participant's usual function. Treatment-emergent events for double-blind treatment included events between baseline and Day 7 that were absent before treatment or that worsened relative to pretreatment state. Participants may experience more than 1 AE.

  • Number of Treatment-Emergent Adverse Events (AEs) by Severity: Open-label Treatment [ Time Frame: Day 8 up to 28 days after open-label dose of study medication ] [ Designated as safety issue: Yes ]
    Analysis for severity of AEs was performed separately for double-blind and open-label treatment. AE = any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AEs were classified as mild, moderate and severe based on severity assessment: Mild = no interference with participant's usual function; Moderate = some interference with participant's usual function; Severe = significant interference with participant's usual function. Treatment-emergent events for open-label treatment included events between Day 8 and 28 days after the open-label dose that were absent before treatment or that worsened relative to pretreatment state. Participants may experience more than 1 AE.


Secondary Outcome Measures:
  • Number of Participants With Clinically Significant Change in Physical and Neurological Findings [ Time Frame: Baseline up to 7 days post-last dose of study medication ] [ Designated as safety issue: Yes ]
    Full physical examination included examination of the abdomen, breasts, lungs, lymph nodes, mouth, genitourinary, musculoskeletal and neurological systems, skin, extremities, head, heart, ears, eyes, neck, nose, ocular fundi, throat and thyroid gland. The neurological exam was performed by a pediatric neurologist or qualified investigator.

  • 28-Day Seizure Frequency Rate [ Time Frame: Baseline up to 7 days post-last dose of study medication ] [ Designated as safety issue: Yes ]
    Seizure frequency was reported by participant's parent or guardian from randomization to 7 days post-last dose of study medication. 28-day seizure frequency rate = (number of seizures in observation period/number of days in observation period)*28.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Multiple-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Area under the curve from time zero to the end of dosing interval (AUCtau), where dosing interval was 12 hours, for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). Results are normalized to individual participant's Day 8 dose.

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: Single-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). Results are normalized to individual participant's Day 8 dose.

  • Maximum Observed Plasma Concentration (Cmax): Multiple-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Cmax for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants). Results are normalized to individual participant's Day 8 dose.

  • Maximum Observed Plasma Concentration (Cmax): Single-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Cmax for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants). Results are normalized to individual participant's Day 8 dose.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax): Multiple-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Tmax for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants).

  • Time to Reach Maximum Observed Plasma Concentration (Tmax): Single-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Tmax for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants).

  • Plasma Decay Half-Life (t1/2): Multiple-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. t1/2 for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants).

  • Plasma Decay Half-Life (t1/2): Single-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. t1/2 for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants).

  • Apparent Oral Clearance (CL/F): Multiple-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants).

  • Apparent Oral Clearance (CL/F): Single-Dose Analysis [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants).

  • Renal Clearance (CLr): Multiple-Dose Analysis [ Time Frame: 0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time. CLr for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants).

  • Renal Clearance (CLr): Single-Dose Analysis [ Time Frame: 0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8 ] [ Designated as safety issue: No ]
    Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time. CLr for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning was to be reported (single-dose participants).


Enrollment: 65
Study Start Date: April 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo
Experimental: Pregabalin Drug: Pregabalin
Orally-administered pregabalin

  Eligibility

Ages Eligible for Study:   1 Month to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Partial onset seizures, incompletely controlled on 1-3 medications
  • At least 1 seizure per 28 days, on average

Exclusion Criteria:

  • Primary generalized seizures
  • Progressive CNS pathology
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00437281

Locations
United States, Alabama
Pfizer Investigational Site
Mobile, Alabama, United States, 36693
Pfizer Investigational Site
Mobile, Alabama, United States, 36604
United States, Arizona
Pfizer Investigational Site
Phoenix, Arizona, United States, 85016
United States, Arkansas
Pfizer Investigational Site
Jonesboro, Arkansas, United States, 72401
Pfizer Investigational Site
Little Rock, Arkansas, United States, 72205
United States, California
Pfizer Investigational Site
San Francisco, California, United States, 94143
United States, Florida
Pfizer Investigational Site
Gulf Breeze, Florida, United States, 32561
Pfizer Investigational Site
Pensacola, Florida, United States, 32504
Pfizer Investigational Site
Tampa, Florida, United States, 33603
Pfizer Investigational Site
Tampa, Florida, United States, 33609
United States, Missouri
Pfizer Investigational Site
Springfield, Missouri, United States, 65804
United States, New York
Pfizer Investigational Site
Buffalo, New York, United States, 14222
United States, North Carolina
Pfizer Investigational Site
Durham, North Carolina, United States, 27710
United States, Texas
Pfizer Investigational Site
Houston, Texas, United States, 77030
Pfizer Investigational Site
San Antonio, Texas, United States, 78258
Korea, Republic of
Pfizer Investigational Site
Seoul, Korea, Republic of, 120-752
Mexico
Pfizer Investigational Site
Mexico, DF, Mexico, 06720
Pfizer Investigational Site
Guadalajara, Jalisco, Mexico, 44280
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00437281     History of Changes
Other Study ID Numbers: A0081074
Study First Received: February 16, 2007
Results First Received: September 16, 2013
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Partial-onset seizures; epilepsy; pediatric; pregabalin; safety; tolerability; pharmacokinetics

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants

ClinicalTrials.gov processed this record on April 17, 2014