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

A Placebo-Controlled, Escalating Dose, Multiple Dose Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Pregabalin In Pediatric Patients With Partial Onset Seizures

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.

Study Overview

• Status: Completed
• Conditions: Epilepsies, Partial
• Intervention / Treatment: Drug: Placebo; Drug: Pregabalin

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
• Mexico
  • DF
    • Mexico, DF, Mexico, 06720
      • Pfizer Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Pfizer Investigational Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Pfizer Investigational Site
    • Mobile, Alabama, United States, 36693
      • Pfizer Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Pfizer Investigational Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Pfizer Investigational Site
    • Little Rock, Arkansas, United States, 72205
      • Pfizer Investigational Site
  • California
    • San Francisco, California, United States, 94143
      • Pfizer Investigational Site
  • Florida
    • 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
      • Pfizer Investigational Site
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Pfizer Investigational Site
  • New York
    • Buffalo, New York, United States, 14222
      • Pfizer Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Pfizer Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78258
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Pregabalin	Drug: Pregabalin; Orally-administered pregabalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment-Emergent Adverse Events (AEs) by Severity: Double-blind Treatment	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.	Baseline to Day 7
Number of Treatment-Emergent Adverse Events (AEs) by Severity: Open-label Treatment	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.	Day 8 up to 28 days after open-label dose of study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Change in Physical and Neurological Findings	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.	Baseline up to 7 days post-last dose of study medication
28-Day Seizure Frequency Rate	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.	Baseline up to 7 days post-last dose of study medication
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Multiple-Dose Analysis	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.	Pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose on Day 8
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: Single-Dose Analysis	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.	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Maximum Observed Plasma Concentration (Cmax): Multiple-Dose Analysis	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.	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Maximum Observed Plasma Concentration (Cmax): Single-Dose Analysis	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.	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Time to Reach Maximum Observed Plasma Concentration (Tmax): Multiple-Dose Analysis	Tmax for participants who received pregabalin from Day 1 to Day 8 morning is reported (multiple-dose participants).	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Time to Reach Maximum Observed Plasma Concentration (Tmax): Single-Dose Analysis	Tmax for participants who received matching placebo from Day 1 to Day 7 and pregabalin on Day 8 morning is reported (single-dose participants).	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Plasma Decay Half-Life (t1/2): Multiple-Dose Analysis	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).	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Plasma Decay Half-Life (t1/2): Single-Dose Analysis	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).	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Apparent Oral Clearance (CL/F): Multiple-Dose Analysis	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).	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Apparent Oral Clearance (CL/F): Single-Dose Analysis	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).	Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8
Renal Clearance (CLr): Multiple-Dose Analysis	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).	0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8
Renal Clearance (CLr): Single-Dose Analysis	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).	0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Mann D, Liu J, Chew ML, Bockbrader H, Alvey CW, Zegarac E, Pellock J, Pitman VW. Safety, tolerability, and pharmacokinetics of pregabalin in children with refractory partial seizures: a phase 1, randomized controlled study. Epilepsia. 2014 Dec;55(12):1934-43. doi: 10.1111/epi.12830. Epub 2014 Nov 6.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: February 16, 2007
• First Submitted That Met QC Criteria: February 16, 2007
• First Posted (Estimate): February 19, 2007

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Partial-onset seizures; epilepsy; pediatric; pregabalin; safety; tolerability; pharmacokinetics
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Epilepsies, Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081074