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

Phase 1
Completed
Conditions
Epilepsies, Partial
Interventions
Drug: Placebo
Registration Number
NCT00437281
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
65
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
PregabalinPregabalin-
Primary Outcome Measures
NameTimeMethod
Number of Treatment-Emergent Adverse Events (AEs) by Severity: Open-label TreatmentDay 8 up to 28 days after open-label dose of study medication

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.

Number of Treatment-Emergent Adverse Events (AEs) by Severity: Double-blind TreatmentBaseline to Day 7

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.

Secondary Outcome Measures
NameTimeMethod
Maximum Observed Plasma Concentration (Cmax): Multiple-Dose AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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 Analysis0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8

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 Analysis0 to 12 hours post-dose, 12 to 24 hours post-dose on Day 8

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).

Number of Participants With Clinically Significant Change in Physical and Neurological FindingsBaseline up to 7 days post-last dose of study medication

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.

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: Single-Dose AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 8

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.

28-Day Seizure Frequency RateBaseline up to 7 days post-last dose of study medication

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 AnalysisPre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose on Day 8

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.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇲🇽

Guadalajara, Jalisco, Mexico

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