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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Placebo

Pregabalin

About this trial

This is an interventional treatment trial for Epilepsies, Partial focused on measuring Partial-onset seizures; epilepsy; pediatric; pregabalin; safety; tolerability; pharmacokinetics

Eligibility Criteria

1 Month - 16 Years (Child)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Pregabalin

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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).

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).

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).

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).

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).

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).

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).

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).

Full Information

NCT ID

NCT00437281

First Posted

February 16, 2007

Last Updated

January 26, 2021

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT00437281

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2014

Overall Recruitment Status

Completed

Study Start Date

April 2007 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsies, Partial

Keywords

Partial-onset seizures; epilepsy; pediatric; pregabalin; safety; tolerability; pharmacokinetics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Title

Pregabalin

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Pregabalin

Intervention Description

Orally-administered pregabalin

Primary Outcome Measure Information:

Title

Number of Treatment-Emergent Adverse Events (AEs) by Severity: Double-blind Treatment

Description

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.

Time Frame

Baseline to Day 7

Title

Number of Treatment-Emergent Adverse Events (AEs) by Severity: Open-label Treatment

Description

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.

Time Frame

Day 8 up to 28 days after open-label dose of study medication

Secondary Outcome Measure Information:

Title

Number of Participants With Clinically Significant Change in Physical and Neurological Findings

Description

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.

Time Frame

Baseline up to 7 days post-last dose of study medication

Title

28-Day Seizure Frequency Rate

Description

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.

Time Frame

Baseline up to 7 days post-last dose of study medication

Title

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Multiple-Dose Analysis

Description

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.

Time Frame

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

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: Single-Dose Analysis

Description

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.

Time Frame