Efficacy And Safety Study Of Pregabalin (Lyrica) As Monot... | NCT00524030

NCT00524030

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
1	Experimental		Drug: pregabalin 600 mg/day
2	Experimental		Drug: pregabalin 150 mg/day

Name	Type	Description	Arm Group Labels	Other Names
pregabalin 600 mg/day	Drug	pregabalin 600 mg/day (300mg BID), duration is 20 weeks.	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants in the Pregabalin 600 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria	Participants who discontinued due to: episode of status epilepticus (SE); secondarily generalized tonic-clonic (SGTC) seizure if none within 2 years of study entry; 28-day study seizure rate during double-blind phase (DBP) greater than (>)2 times maximum (Max) 28-day study seizure rate during baseline phase (BLP); 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate:(1-Kaplan-Meier [KM] product limit estimate for survival function) * 100%	Week 2 up to Week 18

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants in the Pregabalin 150 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria	Participants who discontinued due to: episode of SE; SGTC seizure if none within 2 years of study entry; 28-day study seizure rate during DBP >2 times Max 28-day study seizure rate during BLP; 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate, defined as (1-KM product limit estimate for survival function) * 100%

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Northport	Alabama	35476	United States
Pfizer Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24415567	Derived	French J, Kwan P, Fakhoury T, Pitman V, DuBrava S, Knapp L, Yurkewicz L. Pregabalin monotherapy in patients with partial-onset seizures: a historical-controlled trial. Neurology. 2014 Feb 18;82(7):590-7. doi: 10.1212/WNL.0000000000000119. Epub 2014 Jan 10.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
BG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00031.9(20.7 to 43.1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Null hypothesis (H0): Exit rate greater than or equal to (≥)74%	Wald Test	2-sided 95% adjusted confidence interval constructed using KM product limit estimation and Greenwood's formula for variance with continuity correction	<0.001						2-Sided								Superiority or Other (legacy)
OG000

Secondary

Percentage of Participants in the Pregabalin 150 mg/Day Treatment Group Discontinuing the Study Due to at Least 1 Pre-Defined Seizure Exit Criteria

Participants who discontinued due to: episode of SE; SGTC seizure if none within 2 years of study entry; 28-day study seizure rate during DBP >2 times Max 28-day study seizure rate during BLP; 2-day study seizure rate during DBP >2 times Max 2-day study seizure rate during BLP; or unacceptable clinically significant increase in frequency/intensity of seizure activity. Determined as exit rate, defined as (1-KM product limit estimate for survival function) * 100%

MITT Full Study Set: all randomized participants who met the MITT definition (received at least 1 dose of pregabalin in DB treatment phase, had BL seizure assessment, and participated in DB efficacy assessment after Week 2)

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 2 up to Week 18

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.

Units	Counts
Participants

Secondary

Percentage of Participants Completing 20 Weeks of Double-Blind Treatment

MITT Full Study Set

Posted

Number

Percentage of Participants

Randomization up to Week 20

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
OG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.

Units	Counts
Participants

Secondary

Percentage of Participants Who Met Protocol-Specified Exit Events

Percentage of participants experiencing any of the following (could have had more than 1): 1) episode of SE; 2) SGTC seizure if none had been experienced within 2 years of study entry; 3) 28-day study seizure rate during DBP >2 times the Max 28-day study seizure rate during BLP; 4) 2-day study seizure rate during the DBP >2 times the Max 2-day study seizure rate during BLP; or 5) unacceptable clinically significant increase in frequency/intensity of seizure activity

MITT Efficacy Set

Posted

Number

Percentage of Participants

Week 2 up to Week 18

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
OG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.

Secondary

Mean Time on Pregabalin Monotherapy

MITT Full Study Set; N=number of participants entering Monotherapy Period

Posted

Mean

Standard Deviation

Days

Week 2 to Week 20

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
OG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.

Units	Counts
Participants

Secondary

Percentage of Seizure-Free Participants by Study Phase

Percentage of participants who were seizure-free during the last 28 days on double-blind study medication (monotherapy phase, Days 112-140), during the monotherapy portion of the double-blind treatment phase (Days 56-140), and during all of the double-blind treatment phase (Days 1-140)

MITT Full Study Set

Posted

Number

Percentage of Participants

Day 1 up to Day 140

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
OG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.

Secondary

Pregabalin Population Pharmacokinetics (PK)

Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Posted

Baseline up to 20 weeks

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
OG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.

Secondary

Pregabalin Exposure-Response Analysis

Percentage of participants predicted to exit the study due to any seizure exit criteria at Day 126. The exit rate at Day 126 was predicted using the final model (log normal distribution with respect to treatment group) and the parameter estimates.

MITT Full Study Set

Posted

Number

Percentage of Participants

Day 126

ID	Title	Description
OG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.
OG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.

Units	Counts

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pregabalin 150 mg/Day	Pregabalin 75 milligram (mg) capsules, administered orally twice daily (BID), for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (antiepileptic drug [AED] taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase.			1	32	15	32
EG001	Pregabalin 600 mg/Day	Pregabalin 300 mg capsules, administered orally, BID for up to a 20-week Double-Blind Treatment Phase, which included an 8-week conversion period (2-week pregabalin dose escalation/6-week AED taper) and a 12-week pregabalin Monotherapy Period, followed by a 1-week Titration/Taper phase. Dose escalation to 600 mg/day occurred over 2 weeks as follows: 75 mg BID on Days 1-7, 150 mg BID on Days 8-14, and 300 mg BID from Day 15 up to Week 20.			17	129	75	129

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Chest pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Meningitis bacterial	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected129 at risk
Complex partial seizures	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Convulsion	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0015 affected129 at risk
Epilepsy	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Grand mal convulsion	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0012 affected129 at risk
Lethargy	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Status epilepticus	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 14.0	Systematic Assessment	EG0001 affected32 at risk EG0010 affected129 at risk
Homicidal ideation	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0011 affected129 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vision blurred	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected32 at risk EG0018 affected129 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected129 at risk
Flatulence	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0018 affected129 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected32 at risk EG00120 affected129 at risk
Oedema peripheral	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected32 at risk EG0018 affected129 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0002 affected32 at risk EG0011 affected129 at risk
Weight increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0002 affected32 at risk EG00121 affected129 at risk
Balance disorder	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0018 affected129 at risk
Disturbance in attention	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected32 at risk EG0014 affected129 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0005 affected32 at risk EG00125 affected129 at risk
Dysarthria	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected32 at risk EG0012 affected129 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG00113 affected129 at risk
Somnolence	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0005 affected32 at risk EG00122 affected129 at risk
Confusional state	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected32 at risk EG0017 affected129 at risk

External Data Monitoring Committee (DMC) determined study met criteria to stop early for positive efficacy. Exit rate was the basis for primary analysis and is what is reported here.

Certain Agreements

ID	Term
D004828	Epilepsies, Partial
D004827	Epilepsy
D012640	Seizures

Ancestor Terms

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000069583	Pregabalin

Ancestor Terms

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins

H0: Exite rate ≥68%