Trial Outcomes & Findings for A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice (NCT NCT00855738)

Results Overview

Responder = decrease in number of seizures by \>=50 percent (%) during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the number of seizures that occurred during the 3 months before the baseline visit (baseline).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

111 participants

Primary outcome timeframe

Baseline, Month 3, Month 6 (last 3 months of treatment)

Results posted on

2021-01-25

Participant Flow

Given the observational nature of the study, the selection of treatment and dose of study medication was independent from participation in the study and was determined by daily clinical practice.

Participant milestones

Participant milestones
Measure	All Antiepileptic Drugs Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Overall Study STARTED	111
Overall Study At Least 1 Dose and 1 Endpoint	108
Overall Study COMPLETED	106
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	All Antiepileptic Drugs Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Overall Study Lost to Follow-up	2
Overall Study Adverse Event	1
Overall Study Subject Defaulted	1
Overall Study Death	1

Baseline Characteristics

A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Antiepileptic Drugs n=111 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Age, Continuous	45.3 years STANDARD_DEVIATION 16.1 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 3, Month 6 (last 3 months of treatment)

Population: Full Analysis Set (FAS): intent-to-treat population = those who took at least 1 dose of study medication and had post-baseline data for at least 1 efficacy endpoint. Last Observation Carried Forward (LOCF) captures last 3 months of treatment for subjects who discontinued between Month 3 and Month 6 only. N=number of subjects with evaluable data.

Responder = decrease in number of seizures by \>=50 percent (%) during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the number of seizures that occurred during the 3 months before the baseline visit (baseline).

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=90 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants Classified as Responders Month 3	76.7 percent of participants Interval 66.6 to 84.9
Percent of Participants Classified as Responders Month 6	80.0 percent of participants Interval 70.2 to 87.7

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6 (last 3 months of treatment)

Population: FAS; LOCF. N=number of subjects with evaluable data.

Percent of participants with reduction in number of seizures \>=25% and \>=75% during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the 3 month period before the baseline visit.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=90 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment Month 3: >=25%	86.7 percent of participants Interval 77.9 to 92.9
Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment Month 3: >=75%	27.8 percent of participants Interval 18.8 to 38.2
Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment Month 6: >= 25%	86.7 percent of participants Interval 77.9 to 92.9
Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment Month 6: >=75%	54.4 percent of participants Interval 43.6 to 65.0

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6 (last 3 months of treatment)

Population: FAS; LOCF. N=number of subjects with evaluable data.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=90 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation Month 3	10.0 percent of participants Interval 4.7 to 18.1
Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation Month 6	20.0 percent of participants Interval 12.3 to 29.8

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6 (last 3 months of treatment)

Population: FAS LOCF. N=number of subjects with evaluable data.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=90 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent Change From Baseline in the Median Number of Seizures During the Last 3 Months of Treatment	-75.0 percent change Interval -88.9 to -50.0

SECONDARY outcome

Timeframe: Baseline through Month 6 (or end of treatment)

Population: The percentage of days without crisis during the study was not evaluable because a diary with the daily number of crises was not collected.

Crisis was defined as the total number of seizures during the study, the seizures at month 3 plus the seizures at month 6. The percent of days without crisis is number of days of study (date of last visit minus date of baseline visit) without crisis divided by number of days of study, multiplied by 100.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 6 (or end of treatment)

Population: FAS LOCF. N=number of subjects with evaluable data.

Number of days to first seizure after baseline.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=79 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Time to First Seizure	35.9 days Standard Deviation 40.2

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS; LOCF.

Retention rate: percent of participants who continued on study medication throughout the 6 Month period after inclusion in the study.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=108 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants Who Continued on Study Medication to Month 6	97.1 percent of participants

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6

Population: FAS; LOCF. As no participants discontinued due to lack of efficacy, the time to exit analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6

Population: FAS; LOCF. Due to the low number of participants who discontinued due to safety, tolerability or compliance with treatment, the time to exit analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6

Population: FAS; LOCF. Due to the low number of participants who discontinued due to other reasons, the time to exit analyses was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6

Population: FAS; LOCF. The scale for this endpoint was not collected and results were not analyzed as planned.

Patient Global Impression of Change VAS: subject rated instrument to measure subject's change in overall status; range from 0 (much better) to 10 (much worse).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through Month 6 (or end of study)

Population: FAS; LOCF. N=number of participants who started on bitherapy.

Percent of participants who started on more than one treatment (bitherapy) and reached monotherapy by end of study.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=105 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants Reaching Monotherapy	2.9 percent of partipants Interval 0.6 to 8.1

SECONDARY outcome

Timeframe: Baseline to Month 6 (or end of treatment)

Population: FAS; LOCF.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=108 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) Reduced	0.9 percent of participants Interval 0.0 to 5.1
Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) Maintained	68.5 percent of participants Interval 58.9 to 77.1
Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) Increased	30.6 percent of participants Interval 22.1 to 40.2

SECONDARY outcome

Timeframe: Baseline through Month 6 (or end of treatment)

Population: FAS; LOCF. N= number of subjects with initial treatment administered as monotherapy.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=3 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy Reduced	0.0 percent of participants
Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy Maintained	100.0 percent of participants
Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy Increased	0.0 percent of participants

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS; LOCF. N=number of subjects with evaluable data.

HADS: subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=92 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS) Depression	-0.5 scores on scale Standard Deviation 3.5
Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS) Anxiety	-0.6 scores on scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS; LOCF. N=number of subjects with evaluable data.

QOLIE-10: 10-item questionnaire evaluates health-related quality of life in individuals with epliepsy. Comprised of 7 components: seizure worry, overall quality of life, emotional well-being, energy, cognitive functioning, medication effects (physical and mental effects), and social function (work, driving, social function). Total score rated 0 to 100; higher score = higher quality of life.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=107 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Energy	0.4 scores on scale Standard Deviation 17.8
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Emotions (mood)	0.7 scores on scale Standard Deviation 16.0
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Daily activities	0.6 scores on scale Standard Deviation 12.9
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Mental function	1.2 scores on scale Standard Deviation 20.8
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Medication effects (physical/ mental)	-1.1 scores on scale Standard Deviation 14.9
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Worry about seizures (impact of seizures)	9.0 scores on scale Standard Deviation 21.1
Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) Overall quality of life	3.8 scores on scale Standard Deviation 17.2

SECONDARY outcome

Timeframe: Baseline, Month 3, Month 6

Population: FAS LOCF. N=number of subjects with evaluable data.

Assessment of the health condition of the subjects using the EQ-5D VAS: subject rated questionnaire to assess health-related quality of life in terms of a single index value. Using the VAS subjects rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=105 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS) Month 3	-0.4 scores on scale Standard Deviation 16.2
Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS) Month 6	1.2 scores on scale Standard Deviation 15.6

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS LOCF. Change from baseline in Optimal sleep is not shown as changes from baseline were only evaluated for continuous parameters. N=number of subjects with evaluable data.

Subject rated instrument to assess key constructs of sleep; assesses sleep quality and quantity. Consists of a 6-item and 9-item overall sleep problems index measuring time to fall asleep and sleep duration in past 4 weeks; 5 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath, somnolence, and adequacy. Transformed scores range = 0 to 100; higher score indicates greater intensity of attribute. Two additional subscales = sleep quantity (range 0-24 hours) and optimal sleep (number of participants with optimal sleep 7-8 hours per night).

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=107 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Sleep disturbance	-1.7 scores on scale Standard Deviation 15.1
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Snoring	0.0 scores on scale Standard Deviation 15.6
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Awake short of breath	1.1 scores on scale Standard Deviation 14.6
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Quantity	0.2 scores on scale Standard Deviation 0.8
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Adequacy	2.8 scores on scale Standard Deviation 15.0
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Somnolence	0.6 scores on scale Standard Deviation 11.0
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Sleep problems (summary 6)	-0.9 scores on scale Standard Deviation 11.7
Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) Sleep problems (summary 9)	-0.9 scores on scale Standard Deviation 13.2

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: FAS; LOCF.

MOS-SS: subject rated instrument used to assess the key constructs of sleep; assesses sleep quantity and quality and is comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Optimal sleep subscale is derived from sleep quantity average hours of sleep over the past 4 weeks; percent of participants with response YES (optimal) if sleep quantilty was 7-8 hours of sleep per night.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=108 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS) Baseline	56.5 percent of participants
Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS) Month 6	65.7 percent of participants

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS; LOCF. Costs involved in health and non-health resources needed during the study were not analyzed as planned with this endpoint. N=number of subjects with visits to a specialist because of epilepsy.

Numerical assessment of change in the number of visits to a specialist or the emergency room because of epilepsy needed during the study.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=108 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy Number of visits to a specialist (n=94)	-0.6 visits Standard Deviation 2.3
Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy Number of visits to the emergency room (n=79)	-0.3 visits Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: FAS; LOCF. N=number of subjects with evaluable data.

Numerical assessment of change in total number of days hospitalized because of epilepsy during the study.

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=76 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Change From Baseline to Month 6 in Total Number of Days Hospitalized Because of Epilepsy	-8.0 Days Standard Deviation 68.6

SECONDARY outcome

Timeframe: Month 6

Population: FAS; LOCF.

Percent of participants with cessation of usual occupation, requirement of an informal caregiver, and who required admission to the intensive care unit (ICU).

Outcome measures

Outcome measures
Measure	All Antiepileptic Drugs n=108 Participants Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin: treatment, dose and frequency of administration determined by daily clinical practice
Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit Stopped Usual Occupation	16.2 percent of participants
Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit Required Informal Caregiver	6.6 percent of participants
Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit Required Admission to ICU	0.0 percent of participants

Adverse Events

All Antiepileptic Drugs (Including Pregabalin)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Pregabalin (Pregabalin Only)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	All Antiepileptic Drugs (Including Pregabalin) n=111 participants at risk Pregabalin, Levetiracetam, Topiramate, Lamotrigine, Oxcarbazepine, Zonisamide, Gabapentin	Pregabalin (Pregabalin Only) n=40 participants at risk
General disorders Asthenia	0.90% 1/111 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.	0.00% 0/40 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.
Investigations Weight increased	1.8% 2/111 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.	5.0% 2/40 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.
Nervous system disorders Dizziness	0.90% 1/111 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.	2.5% 1/40 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.
Nervous system disorders Somnolence	3.6% 4/111 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.	7.5% 3/40 • Includes data from baseline to 7 days after last dose of study drug. Safety Population: subjects known to have taken at least one dose of study medication.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER