Trial Outcomes & Findings for A Safety, Efficacy and Tolerability Trial of Pregabalin as Add-On Treatment in Pediatric and Adult Subjects With Primary Generalized Tonic-Clonic (i.e., Grand Mal) Seizures. (NCT NCT01747915)

Last Updated: 2021-01-20

Results Overview

All PGTC seizures experienced during treatment phase were recorded by the participants or their parents/legal guardian in a daily seizure diary. 28-day seizure rate for all PGTC seizures= (\[number of seizures in the double blind treatment phase\] divided by \[number of days in double blind treatment phase minus {-} number of missing diary days in treatment phase\])\*28. For log-transformation, the quantity 1 was added to the 28-day seizure rate for all participants to account for any possible "0" seizure incidence. This resulted in final calculation as: log transformed (28-day seizure rate +1).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

219 participants

Primary outcome timeframe

Day 1 up to Week 12

Results posted on

2021-01-20

Participant Flow

The study was conducted at multiple sites in 21 countries in 219 participants between 03 April 2013 and 20 February 2019.

Participant milestones

Participant milestones
Measure	Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day Participants aged less than (\<) 17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight greater than or equal to (\>=)30 kg: Pregabalin 5 milligram per kilogram per day (mg/kg/day) as capsule or oral solution (using oral solution of strength 20 milligram per milliliter \[mg/mL\]), up to a maximum of 300 milligram per day (mg/day); 2) body weight \<30 kg: pregabalin 7 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 300 mg/day. Participants aged \>=17 years received Pregabalin 300 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day Participants aged \<17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight \>=30 kg: Pregabalin 10 mg/kg/day as capsule or oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day; 2) body weight \<30 kg: pregabalin 14 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day. Participants aged \>=17 years received Pregabalin 600 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Placebo Participants aged \<17 years received placebo matched to Pregabalin, orally, twice daily for the double-blind treatment phase of 12 weeks (in the form of solution for \<30 kg participants; in the form of capsule or liquid oral solution for \>=30 kg participants). Participants aged \>=17 years received placebo matched to Pregabalin, in the form of capsule or liquid oral solution, orally, twice daily for the double-blind treatment phase of 12 weeks.
Overall Study STARTED	75	72	72
Overall Study COMPLETED	60	61	66
Overall Study NOT COMPLETED	15	11	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day Participants aged less than (\<) 17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight greater than or equal to (\>=)30 kg: Pregabalin 5 milligram per kilogram per day (mg/kg/day) as capsule or oral solution (using oral solution of strength 20 milligram per milliliter \[mg/mL\]), up to a maximum of 300 milligram per day (mg/day); 2) body weight \<30 kg: pregabalin 7 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 300 mg/day. Participants aged \>=17 years received Pregabalin 300 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day Participants aged \<17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight \>=30 kg: Pregabalin 10 mg/kg/day as capsule or oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day; 2) body weight \<30 kg: pregabalin 14 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day. Participants aged \>=17 years received Pregabalin 600 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Placebo Participants aged \<17 years received placebo matched to Pregabalin, orally, twice daily for the double-blind treatment phase of 12 weeks (in the form of solution for \<30 kg participants; in the form of capsule or liquid oral solution for \>=30 kg participants). Participants aged \>=17 years received placebo matched to Pregabalin, in the form of capsule or liquid oral solution, orally, twice daily for the double-blind treatment phase of 12 weeks.
Overall Study Other	1	1	1
Overall Study Adverse Event	8	5	2
Overall Study Death	0	0	1
Overall Study Lack of Efficacy	0	1	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Withdrawal by Subject	4	4	1
Overall Study Protocol Violation	1	0	0
Overall Study Pregnancy	0	0	1

Baseline Characteristics

A Safety, Efficacy and Tolerability Trial of Pregabalin as Add-On Treatment in Pediatric and Adult Subjects With Primary Generalized Tonic-Clonic (i.e., Grand Mal) Seizures.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day n=75 Participants Participants aged less than (\<) 17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight greater than or equal to (\>=)30 kg: Pregabalin 5 milligram per kilogram per day (mg/kg/day) as capsule or oral solution (using oral solution of strength 20 milligram per milliliter \[mg/mL\]), up to a maximum of 300 milligram per day (mg/day); 2) body weight \<30 kg: pregabalin 7 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 300 mg/day. Participants aged \>=17 years received Pregabalin 300 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day n=72 Participants Participants aged \<17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight \>=30 kg: Pregabalin 10 mg/kg/day as capsule or oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day; 2) body weight \<30 kg: pregabalin 14 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day. Participants aged \>=17 years received Pregabalin 600 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Placebo n=72 Participants Participants aged \<17 years received placebo matched to Pregabalin, orally, twice daily for the double-blind treatment phase of 12 weeks (in the form of solution for \<30 kg participants; in the form of capsule or liquid oral solution for \>=30 kg participants). Participants aged \>=17 years received placebo matched to Pregabalin, in the form of capsule or liquid oral solution, orally, twice daily for the double-blind treatment phase of 12 weeks.	Total n=219 Participants Total of all reporting groups
Age, Continuous	24.0 years STANDARD_DEVIATION 13.3 • n=5 Participants	25.4 years STANDARD_DEVIATION 12.7 • n=7 Participants	26.2 years STANDARD_DEVIATION 13.2 • n=5 Participants	25.2 years STANDARD_DEVIATION 13.1 • n=4 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	39 Participants n=7 Participants	40 Participants n=5 Participants	121 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	33 Participants n=7 Participants	32 Participants n=5 Participants	98 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	67 Participants n=5 Participants	64 Participants n=7 Participants	65 Participants n=5 Participants	196 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 up to Week 12

Population: ITT population included all randomized participants who took at least 1 dose of investigational product during the double-blind treatment phase, have a baseline value and at least 1 post-baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day n=75 Participants Participants aged less than (\<) 17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight greater than or equal to (\>=)30 kg: Pregabalin 5 milligram per kilogram per day (mg/kg/day) as capsule or oral solution (using oral solution of strength 20 milligram per milliliter \[mg/mL\]), up to a maximum of 300 milligram per day (mg/day); 2) body weight \<30 kg: pregabalin 7 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 300 mg/day. Participants aged \>=17 years received Pregabalin 300 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day n=72 Participants Participants aged \<17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight \>=30 kg: Pregabalin 10 mg/kg/day as capsule or oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day; 2) body weight \<30 kg: pregabalin 14 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day. Participants aged \>=17 years received Pregabalin 600 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Placebo n=72 Participants Participants aged \<17 years received placebo matched to Pregabalin, orally, twice daily for the double-blind treatment phase of 12 weeks (in the form of solution for \<30 kg participants; in the form of capsule or liquid oral solution for \>=30 kg participants). Participants aged \>=17 years received placebo matched to Pregabalin, in the form of capsule or liquid oral solution, orally, twice daily for the double-blind treatment phase of 12 weeks.
Log-transformed (Log) 28-day Seizure Rate for All Primary Generalized Tonic-Clonic (PGTC) Seizures During 12-Week Double-Blind Treatment Phase	1.17 Seizure per 28 days Standard Error 0.097	1.13 Seizure per 28 days Standard Error 0.095	1.14 Seizure per 28 days Standard Error 0.098

SECONDARY outcome

Timeframe: Day 1 up to Week 12

Percentage of participants with 50% or greater reduction from baseline in 28-day seizure rate during the 12 week double blind treatment phase were reported. 28-day seizure rate for all PGTC seizures= (\[number of seizures in the double blind treatment phase\] divided by \[number of days in double blind treatment phase minus {-} number of missing diary days in treatment phase\])\*28.

Outcome measures

Outcome measures
Measure	Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day n=75 Participants Participants aged less than (\<) 17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight greater than or equal to (\>=)30 kg: Pregabalin 5 milligram per kilogram per day (mg/kg/day) as capsule or oral solution (using oral solution of strength 20 milligram per milliliter \[mg/mL\]), up to a maximum of 300 milligram per day (mg/day); 2) body weight \<30 kg: pregabalin 7 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 300 mg/day. Participants aged \>=17 years received Pregabalin 300 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day n=72 Participants Participants aged \<17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight \>=30 kg: Pregabalin 10 mg/kg/day as capsule or oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day; 2) body weight \<30 kg: pregabalin 14 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day. Participants aged \>=17 years received Pregabalin 600 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Placebo n=72 Participants Participants aged \<17 years received placebo matched to Pregabalin, orally, twice daily for the double-blind treatment phase of 12 weeks (in the form of solution for \<30 kg participants; in the form of capsule or liquid oral solution for \>=30 kg participants). Participants aged \>=17 years received placebo matched to Pregabalin, in the form of capsule or liquid oral solution, orally, twice daily for the double-blind treatment phase of 12 weeks.
Percentage of Participants With at Least 50 Percent (%) or Greater Reduction From Baseline in 28-day Primary Generalized Tonic-clonic (PGTC) Seizure Rate During the 12-Week Double-blind Treatment Phase	41.3 percentage of participants	38.9 percentage of participants	41.7 percentage of participants

Adverse Events

Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 36 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin 5 mg/kg/Day or 7 mg/kg/Day or 300 mg/Day n=75 participants at risk Participants aged less than (\<) 17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight greater than or equal to (\>=)30 kg: Pregabalin 5 milligram per kilogram per day (mg/kg/day) as capsule or oral solution (using oral solution of strength 20 milligram per milliliter \[mg/mL\]), up to a maximum of 300 milligram per day (mg/day); 2) body weight \<30 kg: pregabalin 7 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 300 mg/day. Participants aged \>=17 years received Pregabalin 300 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Pregabalin 10 mg/kg/Day or 14 mg/kg/Day or 600 mg/Day n=72 participants at risk Participants aged \<17 years received Pregabalin, orally, twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks in following manner: 1) body weight \>=30 kg: Pregabalin 10 mg/kg/day as capsule or oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day; 2) body weight \<30 kg: pregabalin 14 mg/kg/day as oral solution (using oral solution of strength 20 mg/mL), up to a maximum of 600 mg/day. Participants aged \>=17 years received Pregabalin 600 mg/day, capsule or oral solution, orally twice daily in equally divided doses, for the double-blind treatment phase of 12 weeks.	Placebo n=72 participants at risk Participants aged \<17 years received placebo matched to Pregabalin, orally, twice daily for the double-blind treatment phase of 12 weeks (in the form of solution for \<30 kg participants; in the form of capsule or liquid oral solution for \>=30 kg participants). Participants aged \>=17 years received placebo matched to Pregabalin, in the form of capsule or liquid oral solution, orally, twice daily for the double-blind treatment phase of 12 weeks.
Nervous system disorders Generalised tonic-clonic seizure	1.3% 1/75 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	2.8% 2/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	0.00% 0/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
General disorders Sudden unexplained death in epilepsy	0.00% 0/75 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	0.00% 0/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	1.4% 1/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
Nervous system disorders Seizure	0.00% 0/75 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	0.00% 0/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	2.8% 2/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.
Nervous system disorders Status epilepticus	1.3% 1/75 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	0.00% 0/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.	0.00% 0/72 • Day 1 up to end of study (Week 13) Same event may appear as adverse event (AE) and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study.

Other adverse events

Additional Information

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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.
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