Complex Partial Seizure Disorder, Epilepsies, Partial, Epilepsy, Partial Seizure Disorder
Conditions
Brief summary
To compare the efficacy of pregabalin and gabapentin, as adjunctive therapy in subjects with partial seizures.
Interventions
DRUGPregabalin
150, 300, 450 mg/day administered orally TID, until seizure control/improvement or intolerable side effects
DRUGGabapentin
300, 600, 1200, 2000 mg/day administered orally TID, until seizure control/improvement or intolerable side effects
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects (male or female) must be \> 18 years or ≤ 80 years of age, with a diagnosis of epilepsy with partial seizures, as defined in the International League Against Epilepsy (ILAE) classification of seizures; partial seizures may be simple or complex, with or without secondary tonic-clonic generalization. * Subjects must be have been diagnosed with epilepsy for at least 2 years, and must have been unresponsive to treatment with at least two but no more than five prior antiepileptic drugs (AEDs), and at the time of study enrollment are on stable dosages of 1 or 2 standard AEDs. * They must have had a 12 lead electrocardiogram (ECG) without clinically significant abnormal findings prior to randomization. * Subjects must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy. * Women of childbearing potential must be established on an effective method of contraception during the study. Women should also have a negative pregnancy test prior to study entry. * During the 6-week baseline period, subjects must have had a minimum of four partial seizures, with no 28 day period free of partial seizures with or without secondary generalization. A caregiver or witness must be with the subject for a sufficient duration to accurately chronicle the occurrence of seizures. These seizures must have been documented in the subject's diary. * Subjects with electroencephalograph (EEG) testing done within 2 years of randomization. EEG abnormalities should be consistent with a diagnosis of focal-onset epilepsy. * Signed and dated informed consent will be obtained from each subject (only include those able to consent) in accordance with the local regulatory and legal requirements. * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Subjects who are willing, but need assistance for self administered questionnaires may be considered acceptable, but must first be discussed on a case-by-case basis with the Pfizer monitor prior to any to any screening tests or procedures for the study.
Exclusion criteria
* Females who are pregnant, breastfeeding, or intending to become pregnant during the course of the trial. * Subjects with other neurologic illness that could impair endpoint assessment, or patients with Lennox-Gastaut syndrome, absence seizures, status epilepticus within the 12 months prior to study entry, or with seizures due to an underlying medical illness or metabolic syndrome. * Subjects with clinically significant liver disease or with a calculated creatinine clearance of \<60mL/min. * Subjects with a history of lack of response, hypersensitivity or poor tolerability to gabapentin or pregabalin. * Previous use of gabapentin or pregabalin within 2 weeks prior to screening or likelihood of engaging in these treatments during the study period. * Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol. * Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study. * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial. * Subjects who are not suitable to be treated with pregabalin or gabapentin according to the respective local labeling. * Subjects with a history of retinal abnormalities or treatment with retinotoxic agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in 28-day Seizure Frequency at Week 21. | 6 weeks Baseline, 21 weeks through End of MP for 27 weeks | The seizures were recorded by the participants, by a family member, by a caregiver, or by a legal guardian and documented in a daily seizure diary. Participant's 28-day seizure frequency of all partial seizure was assessed during double blind (TP + MP) phase compared with baseline. Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + secondary generalized tonic clonic seizure \[SGTC\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | 6 weeks Baseline, 21 weeks through End of MP for 27 weeks | Participants who had at least 75% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 75% responders. If percent change from baseline \<= -75 then 75% responder rate = 1 (yes) otherwise responder rate = 0 (no). Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + SGTC). |
| Percentage of Participants Without Seizures. | 6 weeks Baseline, 21 weeks through End of MP for 27 weeks | Seizure free for 28 days was defined as participants who have not experienced any seizure (simple partial, complex partial and SGTC) for at least 28 consecutive days from their last seizure until the end of the MP. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure. |
| Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21. | 6 weeks Baseline, 21 weeks through End of MP for 27 weeks | Change in SGTC = (Proportion of SGTC/All Partial Seizure rate during at the double-blind phase) - (Proportion of SGTC/All Partial Seizure rate at Baseline). Negative values indicate reduction from baseline. |
| Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | 6 weeks Baseline, 21 weeks through End of MP for 27 weeks | Participants who had at least 50% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 50% responders. If percent change from baseline \<= -50 then responder rate = 1 (yes) otherwise responder rate = 0 (no). |
| Hospital Anxiety and Depression Scale (HADS) Score. | Baseline, Week 21 | HADS: participant rated questionnaire with 2 subscales. Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (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. |
| Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline, Week 21 | Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range:0-100); sleep quantity (range:0-24), optimal sleep (yes/no), and 9 item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except adequacy, optimal sleep and quantity, higher scores=more impairment. Scores transformed (actual raw score \[RS\] minus lowest possible score divided by possible RS range\*100); total score range:0-100; higher score=more intensity of attribute. |
| Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score. | Baseline, Week 21 | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Percentage of participants with optimal sleep are reported. |
| Reduction in Proportion of the 28-day SGTC Seizure Rate Over the Total Partial Seizure Rate at Week 21. | 6 weeks Baseline, 21 weeks through End of MP for 27 weeks | SGTC Responder is defined as a participant who shows reduction from Baseline to double-blind phase in proportion of 28-Day SGTC Seizure Rate to 28-Day All Partial Seizure Rate. |
Countries
Costa Rica, El Salvador, Guatemala, Peru
Participant flow
Recruitment details
Overall, 561 participants were screened and 482 participants participated in the study; 242 participants were randomized but one participant from the pregabalin group and one participant from the gabapentin group were not treated. Hence 241 participants were treated in each treatment group. Participants were randomized at 56 centers.
Pre-assignment details
One participant from the pregabalin group and one participant from the gabapentin group were randomized but not treated.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Pregabalin was initiated at 150 mg/day \[50 mg capsules orally three times a day (TID)\] for 1 Week followed by pregabalin 300 mg/day (100 mg TID) orally TID up to Week 5 in the Titration Phase (TP). Participants who had adequate seizure control (adequate: \>=50% reduction in seizures) with acceptable tolerability with pregabalin 300 mg/day in TP, continued same dose until the end of TP (Week 9) and then entered the maintenance phase (MP) on this dose. If seizure control was inadequate, the pregabalin dose was escalated to 450 mg/day orally (150 mg TID) from Weeks 5 through 9. If the participants had adequate seizure control with acceptable tolerability on this dose, then they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 600 mg/day (200 mg TID) at which time they entered the MP. | 241 |
| Gabapentin Gabapentin was initiated at 300 mg/day \[100 mg capsules orally three times a day (TID)\] followed by gabapentin 600 mg/day (200 mg TID) on Day 3. At the end of Week 1 (Day 7), the dose was increased to 1200 mg/day (400 mg TID) and remained on this dose for the next 4 weeks). Participants who had adequate seizure control (\>=50% reduction in seizure frequency) with acceptable tolerability during this initial 5-week period, remained on this dose until the end of theTP (Week 9), then entered the MP on this dose. If seizure control was inadequate, the gabapentin dose was escalated to 1500 mg/day (500 mg TID) during Weeks 5 through 9. If they had adequate seizure control with acceptable tolerability on this dose, they entered the MP on this dose. If there was inadequate seizure control at the end of Week 9, the dose was escalated a final time to 1800 mg/day (600 mg TID), at which time they entered the MP. | 241 |
| Total | 482 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 20 | 19 |
| Overall Study | Lack of Efficacy | 8 | 16 |
| Overall Study | Lost to Follow-up | 23 | 29 |
| Overall Study | Other | 10 | 12 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Protocol Violation | 6 | 4 |
| Overall Study | Study terminated by sponsor | 2 | 3 |
| Overall Study | Withdrawal by Subject | 113 | 95 |
Baseline characteristics
| Characteristic | Pregabalin | Gabapentin | Total |
|---|---|---|---|
| Age, Continuous | 34.9 years STANDARD_DEVIATION 13 | 35.3 years STANDARD_DEVIATION 12.9 | 35.1 years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 114 Participants | 111 Participants | 225 Participants |
| Sex: Female, Male Male | 127 Participants | 130 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 241 | 77 / 241 |
| serious Total, serious adverse events | 13 / 241 | 14 / 241 |
Outcome results
Primary
Percent Change From Baseline in 28-day Seizure Frequency at Week 21.
The seizures were recorded by the participants, by a family member, by a caregiver, or by a legal guardian and documented in a daily seizure diary. Participant's 28-day seizure frequency of all partial seizure was assessed during double blind (TP + MP) phase compared with baseline. Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + secondary generalized tonic clonic seizure \[SGTC\]).
Time frame: 6 weeks Baseline, 21 weeks through End of MP for 27 weeks
Population: Full analysis set (FAS) included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pregabalin | Percent Change From Baseline in 28-day Seizure Frequency at Week 21. | -58.65 percent change |
| Gabapentin | Percent Change From Baseline in 28-day Seizure Frequency at Week 21. | -57.43 percent change |
Comparison: Rank analysis of covariance (ANCOVA) model was used to derive p-value with treatment as main effect and cluster as cofactor, percent change in 28-day seizure counts between Baseline and treatment periods as dependent variable. Median differences and 95% confidence interval (CI) were based on Hodges-Lehmann estimation.p-value: 0.870895% CI: [-6, 7]Ranked ANCOVA
Secondary
Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21.
Change in SGTC = (Proportion of SGTC/All Partial Seizure rate during at the double-blind phase) - (Proportion of SGTC/All Partial Seizure rate at Baseline). Negative values indicate reduction from baseline.
Time frame: 6 weeks Baseline, 21 weeks through End of MP for 27 weeks
Population: SGTC population included all participants who had at least 1 SGTC seizure during either Baseline or double-blind phase. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21. | Baseline (n=114, 114) | 56.53 percentage of all partial seizure/28days | Standard Deviation 40.856 |
| Pregabalin | Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21. | Change from Baseline at Double Blind (n=104, 98) | 1.59 percentage of all partial seizure/28days | Standard Deviation 28.164 |
| Gabapentin | Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21. | Baseline (n=114, 114) | 59.60 percentage of all partial seizure/28days | Standard Deviation 40.571 |
| Gabapentin | Change From Baseline in the 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Frequency at Week 21. | Change from Baseline at Double Blind (n=104, 98) | -2.17 percentage of all partial seizure/28days | Standard Deviation 26.024 |
Secondary
Hospital Anxiety and Depression Scale (HADS) Score.
HADS: participant rated questionnaire with 2 subscales. Hospital Anxiety and Depression Scale - anxiety (HADS-A) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); Hospital Anxiety and Depression Scale - depression (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.
Time frame: Baseline, Week 21
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. N (number of participants analyzed)=participants who were evaluable for this measure. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score. | Baseline HADS-A (n=238, 240) | 7.82 Units on a scale | Standard Error 0.31 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score. | HADS- A Change at Week 21/ET (n=212, 210) | -0.92 Units on a scale | Standard Error 0.26 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score. | Baseline HADS-D (n=238, 240) | 5.94 Units on a scale | Standard Error 0.29 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) Score. | HADS-D Change at Week 21/ET (n=212, 210) | -0.59 Units on a scale | Standard Error 0.24 |
| Gabapentin | Hospital Anxiety and Depression Scale (HADS) Score. | HADS-D Change at Week 21/ET (n=212, 210) | -0.42 Units on a scale | Standard Error 0.24 |
| Gabapentin | Hospital Anxiety and Depression Scale (HADS) Score. | Baseline HADS-A (n=238, 240) | 7.60 Units on a scale | Standard Error 0.31 |
| Gabapentin | Hospital Anxiety and Depression Scale (HADS) Score. | Baseline HADS-D (n=238, 240) | 5.65 Units on a scale | Standard Error 0.29 |
| Gabapentin | Hospital Anxiety and Depression Scale (HADS) Score. | HADS- A Change at Week 21/ET (n=212, 210) | -0.83 Units on a scale | Standard Error 0.27 |
Comparison: Baseline, HADS-A: ANCOVA model was used to calculate least square (LS) mean estimates of the treatment difference along with 95% CI, with main effects of treatment and and country as covariates.p-value: 0.564395% CI: [-0.53, 0.97]ANCOVA
Comparison: Change at Week 21 / ET , HADS-A: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country as covariates.p-value: 0.771295% CI: [-0.73, 0.54]ANCOVA
Comparison: Baseline, HADS-D: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.423695% CI: [-0.41, 0.97]Ranked ANCOVA
Comparison: Change at Week 21/ET, HADS-D: ANCOVA model was used to calculate LS mean estimates of the treatment1difference along with 95% CI, with main effects of treatment and combined center, and for post-baseline assessments baseline was included as a covariate.p-value: 0.549295% CI: [-0.75, 0.4]Ranked ANCOVA
Secondary
Medical Outcomes Study Sleep Scale (MOS-SS) Score.
Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence (range:0-100); sleep quantity (range:0-24), optimal sleep (yes/no), and 9 item index measures of sleep disturbance provide composite scores: sleep problem summary, overall sleep problem. Except adequacy, optimal sleep and quantity, higher scores=more impairment. Scores transformed (actual raw score \[RS\] minus lowest possible score divided by possible RS range\*100); total score range:0-100; higher score=more intensity of attribute.
Time frame: Baseline, Week 21
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. n=number of participants evaluable at specific time points for each arm group, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Sleep Disturbance (n=238, 240) | 29.68 Units on a scale | Standard Error 1.7 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Snoring (n=238, 240) | 29.28 Units on a scale | Standard Error 2.31 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Awaken Short of Breath (n=238, 240) | 23.64 Units on a scale | Standard Error 2.07 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Quantity of Sleep (n=238, 240) | 7.56 Units on a scale | Standard Error 0.11 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Adequacy of Sleep (n=238, 240) | 61.30 Units on a scale | Standard Error 2.01 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Somnolence (n=238, 240) | 32.29 Units on a scale | Standard Error 1.56 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Sleep Problem Index (9) (n=238, 240) | 31.60 Units on a scale | Standard Error 1.32 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Sleep Disturbance (n=212, 210) | 24.99 Units on a scale | Standard Error 1.37 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Snoring (n=212, 210) | 28.07 Units on a scale | Standard Error 1.89 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Awaken Short of Breath (n=212, 210) | 16.26 Units on a scale | Standard Error 1.73 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Quantity of Sleep (n=212, 210) | 8.79 Units on a scale | Standard Error 0.17 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Adequacy of Sleep (n=212, 210) | 63.87 Units on a scale | Standard Error 1.68 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Somnolence (n=212, 210) | 32.04 Units on a scale | Standard Error 1.36 |
| Pregabalin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Sleep Problem Index (9) (n=212, 210) | 27.88 Units on a scale | Standard Error 1.04 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Quantity of Sleep (n=212, 210) | 8.77 Units on a scale | Standard Error 0.17 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Sleep Disturbance (n=238, 240) | 26.43 Units on a scale | Standard Error 1.7 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Sleep Disturbance (n=212, 210) | 25.31 Units on a scale | Standard Error 1.39 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Snoring (n=238, 240) | 28.09 Units on a scale | Standard Error 2.31 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Somnolence (n=212, 210) | 29.98 Units on a scale | Standard Error 1.37 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Awaken Short of Breath (n=238, 240) | 19.61 Units on a scale | Standard Error 2.07 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Snoring (n=212, 210) | 26.12 Units on a scale | Standard Error 1.9 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Quantity of Sleep (n=238, 240) | 7.59 Units on a scale | Standard Error 0.11 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Adequacy of Sleep (n=212, 210) | 64.53 Units on a scale | Standard Error 1.69 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Adequacy of Sleep (n=238, 240) | 63.67 Units on a scale | Standard Error 2.01 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Awaken Short of Breath (n=212, 210) | 18.20 Units on a scale | Standard Error 1.74 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Somnolence (n=238, 240) | 29.31 Units on a scale | Standard Error 1.56 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Week 21: Sleep Problem Index (9) (n=212, 210) | 27.54 Units on a scale | Standard Error 1.05 |
| Gabapentin | Medical Outcomes Study Sleep Scale (MOS-SS) Score. | Baseline: Sleep Problem Index (9) (n=238, 240) | 28.15 Units on a scale | Standard Error 1.32 |
Comparison: Baseline Sleep disturbance: ANCOVA model was used to calculate least square (LS) mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.11695% CI: [-0.81, 7.31]ANCOVA
Comparison: Week 21 Sleep disturbance: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.84995% CI: [-3.62, 2.98]ANCOVA
Comparison: Baseline snoring: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.672895% CI: [-4.34, 6.73]ANCOVA
Comparison: Week 21 snoring: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.395495% CI: [-2.56, 6.47]ANCOVA
Comparison: Baseline Awaken Short of Breath: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.110695% CI: [-0.92, 8.98]ANCOVA
Comparison: Week 21 Awaken Short of Breath: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.360395% CI: [-6.09, 2.22]ANCOVA
Comparison: Baseline Quantity of Sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.831295% CI: [-0.3, 0.24]ANCOVA
Comparison: Week 21 Quantity of Sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.910195% CI: [-0.38, 0.42]ANCOVA
Comparison: Baseline Adequacy of Sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.334695% CI: [-7.19, 2.45]ANCOVA
Comparison: Week 21 Adequacy of Sleep: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.749195% CI: [-4.69, 3.37]ANCOVA
Comparison: Baseline Somnolence: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.116295% CI: [-0.74, 6.71]ANCOVA
Comparison: Week 21 Somnolence: ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.216395% CI: [-1.21, 5.32]ANCOVA
Comparison: Baseline Sleep Problem Index (9): ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.032195% CI: [0.3, 6.61]ANCOVA
Comparison: Week 21 Sleep Problem Index (9): ANCOVA model was used to calculate LS mean estimates of the treatment difference along with 95% CI, with main effects of treatment and country; for post-baseline, baseline was included as a covariate.p-value: 0.788995% CI: [-2.17, 2.85]ANCOVA
Secondary
Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21.
Participants who had at least 50% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 50% responders. If percent change from baseline \<= -50 then responder rate = 1 (yes) otherwise responder rate = 0 (no).
Time frame: 6 weeks Baseline, 21 weeks through End of MP for 27 weeks
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 Baseline and post Baseline primary efficacy evaluation. n=is the number of subjects that can be analyzed for each treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | All Partial Seizure (n=238, 240) | 56.3 Percentage of participants |
| Pregabalin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Complex Partial (n=161, 158) | 56.5 Percentage of participants |
| Pregabalin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Simple Partial (n=87, 88) | 55.2 Percentage of participants |
| Pregabalin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | SGTC (n=112, 114) | 50.9 Percentage of participants |
| Gabapentin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Simple Partial (n=87, 88) | 53.4 Percentage of participants |
| Gabapentin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | All Partial Seizure (n=238, 240) | 58.3 Percentage of participants |
| Gabapentin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | SGTC (n=112, 114) | 60.5 Percentage of participants |
| Gabapentin | Percentage of Participants With 50% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Complex Partial (n=161, 158) | 55.1 Percentage of participants |
Comparison: The odds ratio and its 95% CI are calculated by exponentiating the log odds ratio and 95% CI that correspond to the treatment contrast in the logistic regression model with treatment as fixed effect and Baseline term and country as covariate. All statistical tests for secondary efficacy parameters were two sided and performed at significance level of α = 0.05. The above statistical analysis applies to All Partial Seizures - FAS Population.p-value: 0.66295% CI: [0.635, 1.335]Regression, Logistic
Secondary
Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21.
Participants who had at least 75% reduction in seizure frequency from Baseline to double-blind treatment (TP + MP) were considered as 75% responders. If percent change from baseline \<= -75 then 75% responder rate = 1 (yes) otherwise responder rate = 0 (no). Total partial seizure is defined as the total number of (simple partial seizure + complex partial seizure + SGTC).
Time frame: 6 weeks Baseline, 21 weeks through End of MP for 27 weeks
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 Baseline and post Baseline primary efficacy evaluation. n=is the number of participants that can be analyzed for each treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | All Partial Seizure (n=238, 240) | 33.6 Percentage of participants |
| Pregabalin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Simple Partial (n=87, 88) | 36.8 Percentage of participants |
| Pregabalin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Complex Partial (n=161, 158) | 37.3 Percentage of participants |
| Pregabalin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | SGTC (n=112, 114) | 38.4 Percentage of participants |
| Gabapentin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | SGTC (n=112, 114) | 43.9 Percentage of participants |
| Gabapentin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | All Partial Seizure (n=238, 240) | 34.2 Percentage of participants |
| Gabapentin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Complex Partial (n=161, 158) | 36.1 Percentage of participants |
| Gabapentin | Percentage of Participants With 75% Reduction From Baseline in 28-day Seizure Rate at Week 21. | Simple Partial (n=87, 88) | 33.0 Percentage of participants |
p-value: 0.9232Fisher Exact
p-value: 0.6361Fisher Exact
p-value: 0.9075Fisher Exact
p-value: 0.4203Fisher Exact
Secondary
Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score.
MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Percentage of participants with optimal sleep are reported.
Time frame: Baseline, Week 21
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 baseline and post baseline primary efficacy evaluation. N (number of participants analyzed)=participants who were evaluable for this measure. n=number of participants evaluable at specifictime points for each arm group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score. | Baseline (n=238, 240) | 49.2 percentage of participants |
| Pregabalin | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score. | Week 21 (n=212, 210) | 51.4 percentage of participants |
| Gabapentin | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score. | Baseline (n=238, 240) | 58.8 percentage of participants |
| Gabapentin | Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score. | Week 21 (n=212, 210) | 58.6 percentage of participants |
Comparison: Baseline: Logistic regression model was used to estimate odds ratio and corresponding 95% CI of treatment difference, with treatment as fixed effect and for post-baseline assessments baseline was included as a covariate.p-value: 0.025295% CI: [0.449, 0.948]Regression, Logistic
Comparison: Week 21: Logistic regression model was used to estimate odds ratio and corresponding 95% CI of treatment difference, with treatment as fixed effect and for post-baseline assessments baseline was included as a covariate.p-value: 0.345995% CI: [0.524, 1.254]Regression, Logistic
Secondary
Percentage of Participants Without Seizures.
Seizure free for 28 days was defined as participants who have not experienced any seizure (simple partial, complex partial and SGTC) for at least 28 consecutive days from their last seizure until the end of the MP. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure.
Time frame: 6 weeks Baseline, 21 weeks through End of MP for 27 weeks
Population: FAS included all randomized participants who had received at least 1 blinded dose of study drug and had at least 1 Baseline and post Baseline primary efficacy evaluation. N (number of participants analyzed)=participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Percentage of Participants Without Seizures. | All Partial Seizure (n=189, 182) | 30.7 percentage of participants |
| Pregabalin | Percentage of Participants Without Seizures. | Simple Partial (n=74, 66) | 29.7 percentage of participants |
| Pregabalin | Percentage of Participants Without Seizures. | Complex Partial (n=126, 123) | 37.3 percentage of participants |
| Pregabalin | Percentage of Participants Without Seizures. | SGTC (n=95, 91) | 46.3 percentage of participants |
| Gabapentin | Percentage of Participants Without Seizures. | SGTC (n=95, 91) | 42.9 percentage of participants |
| Gabapentin | Percentage of Participants Without Seizures. | All Partial Seizure (n=189, 182) | 34.1 percentage of participants |
| Gabapentin | Percentage of Participants Without Seizures. | Complex Partial (n=126, 123) | 40.7 percentage of participants |
| Gabapentin | Percentage of Participants Without Seizures. | Simple Partial (n=74, 66) | 36.4 percentage of participants |
p-value: 0.5069Fisher Exact
p-value: 0.4721Fisher Exact
p-value: 0.6054Fisher Exact
p-value: 0.6603Fisher Exact
Secondary
Reduction in Proportion of the 28-day SGTC Seizure Rate Over the Total Partial Seizure Rate at Week 21.
SGTC Responder is defined as a participant who shows reduction from Baseline to double-blind phase in proportion of 28-Day SGTC Seizure Rate to 28-Day All Partial Seizure Rate.
Time frame: 6 weeks Baseline, 21 weeks through End of MP for 27 weeks
Population: SGTC population included all participants who had at least 1 SGTC seizure during either Baseline or double-blind phase. n is the number of participants analyzed for SGTC. Twenty-six participants were not included in the n because they did not have a post Baseline all partial seizure, but they were included in the analysis by seizure type.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Reduction in Proportion of the 28-day SGTC Seizure Rate Over the Total Partial Seizure Rate at Week 21. | 30.8 percentage of responders |
| Gabapentin | Reduction in Proportion of the 28-day SGTC Seizure Rate Over the Total Partial Seizure Rate at Week 21. | 39.8 percentage of responders |
p-value: 0.1881Fisher Exact