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Keywords:

  • Epilepsy;
  • Partial-onset seizures;
  • Lacosamide;
  • Antiepileptic drugs;
  • Intravenous

Summary

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Purpose: This multicenter, double-blind, double-dummy, randomized, inpatient trial evaluated the safety, tolerability, and pharmacokinetics of intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures.

Methods: Patients were enrolled from an ongoing open-label extension trial of oral lacosamide and randomized (2:1) to either intravenous lacosamide and oral placebo or intravenous placebo and oral lacosamide. During the 2-day inpatient treatment period, patients received twice-daily doses of lacosamide equivalent to their current daily dose of oral lacosamide. The first 30 patients enrolled received infusions with 60-min durations and the next 30 received infusions with 30-min durations.

Results: Of 60 patients randomized, 59 completed the trial. Treatment-emergent adverse events (AEs) were reported by 16 patients and included dizziness, headache, back pain, somnolence, and injection site pain. The tolerability profile of intravenous lacosamide was consistent with that of oral lacosamide. All AEs were considered mild or moderate in intensity, and no serious AEs or AEs leading to withdrawal were reported.

Conclusions: Intravenous lacosamide, administered as 60- or 30-min twice-daily infusions, showed a similar safety and tolerability profile to oral lacosamide when used as replacement therapy. Results from this trial support further investigation of intravenous lacosamide at shorter infusion durations.


Introduction

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Lacosamide, a new chemical entity being developed as an oral tablet (Bialer et al., 2004) for the treatment of epilepsy and diabetic neuropathic pain, is also being developed in an intravenous formulation. Preclinical studies have demonstrated that lacosamide protects against seizures in various anticonvulsant animal models as well as in models of status epilepticus (Bialer et al., 2002). In a recently completed randomized controlled trial, adjunctive oral lacosamide was shown to significantly reduce seizure frequency in patients with uncontrolled partial-onset seizures (Ben-Menachem et al., 2007).

Studies in healthy volunteers have shown that oral lacosamide has a high bioavailability (approximately 100%) that is not affected by food (Bialer et al., 2001; Cawello et al., 2004). The plasma half-life of oral lacosamide is approximately 13 h following a single dose or chronic twice-daily dosing (Bialer et al., 2004). There is a linear relationship between oral lacosamide plasma concentration and dose (100–800 mg/day) (Horstmann et al., 2002). Lacosamide is minimally bound to plasma proteins (<15%), and in clinical studies, oral lacosamide has shown no effect on the plasma concentrations of concomitantly administered antiepileptic drugs (AEDs) (Hovinga, 2003; Jatuzis et al., 2005; Kropeit et al., 2005).

When patients with partial-onset seizures are hospitalized, undergoing surgical procedures, experiencing difficulty swallowing, or suffering from acute gastrointestinal disorders, oral administration of their AED may not be feasible, temporarily. For continued seizure control, an alternative route of administration for the AED becomes necessary. Maintaining patients on their current AED using an intravenous formulation avoids the risk of seizure exacerbation and also avoids the risk of poor tolerability associated with switching to a different AED that can be administered parenterally (Wheless and Venkataraman, 1999).

The intravenous formulation of lacosamide is a 10 mg/mL isotonic solution (pH of 3.5–5) that is stable at room temperature and can be administered without dilution (Biton et al., 2005). Pharmacokinetic data from phase 1 trials of intravenous lacosamide demonstrated bioequivalence (Cmax, AUC) between 200 mg of lacosamide administered as oral tablets and 200 mg of intravenous lacosamide administered at infusion durations of 60 and 30 min (Kropeit et al., 2004).

The primary objective of this inpatient trial was to evaluate the safety and tolerability of intravenous lacosamide as replacement therapy for oral lacosamide (200 mg/day to 600 mg/day) in patients with partial-onset seizures with or without secondary generalization. The secondary objective was to assess the pharmacokinetic profile of intravenous lacosamide. This was the first intravenous lacosamide trial in patients with epilepsy.

Methods

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

The trial was conducted between March and August 2004 at five sites in the United States and two sites in Lithuania. The trial was conducted in accordance with the Declaration of Helsinki, European Directive 2001/83/EC, the U.S. Code of Federal Regulations Part 21, and the International Conference on Harmonization Good Clinical Practice guidelines. The trial protocol, amendments, and informed consent were reviewed by national regulatory authorities in each country and relevant ethics committees or Institutional Review Boards for each site. Before trial participation, all patients gave written informed consent.

Trial population

Patients already enrolled in an ongoing open-label extension trial and receiving oral lacosamide for at least 8 weeks for the treatment of partial-onset seizures were screened for enrollment in this trial. These patients had been on a stable dose of lacosamide (200–600 mg/day) and concomitant AEDs as well as a stable vagus nerve stimulation (VNS) setting, if applicable, for the previous 2 weeks. In addition, eligible patients had to have normal platelet counts and be acceptable candidates for venipuncture and intravenous infusion.

The same exclusion criteria used for the open-label trial of oral lacosamide were applied to this double-blind trial of intravenous lacosamide. Women who were pregnant, breast-feeding, or of childbearing potential and not practicing birth control, as well as any patients who had donated blood within 3 months of screening or had participated in an investigational trial (other than the oral lacosamide open-label extension trial) within the previous 2 months were excluded. Patients were also excluded if they had a major protocol violation during the open-label trial, met the withdrawal criteria for the oral lacosamide open-label extension trial, or were experiencing an ongoing serious adverse event (AE). Also excluded were patients with sitting diastolic blood pressure outside the range of 50–105 mmHg, or resting pulse outside the range of 50–110 bpm; history of severe anaphylactic reaction or serious blood dyscrasias; history of status epilepticus; progressive structural lesion in the central nervous system (CNS) or progressive encephalopathy; any other clinically significant disease or surgical condition; recent chronic consumption of non-AED medications influencing the CNS, including sedative antihistamines, anxiolytics, hypnotics, or tranquilizers; or a confirmed clinically significant electrocardiogram (ECG) abnormality.

Trial design

This multicenter, double-blind, double-dummy, randomized, inpatient trial consisted of a screening period, treatment period, and end-of-treatment assessment period. During the 1-day screening period, patients received a single infusion of intravenous placebo in a single-blind manner as well as their twice-daily dose of oral lacosamide. During the 2-day treatment period, patients received blinded trial medication twice daily at the same dose that they had received in the oral lacosamide open-label extension trial, ranging from 200 to 600 mg/day. End-of-treatment assessments were performed the day after the treatment period was completed. After completion of this trial, patients resumed participation in the oral lacosamide open-label extension trial at their usual dose.

Eligible patients were enrolled in the current trial and randomized in a 2:1 ratio to one of the two treatment groups: (1) intravenous lacosamide and placebo tablets twice daily or (2) intravenous placebo and oral lacosamide tablets twice daily. The first 30 patients received trial medication infusion over a duration of 60 min; the next 30 patients received trial medication infusion over a duration of 30 min. Safety data for the 60-min infusion duration group were evaluated by a data-monitoring committee before enrollment into the 30-min infusion duration group began.

To ensure blinding, vials, tablets, and packaging for all trial medication were identical in appearance. Patients randomized to intravenous placebo and oral lacosamide received a colorless normal saline solution, while patients randomized to intravenous lacosamide and oral placebo received colorless lacosamide solution for infusion (10 mg/mL) at a dose equivalent to their oral dose of lacosamide in the open-label trial. Intravenous doses of lacosamide or placebo were administered undiluted by syringe infusion pump into a peripheral intravenous catheter.

Safety assessments

Safety evaluations included assessment of AEs, physical and neurological examination findings, vital signs, standard 12-lead electrocardiogram (ECGs) readings, clinical laboratory values (hematology, chemistry, and urinalysis), and seizure counts.

AEs, reported spontaneously by the patient or observed by the investigator, were characterized as to seriousness, intensity, relationship to trial medication, and outcome. Physical and neurological examinations were performed at screening and on the third day of the trial. A 12-lead ECG was performed at screening, up to 1 h before the morning dose of trial medication on each day of the trial, and at predefined intervals during and after both the morning and evening doses of trial medication on the first 2 days of the trial. All recorded ECGs were centrally read. Vital signs were measured on each day of trial participation, in conjunction with ECG recordings. Blood and urine samples for hematology, chemistry, and urinalysis testing were collected on the first and third days of the trial. During this trial, patients continued to record their seizure counts in daily diaries.

Pharmacokinetic analysis

Blood samples were collected every day of the trial—after ECG and vital sign assessments and within 20 min before the start of the morning infusion of trial medication. In addition, on the second day, blood samples for analysis of lacosamide plasma concentrations were collected 0.5, 1, 1.5, 2, 4, 8, and 12 h after the start of the morning infusion of trial medication. The 1-h sample for the 60-min infusion group and the 0.5-h sample for the 30-min infusion group were collected at the time of infusion completion. Samples collected on both days were also analyzed for concomitant AED plasma concentration. Blood samples were collected from the arm opposite the site of the intravenous infusion of trial medication.

Pharmacokinetic parameters calculated for lacosamide included maximum plasma concentration (Cmax), minimum plasma concentration (Cmin), and area under the plasma concentration versus time curve from time 0 to 12 h after administration of trial medication (AUC(0–12)). In addition, AUC(0–12), Cmax, and Cmin of lacosamide were normalized with respect to dose and body weight (resulting in AUC(0–12), norm, Cmax, norm, and Cmin, norm). The quantification of lacosamide was performed using a validated liquid chromatography/mass spectrometry (LC/MS) method in the concentration range of 0.02 to 12 μg/mL.

Statistical analysis

Primary safety analyses were conducted on all patients who received at least one dose of trial medication. Descriptive statistics were computed by trial day and time point for other key variables as appropriate, for both continuous and categorical variables. For continuous variables, descriptive statistics included the number of patients with no missing data, mean, standard deviation (SD), median, minimum, and maximum values. For categorical variables, the number and percentage of patients within each category were determined. The denominators for percentages were based on the number of patients with data appropriate for summary purposes. No formal sample size calculations were performed; thus, no statistical testing was appropriate. A planned sample size of 30 patients for each infusion duration, 20 receiving intravenous lacosamide and oral placebo, and 10 receiving intravenous placebo and oral lacosamide, was deemed adequate to meet the trial objectives.

Treatment-emergent adverse events (TEAEs) were defined as AEs that had an onset after initiation of the first intravenous infusion during the treatment period. The incidence of TEAEs was summarized by treatment group and infusion duration for all TEAEs. Electrocardiogram, vital sign, and clinical laboratory changes were assessed with respect to baseline from the time of entry into the current trial (before treatment with intravenous lacosamide).

Seizure counts during the trial were compared with baseline seizure data (with baseline defined as the previous 8 weeks of the open-label lacosamide trial before entry in the current trial) for all patients with at least 1 day of seizure diary data recorded during the 2-day treatment period of this trial. Daily seizure frequency across baseline and treatment period days was evaluated by review of individual patient data for each group.

Pharmacokinetic analyses were performed on patients with valid plasma concentration data. Descriptive statistics were calculated for AUC(0–12), Cmax, and Cmin, which were derived from day 2 concentration data. The AUC(0–12), Cmax, and Cmin were normalized with respect to dose and body weight such that the normalized parameter was equal to (parameter × body weight [kg]/dose [mg]). For AUC(0–12), Cmax, and Cmin, log-scale least-square means (LS means) and log-scale differences were exponentiated to obtain the geometric LS means and ratio estimates.

Statistical analyses were performed using the SAS software version 8.2 (SAS Institute, Inc., Cary, NC, U.S.A.).

Results

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

Demographics

All 60 of the patients screened were enrolled in the trial, received at least one dose of trial medication, and underwent baseline and postbaseline assessments (Fig. 1). A total of 59 patients received four intravenous doses of lacosamide or placebo and completed the trial; one patient discontinued because of inability to gain vascular access for pharmacokinetic sampling. No patients withdrew from the trial because of AEs.

image

Figure 1. Patient disposition (A) One patient discontinued because of lack of vascular access on day 2.

Download figure to PowerPoint

Baseline demographic characteristics for the enrolled patients were comparable between treatment groups. The mean age was 41.7 years (SD 9.80) and the age range was 19–61 years (Table 1). Most patients (88%) were white, and approximately half (58%) were female.

Table 1.  Baseline patient characteristics
Characteristic60-min infusion30-min infusionAll patients (n = 60)
Oral lacosamide with IV placebo (n = 10)IV lacosamide with oral placebo (n = 20)Oral lacosamide with IV placebo (n = 11)IV lacosamide with oral placebo (n = 19)
  1. IV, intravenous; kg, kilogram; SD, standard deviation; yr, year.

Age, yr 
 Mean ± SD40.8 ± 9.3143.7 ± 11.9543.6 ± 8.1438.9 ± 8.2641.7 ± 9.80
 Range27–5919–6123–5222–6119–61
Weight, kg 
 Mean ± SD84.65 ± 14.7386.34 ± 26.4779.29 ± 22.1872.10 ± 21.2280.26 ± 22.74
 Range52.6–108.058.1–148.348.1–110.246.1–133.446.1 – 148.3
Sex, n (%) 
 Male5 (50)9 (45)4 (36)7 (37)25 (42)
 Female5 (50)11 (55)7 (64)12 (63)35 (58)
Race, n (%) 
 Caucasian9 (90)17 (85)9 (82)18 (95)53 (88)
 Black1 (10)2 (10)2 (18)1 (5)6 (10)
 Asian0 (0)1 (5)0 (0)0 (0)1 (2)
 Other0 (0)0 (0)0 (0)0 (0)0 (0)

Among the 30 patients in the 60-min infusion duration group, 13 (43%) were taking one concomitant AED, and 17 (57%) were taking two concomitant AEDs. Among the 30 patients in the 30-min infusion duration group, 7 (23%) were taking one AED and 23 (77%) were taking two concomitant AEDs.

Safety

A total of 39 patients received intravenous lacosamide, 20 at an infusion duration of 60 min and 19 at an infusion duration of 30 min (Table 2). Thirty of the 39 patients (77%) receiving intravenous lacosamide were taking lacosamide at a dose of 400–600 mg/day.

Table 2.  Summary of patient exposure
Lacosamide dose60-min infusion30-min infusion
Oral lacosamide with IV placebo (n = 10) n (%)IV lacosamide with oral placebo (n = 20) n (%)Oral lacosamide with IV placebo (n = 11) n (%)IV lacosamide with oral placebo (n = 19) n (%)
  1. a1 patient discontinued prematurely (withdrew consent) for lack of vascular access after receiving 2 out of 4 doses of intravenous lacosamide. All other patients received 4 doses of both oral and intravenous trial medication. bid, twice daily; IV, intravenous.

200 mg/day (100 mg bid)1 (10)1 (5)1 (9)3 (16)
300 mg/day (150 mg bid)1 (10)2 (10)3 (27)3 (16)
400 mg/day (200 mg bid)1 (10)2 (10)2 (18)9 (47)
500 mg/day (250 mg bid)3 (30)7 (35)2 (18)3 (16)
600 mg/day (300 mg bid)4 (40)8a (40)3 (27)1 (5)

Of the 60 patients enrolled, 16 (27%) experienced at least one TEAE during this trial (Table 3). The frequency of patients experiencing at least one TEAE was higher in patients taking at least 400 mg/day (13 of 45, 29%) than in the smaller group of patients taking less than 400 mg/day intravenous or oral lacosamide (3 of 14, 21%). The incidences of TEAEs reported by at least two patients were higher in the intravenous lacosamide groups than in the oral lacosamide groups (Table 3). Events reported by at least two patients in the intravenous lacosamide groups included dizziness (three patients) as well as back pain, headache, injection site pain, and somnolence (two patients each). All events were mild or moderate in intensity. None of the TEAEs were reported to be serious by the investigators and none resulted in discontinuation of intravenous lacosamide. Both of the patients reporting injection site pain were in the 30-min lacosamide infusion group; however, these AE reports occurred during only one out of four 30-min infusions, were mild to moderate in intensity, were not reported to have interfered with the administration of trial medication, and resolved the same day or on the following day. The three AEs of dizziness were all mild in intensity; two of these AEs were considered possibly related to trial medication and the other was not. For all three patients, the dizziness resolved in 1–3 days with no change in trial medication. The two AE reports of back pain were mild or moderate in intensity, both were reported to be unrelated to trial medication, one resolved the same day, and one patient had a history of back pain that was ongoing at trial entry.

Table 3.  Treatment-emergent adverse events
Adverse eventa60-min infusion30-min infusion
Oral lacosamide with IV placebo (n = 10)IV lacosamide with oral placebo (n = 20)Oral lacosamide with IV placebo (n = 11)IV lacosamide with oral placebo (n = 19)
  1. aPatients reporting the same adverse event more than once are counted once per adverse event. Individual types of adverse events that were reported for 2 or more patients in any treatment group or infusion duration are displayed.IV, intravenous; TEAE, treatment-emergent adverse event.

Any TEAE, n (%) 3 (30)5 (25) 2 (18)6 (32)
Injection site pain, n (%)0 (0)0 (0) 0 (0)2 (11)
Dizziness, n (%)0 (0)1 (5) 0 (0)2 (11)
Headache, n (%)0 (0)2 (10)1 (9)0 (0) 
Back pain, n (%)0 (0)2 (10)0 (0)0 (0) 
Somnolence, n (%)0 (0)0 (0) 0 (0)2 (11)

Assessment of heart rate as well as systolic and diastolic blood pressure did not reveal any changes of clinical concern. Outliers for these variables were infrequent and no patterns were observed for treatment groups or infusion durations. Across all treatment groups and infusion durations, there were no mean changes from baseline in clinical chemistry, hematology, and urinalysis parameters that were of clinical concern.

Evaluation of ECG data generally showed consistent findings during or following each of the four administrations of lacosamide. There were minimal changes in the mean QTcF interval (QT corrected–Fridericia method) and QRS duration. No patient had a QTcF interval greater than or equal to 500 ms or an increase in QTcF interval of greater than or equal to 60 ms compared to the day 1 baseline value. One patient taking oral lacosamide experienced an 18-ms increase in QRS duration that was reported as an AE of mild intensity. Lacosamide administration was associated with a small increase in mean PR interval in both the intravenous and oral lacosamide groups. For the day 2 morning administration, the mean increase (±SD) in PR interval was 9.5 (±10.3) ms and 5.7 (±15.10) ms at the end of the 30- and 60-min intravenous lacosamide infusions, respectively. Two hours following the start of infusion, the mean increases in the intravenous lacosamide groups declined to 2.8 (±10.82) ms and 1.2 (±13.49) ms, respectively. Two hours following the administration of oral lacosamide and intravenous placebo to the control groups, the mean PR interval increase was 6.5 (±12.96) and 0.4 (±7.93) ms for the 30- and 60-min infusion durations, respectively.

Compared with seizure counts during the previous 8 weeks in the open-label extension trial, review of individual data showed that the daily number of seizures experienced by patients in this trial remained stable. Of the 60 patients enrolled, 48 reported no seizures during the trial. Of the 12 patients who reported seizures during the trial, 6 reported one or more seizures during the treatment period; 1 received intravenous lacosamide as a 60-min infusion, 2 received intravenous lacosamide as a 30-min infusion, and 3 received oral lacosamide. For all patients, the number of seizures reported during the treatment period did not exceed the number of seizures reported on the day with the maximum number of seizures during the previous 8 weeks. In general, the pattern and daily frequency of seizures during the treatment period was consistent with the pattern and daily frequency of seizures prior to trial entry for any patient who had a seizure during the treatment period.

Pharmacokinetics

Pharmacokinetic parameters AUC(0–12), Cmax, and Cmin were derived from concentration data for day 2. For body-weight- and dose-normalized AUC(0–12), Cmax, and Cmin, treatment ratios were calculated to compare the pharmacokinetics of lacosamide after intravenous infusion over 60 and 30 min with the pharmacokinetics of lacosamide after oral treatment within each infusion duration group, as shown in Table 4. Ratios for intravenous to oral lacosamide for AUC(0−-12)norm were near 100%. Thus, the bioavailability of lacosamide after intravenous treatment for both the 60− and 30−min infusions was comparable to that after oral treatment. Values of Cmax,norm were slightly elevated after intravenous treatment compared to oral treatment. This is reflected in ratios for intravenous to oral above 110% for Cmax,norm. Values of Cmin,norm were slightly decreased after intravenous treatment, which is reflected in ratios for intravenous to oral of approximately 90%.

Table 4.  Pharmacokinetic parameters on day 2
Parameter(60-min infusion)(30-min infusion)
Oral lacosamide with IV placebo (mean ± SD)IV lacosamide with oral placebo (mean ± SD)Oral lacosamide with IV placebo (mean ± SD)IV lacosamide with oral placebo (mean ± SD)
  1. AUC(0–12)norm, area under the concentration curve from 0 to 12 h after administration of trial medication normalized by body weight and dose; Cmax,norm, maximum plasma concentration normalized by body weight and dose; Cmin,norm, minimum plasma concentration normalized by body weight and dose; IV, intravenous; SD, standard deviation.

AUC(0–12)norm (μg/mL*h*kg/mg)40.18 ± 15.9038.60 ± 11.2336.91 ± 18.5933.55 ± 10.95
 (n = 10) (n = 17) (n = 11) (n = 15)
Cmax,norm (μg/mL*kg/mg)4.69 ± 1.785.01 ± 1.254.03 ± 1.734.56 ± 1.16
 (n = 10) (n = 17) (n = 11) (n = 15)
Cmin,norm (μg/mL*kg/mg)2.32 ± 1.192.09 ± 0.912.20 ± 1.381.86 ± 0.77
 (n = 10) (n = 17) (n = 11) (n = 15)

In this trial, the sample sizes for any of the individual concomitant AEDs were too small (<6 patients per group) to make an evaluation regarding any effect of intravenous lacosamide on the plasma concentrations of any of these drugs.

Discussion

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

This trial supports the safety of intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures, with or without secondary generalization. Intravenous lacosamide at doses of 200–600 mg/day (100–300 mg bid, respectively) administered at an infusion duration of 60 min demonstrated a similar safety and tolerability profile to oral lacosamide. At doses of 200 and 400 mg/day, lacosamide administered at infusion duration of 30 min demonstrated similar safety and tolerability compared to oral lacosamide.

Results from this trial support the safety of intravenous lacosamide as a short-term (up to 2 days) replacement therapy for oral lacosamide in patients with partial-onset seizures. The safety and tolerability profile for intravenous lacosamide was similar to oral lacosamide based on analyses of AEs, ECGs, vital signs, and seizure counts. Few AEs were reported after intravenous infusion of lacosamide over 2 days. The nature and incidence rate of the reported AEs were consistent with those reported while these same patients were taking oral lacosamide in the open-label extension trial, as well as consistent with the AEs reported after oral administration of lacosamide in phase 2 and 3 trials (Sachdeo et al., 2003; Ben-Menachem et al., 2005). Mean ECG values (PR, QRS, QT, and QTc) and vital signs were comparable across treatment groups and infusion durations. No change in the general pattern of seizures was noted with the use of intravenous lacosamide.

Even though intravenous and oral lacosamide were studied in a parallel design involving separate groups, bioavailability of lacosamide after 60- and 30-min infusions was comparable with oral administration with a slightly increased Cmax value after intravenous infusion.

Switching patients between oral and intravenous formulations of their current AED for surgery, hospitalization, swallowing difficulty, or gastrointestinal complications reduces the likelihood of seizure exacerbation from withholding their AED. It also avoids unexpected side effects from using an alternative AED (Wheless and Venkataraman, 1999). Because the bioavailability and tolerability of oral and intravenous lacosamide are comparable, lacosamide may offer the advantage of direct conversion from oral to intravenous administration, and vice versa, without the need for titration or dose adjustment. Because of its solubility, therapeutic dosages of intravenous lacosamide (10 mg/mL) can easily be administered with small volumes without dilution.

Based on the limited exposure to higher doses in this trial, additional research is needed to determine the safety and tolerability profile of the 500- and 600-mg/day doses of lacosamide with a 30-min infusion duration. In addition, a clearer understanding of the full safety profile of the intravenous formulation of lacosamide will require additional patient exposures and examination of the potential effects of even shorter infusion durations.

In summary, results from this trial support the safety and utility of intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures.

Acknowledgments

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References

The authors wish to acknowledge the contributions made by all of the members of the SP616 Study Group who have contributed materially to the contents of this manuscript by their participation in taking care of patients according to the approved protocol and contributing to the total data generated for this trial: A. Arain, Nashville, TN, U.S.A.; V. Biton, Little Rock, AR; N. Fountain, Charlottesville, VA, U.S.A.; G. Krauss, Baltimore, MD, U.S.A.; R. Mameniskiene, Vilnius, Lithuania; W. Rosenfeld, St. Louis, MO, U.S.A.; N. Vaiciene, Kaunas, Lithuania.

SCHWARZ PHARMA AG, Monheim, Germany, provided the trial supplies and SCHWARZ BIOSCIENCES, Inc., Research Triangle Park, NC, U.S.A., sponsored and funded the trial.

SCHWARZ BIOSCIENCES, Inc., provided trial management and site monitoring, and collected and managed patient data at all sites except 2. For the sites in Vilnius and Kaunas, Lithuania, site monitoring was performed by IFE Baltic (Vilnius, Lithuania). StatWorks, Inc. (Carrboro, NC, U.S.A.) provided SAS tables, figures, and listings from patient data. Central laboratory testing was performed by Quintiles Laboratories (Smyrna, GA, U.S.A.) for the sites in the United States, and by Quintiles Laboratories Europe (West Lothian, Scotland, U.K.) for sites in Lithuania. Central electrocardiographic services for all sites were provided by Biomedical Systems (St. Louis, MO, U.S.A., and Brussels, Belgium).

Deana G. Betterton-Lewis provided medical writing services on behalf of SCHWARZ BIOSCIENCES, Inc., Research Triangle Park, NC, U.S.A.

References

  1. Top of page
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
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