Trial Outcomes & Findings for An Open Label Study of L059 Intravenous (IV) in Japanese Epilepsy Subjects With Partial Onset Seizures (NCT NCT01407523)

Results Overview

An Adverse Event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18)

Results posted on

2013-03-07

Participant Flow

This study started to enroll subjects in July 2011 in order to end up with 4 centers in Japan. 16 subjects were treated and completed the study. All 16 subjects are included in the Safety Set.

The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form. Participant Flow and Baseline Characteristics refer to the Safety Set (SS).

Participant milestones

Participant milestones
Measure	Levetiracetam Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Overall Study STARTED	16
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Open Label Study of L059 Intravenous (IV) in Japanese Epilepsy Subjects With Partial Onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	32.9 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment Japan	16 participants n=5 Participants
Weight	68.82 kilogram STANDARD_DEVIATION 12.38 • n=5 Participants
Height	163.40 centimeter STANDARD_DEVIATION 8.95 • n=5 Participants

PRIMARY outcome

Timeframe: During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18)

Population: Safety Set (SS)

An Adverse Event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Incidence of Treatment Emergent Adverse Events During the Entire Study Period (up to 32 Days)	5 participants

PRIMARY outcome

Timeframe: During the entire Study Period from Screening (Day -14 to Day -1) over Evaluation Period (Day 1 to Day 4) to Follow-Up Period (Day 5 to Day 18)

Population: Safety Set (SS)

A Serious Adverse Event (SAE) is any untoward medical occurrence that results in death, is life-threatening, results in significant or persistent disability/incapacity, is a congenital anomaly/birth defect (including that occurring in a fetus), or is an important medical event that may jeopardize the subject or may require medical or surgical intervention.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Incidence of Treatment Emergent Serious Adverse Events During the Entire Study Period (up to 32 Days)	0 participants

SECONDARY outcome

Timeframe: Day 1

Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.

Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 1.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1	11.732 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 63.1

SECONDARY outcome

Timeframe: Day 4

Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.

Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 4.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Observed Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4	11.632 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 59.6

SECONDARY outcome

Timeframe: Day 1

Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.

Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 1. Plasma trough concentration (Ctrough) was normalized to a dose of 500 mg as follows: Dose normalized Ctrough = Ctrough/last dose \[mg\] x 500 mg.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 1	6.611 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 29.6

SECONDARY outcome

Timeframe: Day 4

Population: Pharmacokinetic Per Protocol Set (PK-PPS). This was defined as a subset of the Safety Set (SS) and consisted of subjects who had at least 1 evaluable Levetiracetam plasma concentration after intravenous administration. All 16 subjects from the SS are included in the PK-PPS.

Plasma sample for determination of Plasma trough concentration of Levetiracetam was taken prior to intravenous infusion of Levetiracetam in the morning of Day 4. Plasma trough concentration (Ctrough) was normalized to a dose of 500 mg as follows: Dose normalized Ctrough = Ctrough/last dose \[mg\] x 500 mg.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Dose Normalized Plasma Trough Concentration of Levetiracetam Prior to Intravenous (iv) Infusion on Day 4	5.492 micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 29.4

SECONDARY outcome

Timeframe: During the Evaluation Period (Day 1 to Day 4)

Population: Full Analysis Set (FAS). The FAS consisted of all subjects in the Safety Set (SS) with evaluable seizure frequency data over the Evaluation Period. All 16 subjects in the SS are included in the FAS.

Partial (Type I) seizures can be classified into one of the following three groups: Simple partial seizures, Complex partial seizures, Partial seizures evolving to secondarily generalized seizures.

Outcome measures

Outcome measures
Measure	Levetiracetam n=16 Participants Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Partial (Type 1) Seizure Frequency Per Day Over the Evaluation Period	0.38 Seizures per day Interval 0.0 to 1.0

Adverse Events

Levetiracetam

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	Levetiracetam n=16 participants at risk Twice daily intravenous (IV) infusion of Levetiracetam solution equivalent (mg-for-mg) to oral dose of Levetiracetam. Levetiracetam : * Formulation: concentrate for solution for infusion * Strength: Levetiracetam injection (100 mg/mL) will be packed in 5 mL glass vials (500 mg/5 mL) * Dosage: 1000 mg/day, 1500 mg/day, 2000 mg/day, 2500 mg/day or 3000 mg/day * Frequency: twice daily
Gastrointestinal disorders Gingivitis	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.
Gastrointestinal disorders Toothache	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.
General disorders Injection site inflammation	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.
General disorders Injection site pain	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.
General disorders Injection site swelling	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 1/16 • Number of events 1 • Adverse Events (AEs) were collected over the entire Study Period from Screening (1 to 14 days prior to the first intravenous infusion) over Evaluation Period (4 days) to the end of Follow-Up Period (1 to 14 days after the final intravenous infusion). AEs refer to Safety Set (SS). The Safety Set (SS) consisted of all subjects who started Levetiracetam intravenous (LEV IV) infusion after they had signed and dated the Informed Consent form.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1 877 822 9493 (UCB)

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60