Epilepsy
Conditions
Brief summary
The purpose of this study is to determine the pharmacokinetics of Diazepam Nasal Spray following a single dose in epileptic patients experiencing a seizure episode.
Interventions
DRUGDiazepam
single-dose; dosage in mg, based on patient body weight
Sponsors
Acorda Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provide signed informed consent for study participation. * General good health with no clinically significant unstable abnormalities. * Diagnosis of epilepsy.
Exclusion criteria
* Individuals receiving warfarin (Coumadin®) or dabigatran (Pradaxa®). * Use of any investigational drug within 30 days. * Blood or plasma donation within 30 days. * Not willing or unable to tolerate blood draws.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter: Maximum Measure Plasma Concentration (Cmax), | Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours | Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Cmax. The mean Cmax value was adjusted to a 20 mg dose. |
| Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) | Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours | Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Tmax. The mean Tmax value was adjusted to a 20 mg dose. |
| Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration | Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours | Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter AUC(0-12) and AUC(last). The mean estimate of AUC(0-12) was adjusted to a 20 mg dose. AUC(last) was used for the calculation of AUC for nordiazepam. AUC(0-12) values could not be estimated for nordiazepam given that nordiazepam concentrations were rising between 6 and 12 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Pre-dose to 48 hours post-dose | TEAEs refer to adverse events with start dates occurring after dosing. Treatment-Related TEAEs refer to those 'possibly' or 'probably' related to study drug. Intensity definitions: * Mild: Usually transient, required no special treatment, and did not interfere with the patient's daily activities. * Moderate: Usually caused a low degree of inconvenience or concern to the patient, and may have interfered with daily activities, but was usually ameliorated by simple therapeutic measures. * Severe: Interrupted a patient's usual daily activities, and generally required systemic drug therapy or other treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diazepam Nasal Spray Diazepam: single-dose; dosage in mg, based on patient body weight | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Diazepam Nasal Spray |
|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 12.8 |
| Body Mass Index (BMI) | 26.3 (kg/m^2) STANDARD_DEVIATION 4.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 28 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration
Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter AUC(0-12) and AUC(last). The mean estimate of AUC(0-12) was adjusted to a 20 mg dose. AUC(last) was used for the calculation of AUC for nordiazepam. AUC(0-12) values could not be estimated for nordiazepam given that nordiazepam concentrations were rising between 6 and 12 hours.
Time frame: Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours
Population: PK Population: patients who had adequate concentration-time data to permit estimation of noncompartmental PK parameters.~One patient was not included in the analysis of nordiazepam due to receiving clorazepate, which interfered with the analysis of nordiazepam from diazepam administration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diazepam Nasal Spray | Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration | AUC(0-12) | 1227 hour*nanogram/milliliter (h*ng/mL) | Standard Deviation 488 |
| Diazepam Nasal Spray | Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration | AUC(last) | NA hour*nanogram/milliliter (h*ng/mL) | — |
| Nordiazepam | Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration | AUC(0-12) | NA hour*nanogram/milliliter (h*ng/mL) | — |
| Nordiazepam | Pharmacokinetic (PK) Parameter: Area Under The Concentration Curve From Time 0 to 12 Hours (AUC(0-12)) and AUC Time to Last Measurable Plasma Concentration | AUC(last) | 192 hour*nanogram/milliliter (h*ng/mL) | Standard Deviation 148 |
Primary
Pharmacokinetic (PK) Parameter: Maximum Measure Plasma Concentration (Cmax),
Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Cmax. The mean Cmax value was adjusted to a 20 mg dose.
Time frame: Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours
Population: PK Population: patients who had adequate concentration-time data to permit estimation of noncompartmental PK parameters.~One patient was not included in the analysis of nordiazepam due to receiving clorazepate, which interfered with the analysis of nordiazepam from diazepam administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diazepam Nasal Spray | Pharmacokinetic (PK) Parameter: Maximum Measure Plasma Concentration (Cmax), | 208 nanogram/milliliter (ng/mL) | Standard Deviation 90.3 |
| Nordiazepam | Pharmacokinetic (PK) Parameter: Maximum Measure Plasma Concentration (Cmax), | 23.9 nanogram/milliliter (ng/mL) | Standard Deviation 16.5 |
Primary
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax)
Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Tmax. The mean Tmax value was adjusted to a 20 mg dose.
Time frame: Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours
Population: PK Population: patients who had adequate concentration-time data to permit estimation of noncompartmental PK parameters.~One patient was not included in the analysis of nordiazepam due to receiving clorazepate, which interfered with the analysis of nordiazepam from diazepam administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diazepam Nasal Spray | Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) | 0.98 hour (h) | Standard Deviation 0.86 |
| Nordiazepam | Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) | 11.10 hour (h) | Standard Deviation 2.14 |
Secondary
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
TEAEs refer to adverse events with start dates occurring after dosing. Treatment-Related TEAEs refer to those 'possibly' or 'probably' related to study drug. Intensity definitions: * Mild: Usually transient, required no special treatment, and did not interfere with the patient's daily activities. * Moderate: Usually caused a low degree of inconvenience or concern to the patient, and may have interfered with daily activities, but was usually ameliorated by simple therapeutic measures. * Severe: Interrupted a patient's usual daily activities, and generally required systemic drug therapy or other treatment.
Time frame: Pre-dose to 48 hours post-dose
Population: Safety Population (dosed with study drug)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Subjects with one or more TEAEs | 28 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Total number of TEAEs | 96 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Subjects with one or more Treatment-Related TEAEs | 21 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Total number of Treatment-Related TEAEs | 56 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Subjects with one or more Severe TEAEs | 1 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Total number of Severe TEAEs | 1 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Total number of Moderate TEAEs | 24 participants |
| Diazepam Nasal Spray | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | Total number of Mild TEAEs | 71 participants |