Trial Outcomes & Findings for A Pharmacokinetic Study of a Single-Dose of Diazepam Nasal Spray in Adult Epileptic Patients Experiencing a Seizure Episode (NCT NCT01417078)
NCT ID: NCT01417078
Last Updated: 2017-03-29
Results Overview
Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Cmax. The mean Cmax value was adjusted to a 20 mg dose.
COMPLETED
PHASE2
31 participants
Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hours
2017-03-29
Participant Flow
Participant milestones
| Measure |
Diazepam Nasal Spray
Diazepam: single-dose; dosage in mg, based on patient body weight
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Diazepam Nasal Spray
Diazepam: single-dose; dosage in mg, based on patient body weight
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Pharmacokinetic Study of a Single-Dose of Diazepam Nasal Spray in Adult Epileptic Patients Experiencing a Seizure Episode
Baseline characteristics by cohort
| Measure |
Diazepam Nasal Spray
n=31 Participants
Diazepam: single-dose; dosage in mg, based on patient body weight
|
|---|---|
|
Age, Continuous
|
35.2 years
STANDARD_DEVIATION 12.80 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
26.3 (kg/m^2)
STANDARD_DEVIATION 4.08 • n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hoursPopulation: 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.
Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Cmax. The mean Cmax value was adjusted to a 20 mg dose.
Outcome measures
| Measure |
Diazepam Nasal Spray
n=30 Participants
Diazepam: single-dose; dosage in mg, based on patient body weight
|
Nordiazepam
n=29 Participants
Diazepam was slowly converted to nordiazepam following intranasal administration
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: Maximum Measure Plasma Concentration (Cmax),
|
208 nanogram/milliliter (ng/mL)
Standard Deviation 90.3
|
23.9 nanogram/milliliter (ng/mL)
Standard Deviation 16.5
|
PRIMARY outcome
Timeframe: Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hoursPopulation: 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.
Summary of Dose-Adjusted Diazepam and Nordiazepam PK parameter Tmax. The mean Tmax value was adjusted to a 20 mg dose.
Outcome measures
| Measure |
Diazepam Nasal Spray
n=30 Participants
Diazepam: single-dose; dosage in mg, based on patient body weight
|
Nordiazepam
n=29 Participants
Diazepam was slowly converted to nordiazepam following intranasal administration
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax)
|
0.98 hour (h)
Standard Deviation 0.86
|
11.10 hour (h)
Standard Deviation 2.14
|
PRIMARY outcome
Timeframe: Pre-dose, 10, 15, 30, and 45 mins, and 1, 1.5, 2, 4, 6, 9,and 12 hoursPopulation: 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.
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.
Outcome measures
| Measure |
Diazepam Nasal Spray
n=30 Participants
Diazepam: single-dose; dosage in mg, based on patient body weight
|
Nordiazepam
n=29 Participants
Diazepam was slowly converted to nordiazepam following intranasal administration
|
|---|---|---|
|
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
|
NA hour*nanogram/milliliter (h*ng/mL)
Standard Deviation NA
AUC(0-12) values could not be estimated for nordiazepam given that nordiazepam concentrations were rising between 6 and 12 hours
|
|
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)
Standard Deviation NA
AUC(last) was used for the calculation of AUC for nordiazepam.
|
192 hour*nanogram/milliliter (h*ng/mL)
Standard Deviation 148
|
SECONDARY outcome
Timeframe: Pre-dose to 48 hours post-dosePopulation: Safety Population (dosed with study drug)
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.
Outcome measures
| Measure |
Diazepam Nasal Spray
n=31 Participants
Diazepam: single-dose; dosage in mg, based on patient body weight
|
Nordiazepam
Diazepam was slowly converted to nordiazepam following intranasal administration
|
|---|---|---|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Subjects with one or more TEAEs
|
28 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Total number of TEAEs
|
96 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Subjects with one or more Treatment-Related TEAEs
|
21 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Total number of Treatment-Related TEAEs
|
56 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Subjects with one or more Severe TEAEs
|
1 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Total number of Severe TEAEs
|
1 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Total number of Moderate TEAEs
|
24 participants
|
—
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Total number of Mild TEAEs
|
71 participants
|
—
|
Adverse Events
Diazepam Nasal Spray
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Diazepam Nasal Spray
n=31 participants at risk
Diazepam: single-dose; dosage in mg, based on patient body weight
|
|---|---|
|
Nervous system disorders
Headache
|
51.6%
16/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Nervous system disorders
Dysgeusia
|
25.8%
8/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Nervous system disorders
Somnolence
|
16.1%
5/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Nervous system disorders
Dizziness
|
9.7%
3/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
22.6%
7/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
16.1%
5/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.9%
4/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
|
12.9%
4/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
9.7%
3/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Parosmia
|
9.7%
3/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.5%
2/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
6.5%
2/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus discomfort
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Gastrointestinal disorders
Nausea
|
16.1%
5/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Eye disorders
Lacrimation increased
|
16.1%
5/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
General disorders
Fatigue
|
6.5%
2/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
General disorders
Catheter site pain
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
General disorders
Feeling hot
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
General disorders
Peripheral coldness
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Injury, poisoning and procedural complications
Tongue injury
|
12.9%
4/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.5%
2/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Investigations
Blood pressure increased
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
|
Renal and urinary disorders
Urinary retention
|
3.2%
1/31 • Pre-dose to 48 hours post-dose
TEAEs refer to AEs with start date and times occuring after dosing.
|
Additional Information
Executive Medical Director - Clinical Development & Medical Affairs
Acorda Therapeutics, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has right to review at least forty-five (45) days prior to the date of submission for publication or of public disclosure. Multi-center trials; publication shall be delayed until a publication of the multi-center results or until twelve (12) months have elapsed since the completion of the study, whichever occurs first.
- Publication restrictions are in place
Restriction type: OTHER