Epilepsy
Conditions
Brief summary
The purpose of this clinical research study is to assess the bioavailability and pharmacokinetics of two formulations of diazepam after intranasal (nasal spray) and injectable diazepam after intravenous (I.V.) administration
Detailed description
Diazepam is a medication that is used for the treatment of seizures. It was approved by the Food and Drug Administration (FDA) for use in the United States and is currently sold as Valium® tablets, Diazepam Injection and Diastat® rectal gel. This study will evaluate two intranasal (nasal spray) formulations of diazepam which will be supplied by Neurelis, Inc. The purpose of this clinical research study is to assess the bioavailability and pharmacokinetics of two formulations of diazepam after intranasal (nasal spray) and injectable diazepam after intravenous (I.V.) administration. Bioavailability is a measure of how much drug is absorbed and present in the blood. Pharmacokinetics means to study the way a drug enters and leaves the blood and tissues over time
Interventions
DRUGDiazepam
Diazepam will be administered as a 5 mg dose given IV. The two nasal formulations will be given as a 10 mg dose.
Sponsors
Neurelis, Inc.
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and female subjects between the ages of 18 and 45 years (inclusive). 2. Written informed consent to participate in the study. 3. Body mass index (BMI) between 19 and 30 kg/m², inclusive. 4. Female subjects of childbearing potential, defined as not surgically sterile or at least two years (2) postmenopausal, must agree to use one of the following forms of contraception from three (3) months prior through 12 days following the last dose of study drug: hormonal (oral, transdermal, implant, or injection), barrier (condom, diaphragm with spermicide), IUD, or vasectomized partner (six months minimum). Subjects must have used the same method for at least three (3) months prior to starting the study. 5. No clinically significant abnormal findings in the medical history, on the physical examination, electrocardiogram (ECG), or clinical laboratory results during Screening. 6. Subjects must agree to return to the study site for all study visits, including the three (3) confinement periods, and must be willing to comply with all required study procedures.
Exclusion criteria
1. A history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, severe seasonal or non seasonal allergies, nasal polyps or any nasal passage abnormality that could interfere with nasal spray administration, or any other condition which, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results. 2. A history of allergic or adverse responses to diazepam or any comparable or similar product. 3. Subjects who (for whatever reason) have been on an abnormal diet (such as one that severely restricts specific basic food groups \[e.g., ketogenic diet\], limits calories \[e.g., fast\], and/or requires the use of daily supplements as a substitute for the foods typically eaten at mealtimes), during the four (4) weeks preceding the study. 4. Subjects who donated blood or plasma within 30 days of the first dose of study drug. 5. Participation in a clinical trial within 30 days prior to the first dose of study drug. Participation in an observational (non interventional) study is not excluded as long as there are no scheduling conflicts with this study. 6. Inadequate or difficult venous access that may jeopardize the quality or timing of the PK samples. 7. Use of any over the counter (OTC) medication, including vitamins, within seven (7) days prior to the first dose of the study drug or during the study, unless approved by the Principal Investigator. 8. Use of any prescription medication, including benzodiazepines, within 14 days prior to the first dose of study drug or during the study, with the exception of hormonal contraceptives for women of childbearing potential, unless approved by the Principal Investigator. 9. Treatment with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study drug or during the study. 10. Smoking or use of tobacco products within six (6) months prior to the first dose of study drug or during the study. 11. Female subjects who are trying to conceive, are pregnant, or are lactating. 12. Positive serum pregnancy test at Screening or urine pregnancy test prior to each administration of study drug for all women, regardless of childbearing potential. 13. Positive blood screen for HIV, Hepatitis B surface antigen (HbSAg), or Hepatitis C, or a positive urine screen for alcohol, drugs of abuse, or cotinine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations. | 2 days | To calculate bioavailability we used the following formula: Area Under the Curve (Intranasal Spray)\*100/Area Under the Curve (Intravenous Injection) |
Countries
United States
Participant flow
Pre-assignment details
All 24 subjects were given each formulation with a two week wash out period.
Participants by arm
| Arm | Count |
|---|---|
| Diazepam Nasal Spray Suspension/Spray/Injection | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Diazepam Nasal Spray Suspension/Spray/Injection |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 32.2 years STANDARD_DEVIATION 7.84 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 24 | 10 / 24 | 18 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations.
To calculate bioavailability we used the following formula: Area Under the Curve (Intranasal Spray)\*100/Area Under the Curve (Intravenous Injection)
Time frame: 2 days
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Diazepam Nasal Spray Suspension | Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations. | 69 Percentage of Bioavailability |
| Diazepam Nasal Spray Solution | Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations. | 96.82 Percentage of Bioavailability |
| Diazepam Injection | Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations. | 100 Percentage of Bioavailability |