A Study of Diazepam After Intranasal and Intravenous Administration to Healthy Volunteers

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01364558
• Collaborator: Neurelis, Inc. (Industry)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 1.9
• Patients Per Site Per Month: 12.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Diazepam; Drug: Diazepam	Phase 1

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Three-Period, Three-Treatment, Six-Sequence Randomized Crossover Study of the Bioavailability and Pharmacokinetics of Diazepam After Intranasal and Intravenous Administration to Healthy Volunteers",
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diazepam Nasal Spray Suspension Diazepam Nasal Suspension - 10 mg	Drug: Diazepam; Diazepam will be administered as a 5 mg dose given IV. The two nasal formulations will be given as a 10 mg dose.; Other Names: Brand names include: Valium, Diastat ; Drug: Diazepam; IV diazepam will be given as a 5 mg dose. The two nasal formulations will be given as 10 mg doses.; Other Names: Valium Injectable, Diastat Rectal Gel
Experimental: Diazepam Nasal Spray Solution Diazepam Nasal Spray Solution - 10 mg	Drug: Diazepam; Diazepam will be administered as a 5 mg dose given IV. The two nasal formulations will be given as a 10 mg dose.; Other Names: Brand names include: Valium, Diastat ; Drug: Diazepam; IV diazepam will be given as a 5 mg dose. The two nasal formulations will be given as 10 mg doses.; Other Names: Valium Injectable, Diastat Rectal Gel
Active Comparator: Diazepam injection Diazepam injection IV - 5 mg	Drug: Diazepam; IV diazepam will be given as a 5 mg dose. The two nasal formulations will be given as 10 mg doses.; Other Names: Valium Injectable, Diastat Rectal Gel

Outcome Measures

Primary Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Prism Clinical Research Unit	Saint Paul	Minnesota	United States	55114

Sponsors and Collaborators

• University of Minnesota
• Neurelis, Inc.

Investigators

• Principal Investigator: James Cloyd, Pharm D., University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01364558
• Other Study ID Numbers: 1012M93599
• First Posted: Jun 2, 2011
• Last Update Posted: Nov 1, 2019
• Last Verified: Oct 1, 2019

• Additional relevant MeSH terms: Epilepsy; Diazepam

Study Results

Participant Flow

Pre-assignment Detail	All 24 subjects were given each formulation with a two week wash out period.

Arm/Group Title	Diazepam Nasal Spray Suspension	Diazepam Nasal Spray Solution	Diazepam Injection
Arm/Group Description	Diazepam Nasal Spray Suspension	Diazepam Nasal Spray Solution	Diazepam injection
Period Title: Dose One
STARTED	8	8	8
COMPLETED	8	8	8
NOT COMPLETED	0	0	0
Period Title: Dose One
STARTED	8	8	8
COMPLETED	8	8	8
NOT COMPLETED	0	0	0
Period Title: Dose One
STARTED	8	8	8
COMPLETED	8	8	8
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Diazepam Nasal Spray Suspension/Spray/Injection
Arm/Group Description
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.2 (7.84)
Sex: Female, Male (Count of Participants)
Female	5 20.8%
Male	19 79.2%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diazepam Nasal Spray Suspension	Diazepam Nasal Spray Solution	Diazepam Injection
Arm/Group Description	Diazepam Nasal Spray Suspension	Diazepam Nasal Spray Solution	Diazepam injection
Measure Participants	24	24	24
Geometric Mean (90% Confidence Interval) [Percentage of Bioavailability]	69	96.82	100

Adverse Events

Arm/Group Title	Diazepam Nasal Spray Suspension		Diazepam Nasal Spray Solution		Diazepam Injection
Arm/Group Description
All Cause Mortality
	Diazepam Nasal Spray Suspension		Diazepam Nasal Spray Solution		Diazepam Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Diazepam Nasal Spray Suspension		Diazepam Nasal Spray Solution		Diazepam Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Diazepam Nasal Spray Suspension		Diazepam Nasal Spray Solution		Diazepam Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/24 (54.2%)		10/24 (41.7%)		18/24 (75%)
Gastrointestinal disorders
Gastrointestinal	2/24 (8.3%)	2	0/24 (0%)	0	1/24 (4.2%)	1
General disorders
General Disorders	0/24 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1
Infections and infestations
Infections and infestations	1/24 (4.2%)	1	0/24 (0%)	0	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue	0/24 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2
Nervous system disorders
Nervous system disorders	4/24 (16.7%)	4	3/24 (12.5%)	3	6/24 (25%)	6
Respiratory, thoracic and mediastinal disorders
Respitory, thoracic, and mediastinal disorders	5/24 (20.8%)	5	6/24 (25%)	6	6/24 (25%)	6
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	0/24 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1
Vascular disorders
Vascular disorders	1/24 (4.2%)	1	0/24 (0%)	0	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.