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

This study has been completed.
Sponsor:
Collaborator:
Neurelis
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01364558
First received: May 20, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Epilepsy
Drug: Diazepam
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
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",

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Comparison of the Absolute Bioavailability of Two Intranasal Diazepam Formulations. [ Time Frame: 2 days ] [ Designated as safety issue: No ]

    To calculate bioavailability we used the following formula:

    Area Under the Curve (Intranasal Spray)*100/Area Under the Curve (Intravenous Injection)



Enrollment: 24
Study Start Date: February 2011
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Valium Injectable, Diastat Rectal Gel

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

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01364558

Locations
United States, Minnesota
Prism Clinical Research Unit
St.Paul, Minnesota, United States, 55114
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Neurelis
Investigators
Principal Investigator: James Cloyd, Pharm D. University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01364558     History of Changes
Other Study ID Numbers: DIAZ.001.01
Study First Received: May 20, 2011
Results First Received: July 20, 2012
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Diazepam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Muscle Relaxants, Central
Neuromuscular Agents
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia

ClinicalTrials.gov processed this record on July 20, 2014