Phase I Trail for Intramuscular Administration of Midazolam Using An Autoinjector (AAS)

This study has been completed.
Sponsor:
Information provided by:
U.S. Army Office of the Surgeon General
ClinicalTrials.gov Identifier:
NCT00534378
First received: September 20, 2007
Last updated: September 21, 2007
Last verified: September 2007
  Purpose

Purpose of the study is to determine midazolam's safety and dose-linearity when delivered intramuscularly via an autoinjector. The proposed initial treatment dosage for seizures induced by exposure to nerve agents.


Condition Intervention Phase
Seizures
Drug: Midazolam
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I, Open-Label, Single-Center Study to Evaluate the Safety and Dose Linearity of Intramuscular Administration of Midazolam Using

Resource links provided by NLM:


Further study details as provided by U.S. Army Office of the Surgeon General:

Enrollment: 39
Study Start Date: July 2006
Study Completion Date: December 2006
Arms Assigned Interventions
No Intervention: 1 Drug: Midazolam
The study drug was administered IM into the anterior thigh using the preloaded autoinjector. The autoinjectors were preloaded with midazolam 5 mg or 10 mg with a total volume of 1 or 2 mL. Healthy subjects were assigned to one of six target dosage groups (0.10, 0.18, 0.25, 0.33, 0.40, 0.49 mg/kg) and, based on their weight, received the necessary combination of fixed 5 or 10 mg doses to provide the assigned target dose.

Detailed Description:

The investigational drug product being evaluated in this study is the Midazolam Autoinjector. This system is composed of an autoinjector filled with the drug product midazolam EP. The study drug is administered IM into the anterior thigh using the preloaded autoinjector. This method of administration was selected as it is the method that will be used in later clinical trials and for the marketed product. The autoinjectors were preloaded with midazolam 5 mg or 10 mg with a total volume of 1 or 2 mL. Healthy subjects are assigned to one of six target dosage groups (0.10, 0.18, 0.25, 0.33, 0.40, 0.49 mg/kg) and, based on their weight, received the necessary combination of fixed 5 or 10 mg doses to provide the assigned target dose.

  Eligibility

Ages Eligible for Study:   18 Years to 54 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Generally health adult
  • Physically fit
  • Body Mass Index of >/- 19 and </- 26 and a body weight of 55 to 85 Kg
  • Have adequate venous access and sufficient upper leg muscle tissue
  • Have all specified laboratory values
  • Have a negative assay for HIV-1, HIV-2, HbsAg
  • If femal is of child bearing potential, she must not be pregnant or breast feeding, nor plan to become pregnant for th eduration of the study. She must have a negative blood serum pregnancy test within 21 days of treatment, and a negative urine pregnancy test prior to dosing.
  • Females of childbearing potential will use adequate contraception.
  • Willing to refrain from donating blood for 8 weeks after compeletion of the study.

Exclusion Criteria:

  • Participated in a pharmacokinetic study or any clinical study currently or within the last 30 days or donated >480mL of blood within the last 8 weeks.
  • History or presence of significant cardiovascular, hepatic, renal, hematologic, gastrointestingal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease that could potentially impact the safety of the subject or metabolism of the drug.
  • Be taking any medications to ttreat a chronic medical condition
  • Have ongoing drug abuse/dependence (including alcohol); or history of or treatment for alcohol or drug abuse
  • History of allergic or untoward reaction to any benzodiazepine or any psychotropic agent
  • Currently suffering frm acute or chronic pulmonary disease
  • Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-study screening assessment that could interfere with objectives of the study or the safety of the subject.
  • Pregnant or nursing
  • History of glaucoma
  • Positive urine test for drug abuse
  • Have an active malignancy or history of metastatic or hematologic malignancy with the exception of melanoma in situ or basal or squamous cell carcnoma of the skin Subjects with positive tests for hepatitis B, hepatitis C, syphilis, HIV-1 or HIV-2
  • Subjects whoe ECG reveals a PR interval >/- 190 msec
  • Subjects should refrain from taking any OTC preparations, herbal remedies, and/or nutritional supplement taken within 7 days prior to study drug drug administration.
  • Subjects not using medically recognized means of birth control
  • Subjects with a prior history of seizures or related conditions
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00534378

Locations
United States, Maryland
BASi Baltimore Clinical Research Unit
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
U.S. Army Office of the Surgeon General
Investigators
Principal Investigator: Thomas Holohan, MD Bioanalytical Systems, Inc.
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00534378     History of Changes
Other Study ID Numbers: 11903
Study First Received: September 20, 2007
Last Updated: September 21, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Office of the Surgeon General:
Nerve agent
Midazolam
Seizures
Severe recurrent convulsive seizures induced by nerve agent exposure

Additional relevant MeSH terms:
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Midazolam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014