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

• ClinicalTrials.gov Identifier: NCT00534378
• Recruitment Status: Completed
• First Posted: September 24, 2007
• Last Update Posted: September 24, 2007
• Sponsor: U.S. Army Office of the Surgeon General
• Information provided by: U.S. Army Office of the Surgeon General

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Seizures	Drug: Midazolam	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: July 2006
• Actual Study Completion Date: December 2006

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 54 Years (Adult)
• Sexes Eligible for Study: All
• 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

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

• ClinicalTrials.gov Identifier: NCT00534378
• Other Study ID Numbers: 11903
• First Posted: September 24, 2007
• Last Update Posted: September 24, 2007
• Last Verified: September 2007

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; Neurologic Manifestations; Nervous System Diseases; Midazolam; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action