Phase I Trail for Intramuscular Administration of Midazolam Using An Autoinjector

NCT ID: NCT00534378

Last Updated: 2007-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2006-12-31

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.

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.

Conditions

Seizures

Keywords

Nerve agent; Midazolam; Seizures; Severe recurrent convulsive seizures induced by nerve agent exposure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: NO_INTERVENTION

Midazolam

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 54 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

U.S. Army Office of the Surgeon General

FED

Sponsor Role: lead

Principal Investigators

Thomas Holohan, MD

Role: PRINCIPAL_INVESTIGATOR

Bioanalytical Systems, Inc.

Locations

BASi Baltimore Clinical Research Unit

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

11903

Identifier Type: -

Identifier Source: org_study_id