Phase I Trail for Intramuscular Administration of Midazolam Using An Autoinjector - Full Text View

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:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Seizures

Drug Information available for: Midazolam maleate Midazolam hydrochloride

U.S. FDA Resources

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.

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 (Adult)
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

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: 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


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 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

ClinicalTrials.gov processed this record on September 26, 2016

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