Pilot study to investigate the pharmacokinetics and tolerability of midazolam nose spray

ISRCTN ISRCTN79059168
DOI https://doi.org/10.1186/ISRCTN79059168
Secondary identifying numbers N/A
Submission date
11/05/2011
Registration date
18/05/2011
Last edited
30/10/2015
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Epilepsy is a condition that affects the brain and causes repeated seizures. Before a drug can be given to people with epilepsy, it is necessary to know how the drug behaves in the human body. One of the first steps is to give the drug to healthy volunteers and analyze blood samples. After analyzing we can describes how the body affects a drug, including absorption (entering the blood circulation), distribution, metabolism and elimination of the drug - this is called pharmacokinetics. Doctors usually treat epileptic seizures with diazepam given through the anus, but this kind of application is not patient friendly and difficult to administer by bystanders. To find another drug to stop epileptic seizures, we need to find other drugs and ways to deliver them. Midazolam nose spray has been developed for this goal. The aim of this study is to find out about the absorption, distribution, metabolism and elimination of midazolam when administered as a nose spray compared to midazolam administered intravenously (into a vein) in healthy volunteers.

Who can participate?
Healthy volunteers aged 18-65.

What does the study involve?
Participants are randomly allocated to one of two groups. Participants in group 1 are treated with the midazolam nose spray, then after at least five days they are treated with intravenous midazolam.
Participants in group 2 receive the same treatments in the reverse order. In both groups blood samples are taken before administration and at regular intervals up to 240 minutes after dosing. During these 240 minutes participants inform the researcher of any adverse effects and indicate the degree of drowsiness and burning feeling in the nose.

What are the possible benefits and risks of participating?
All treatments have side effects. The most common side effect of midazolam nose spray is drowsiness and a burning feeling in the nose.

Where is the study run from?
Maastricht University Medical Center, the Netherlands.

When is the study starting and how long is it expected to run for?
November 2005 to April 2006

Who is funding the study?
Maastricht University Medical Center, the Netherlands.

Who is the main contact?
Mrs Nicole Veldhorst

Contact information

Mrs Nicole Veldhorst
Scientific

P. Debyelaan 25
Maastricht
6229 HX
Netherlands

Study information

Study designSingle-dose randomised-sequence open-label two period crossover pilot study
Primary study designInterventional
Secondary study designRandomised cross over trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titlePharmacokinetics and tolerability of a formulation of midazolam 50 mg/ml nose spray vs midazolam 1 mg/ml intravenously administered in healthy Dutch subjects: a single dose, randomised-sequence, open-label, two-period crossover pilot study
Study objectivesTo investigate pharmacokinetics and tolerability of midazolam in a new formulation, administered as a 50 mg/ml intranasal (IN) spray compared with intravenous (IV) (2.5 mg) administration in healthy adult volunteers.
Ethics approval(s)Medical Ethics Committee, Maastricht University Medical Centre (MUMC), 21/02/2003, MEC-02-143.5
Health condition(s) or problem(s) studiedEpileptic seizures
InterventionIn this cross over study subjects are randomly assigned to receive IN or IV midazolam, with a washout period of at least five days between treatments.

The 50 mg/ml IN midazolam formulation consists of 5 mg midazolam base per 0.1 ml (one spray) and is administered once in one nostril. The IV midazolam solution (2.5 mg) is infused over 10 seconds also once. Blood samples are taken before administration and at regular intervals up to 240 minutes after dosing. The duration of the intervention is 240 minutes.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Midazolam
Primary outcome measurePharmacokinetics of midazolam nose spray (5 mg, 50 mg/mL formulation) compared with intravenous administration (2.5 mg) - Blood samples for pharmacokinetic analysis were collected from an intravenous (IV) cannula at baseline and at 3.5,15, 20, 30, 40, 60, 90,120,180 and 240 minutes post-dose. Pharmacokinetic data [maximum concentration (Cmax), time to maximum plasma concentration (Tmax), biological half life (t1/2), area under the Curve (AUC)] are analysed using two-compartment analysis.
Secondary outcome measuresTolerability of midazolam nose spray (50 mg/mL formulation) - Subjects are instructed to inform the investigator of any untoward effects occuring during the study, including both local adverse events and systemic adverse events. Major expected side effects, like drowsiness and local burning feeling, were registered by a Visual Analogue Scale (VAS) form 0 = no complaint at all to 100 = worst complaint possible, others were described.
Overall study start date01/11/2005
Completion date01/04/2006

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants9
Key inclusion criteria1. Age more than or equal to 18 years, either sex
2. American Society of Anesthesiology patient classification status (ASA) I and II
Key exclusion criteria1. Allergy to benzodiazepines
2. Acute or chronic nasal problems like rhinitis or sinusits
3. Use of benzodiazepines or grapefruit was prohibitied for a week prior to the research
Date of first enrolment01/11/2005
Date of final enrolment01/04/2006

Locations

Countries of recruitment

  • Netherlands

Study participating centre

P. Debyelaan 25
Maastricht
6229 HX
Netherlands

Sponsor information

Maastricht University Medical Centre (Netherlands)
University/education

P.Debeyelaan 25
Maastricht
6229 HX
Netherlands

ROR logo "ROR" https://ror.org/02d9ce178

Funders

Funder type

University/education

Maastricht University Medical Centre (Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/12/2011 Yes No