Safety and the Efficacy of a Sublingual Administration of Flumazenil to Reverse the Effect of Hypnotic Drugs in Healthy Adults

Double-blind, Randomized, Placebo and Active Controlled Study to Assess the Safety and the Efficacy of a Sublingual Administration of Flumazenil to Reverse the Effect of Hypnotic Drugs in Healthy Adults(Zolpidem or Brotizolam)

The purpose of this study is to evaluate the safety and effectiveness of treatment with sublingual (s/l) Flumazenil in healthy volunteers as reversing the effect of the sleep/hypnotic drugs. This study is designed to collect short-term safety and tolerability data.

In addition, the psychomotor/ cognitive and behavioral effects of Flumazenil will be assessed to monitor the degree and the duration of action in a single use of Flumazenil.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Flumazenil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject understood and voluntarily signed an informed consent form prior to any study-mandated procedure.

2. Male or female aged 18-65 at screening. Women of childbearing potential must have a negative pregnancy test at the screening visit and use a reliable method of contraception during the entire study duration (e.g.

   Contraceptive pill; Intra-uterine device; Contraceptive injection (prolonged-release gestagen); Subdermal implantation;Vaginal ring or Transdermal patch).

3. Body mass index ≥ 18.5 and < 32 kg/m2.
4. Normal sleep habits, i.e. usual self-reported total sleep time > 6 h; usual self-reported time to fall asleep < 30 min; usual bedtime between 10:30 pm and 01:00 am.
5. Subject is in good health as determined by a medical history, physical examination and ECG.
6. Negative any use of illicit drug, alcohol (ethanol), stimulants.

Exclusion Criteria:

1. Any use of medications within 1 month prior to screening visit, except for contraceptive pills.
2. Any sleep associated complains.
3. Previous exposure to Benzodiazepines and/or non-Benzodiazepine hypnotic drugs within 3 months prior to study initiation.
4. History of Epilepsy and or anti-epileptic drugs.
5. Excessive caffeine consumption (≥ 500 mg per day).
6. Pregnancy or breast feeding.
7. Night shift workers within 1 month prior to the screening visit.
8. Clinically relevant ECG abnormalities.
9. History of alcohol or drug abuse within 3 years prior to the screening visit.
10. Cognitive Behavioral Therapy (CBT) started within 1 month prior to the screening visit.
11. Known hypersensitivity to drugs of the same class as the study treatment, or any excipients of the drug formulation.
12. Treatment with another investigational drug within 1 month prior to the screening visit.
13. History of severe head injury.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Brotizolam; Treatment response will be evaluated for each treatment arm. Good Response (GR) - is considered as an improvement of 30% in efficacy parameters of Flumazenil treatment in comparison to placebo	Drug: Flumazenil; Flumazenil- 0.4 mg per 100 µl in a sublingual spray administration; Other Names: Romzicon,; Anexate®,; BRN 4763661,; Flumazenilo (Spanish),; Flumazenilum (Latin),; Flumazepil; Lanexat®,; Mazicon®,; Ro 151788,; Ro-15-1788,; Romazicon®,; UNII-40P7XK9392; Drug: Placebo; Placebo - only excipients with no API
OTHER: Zolpidem; Treatment response will be evaluated for each treatment arm. Good Response (GR) - is considered as an improvement of 30% in efficacy parameters of Flumazenil treatment in comparison to placebo.	Drug: Flumazenil; Flumazenil- 0.4 mg per 100 µl in a sublingual spray administration; Other Names: Romzicon,; Anexate®,; BRN 4763661,; Flumazenilo (Spanish),; Flumazenilum (Latin),; Flumazepil; Lanexat®,; Mazicon®,; Ro 151788,; Ro-15-1788,; Romazicon®,; UNII-40P7XK9392; Drug: Placebo; Placebo - only excipients with no API

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of single dose administration of sublingual Flumazenil 0.4 mg as a reversal drug for the hypnotic effect of sleep/ hypnotic drugs	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy of single dose administration of sublingual Flumazenil 0.4 mg as a reversal drug for the hypnotic effect of sleep/ hypnotic drugs	6 months

Collaborators and Investigators

• Sponsor: Coeruleus Ltd.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: February 17, 2010
• First Submitted That Met QC Criteria: February 18, 2010
• First Posted (ESTIMATE): February 19, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 30, 2015
• Last Update Submitted That Met QC Criteria: January 29, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; GABA Modulators; GABA Agents; Antidotes; Flumazenil
• Other Study ID Numbers: 0076-10-RMB