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Completed

NCT Number: NCT01655914

Safety and Pharmacokinetic Study of Sublingual Flumazenil (CRLS035) in Healthy Adults

This study compare the pharmacokinetic (PK) profile of sublingual CRLS035 (two doses) to I.V flumazenil administration.

Selection of study drug dosage: CRLS035 - sublingual Flumazenil will be administrated at a final dosage of 1.1 mg per 100 µl and 2.2 mg (200 µl) in a sublingual spray administration.

Currently, Flumazenil is given as an IV drug with a repetitive administration of doses of 0.2 mg up to 3 mg per hour. As the bioavailability of Flumazenil is expected to be lower than the IV administration, 1.1 mg and 2.2 mg will be tested in sublingual delivery. The suggested doses in this study are very safe according to the following data: first, sublingual and buccal administration of Flumazenil have been detailed previously with similar and higher doses with no side effects, secondly, IV dose may reach 3 mg and thirdly, oral administration has been reported as up to 600 mg/dose.

The purpose of this study is to determine the single dose PK profile of SL CRLS035. This study is designed to collect short-term safety data and to monitor the PK profile of CRLS035.

Primary Objective The primary objective is to determine the single dose safety and PK profile of SL CRLS035 using the marketed IV flumazenil formulation as the comparator.

Secondary Objectives The secondary objectives are to (1) characterize the concentration time course of two dose levels of SL CRLS035 to support dose selection for Phase 2 and 3 studies and to evaluate the safety and tolerability of flumazenil formulations; (2)To evaluate the effect of high fat diet and water consumption on the PK profile.

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Key information

Conditions

Insomnia Dyssomnias Mental Disorders Nervous System Diseases Sleep Disorders, Intrinsic Sleep Initiation and Maintenance Disorders Sleep Wake Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Rambam Health Care Campus

Haifa, 31096, Israel

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • The subject understood and voluntarily signed an informed consent form prior to any study-mandated procedure.
  • Male or female aged ≥18-at screening.
  • Body mass index ≥ 18.5 and < 32 kg/m2.
  • Subject is in good health as determined by a medical history, physical examination and ECG.
  • Negative any use of illicit drug, alcohol (ethanol), stimulants.

Exclusion criteria

  • Any use of medications within 1 month prior to screening visit, except for contraceptive pills.
  • Previous exposure to Benzodiazepines and/or non-Benzodiazepine hypnotic drugs within 3 months prior to study initiation.
  • History of Epilepsy and or anti-epileptic drugs.
  • Pregnancy or breast feeding.
  • Clinically relevant ECG abnormalities.
  • History of alcohol or drug abuse within 3 years prior to the screening visit.
  • Known hypersensitivity to drugs of the same class as the study treatment, or any excipients of the drug formulation.
  • Treatment with another investigational drug within 1 month prior to the screening visit.
  • History of severe head injury.
  • Any acute or chronic illness
  • Xerostomia (endogenic or drug induced).

Treatment and study plan

Flumazenil

Drug

Primary outcomes

  1. Bioavailability & Bioequivalence study of sublingual CRLS035 (1.1 mg and 2.2 mg) in a single dose administration

    Time frame: 3 months

    To determine the Bioavailability and Bioequivalence of sublingual CRLS035 (1.1 and 2.2 mg) in a single dose administration using the marketed IV flumazenil formulation (0.2 mg) as the comparator [Cmax, Tmax, Cmin, Tmin, AUC0-∞, AUC0-t, T1/2, and F]

  2. Number of participants with adverse events

    Time frame: 3 months

    To determine the number of participants with adverse events to sublingual CRLS035 administration (1.1 mg and 2.2 mg)

Secondary outcomes

  1. Dose Escalation

    Time frame: 3 months

    The secondary objectives are to characterize the concentration time course of two dose levels of SL CRLS035 to support dose selection for Phase 2 and 3 studies and to evaluate number of participants with adverse events and tolerability of flumazenil formulations.

  2. High Fat Diet and Water Consumption effect

    Time frame: 3 months

    To evaluate the effect of high fat diet and water consumption on the PK profile.

Sponsors and collaborators

Lead sponsor

Coeruleus Ltd.

Industry

Registry information

Official study title

Open Label, Randomized, Three-way Crossover Study to Assess the Safety and the Pharmacokinetics of Sublingual Flumazenil (CRLS035) in Healthy Adults

Important dates

Study start
2010
Primary completion
2010
Study completion
2012
First posted
Aug 2, 2012
Registry last updated
Jan 30, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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