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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Coeruleus Ltd.
Sponsor:
Information provided by (Responsible Party):
Coeruleus Ltd.
ClinicalTrials.gov Identifier:
NCT01655914
First received: July 30, 2012
Last updated: September 28, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Insomnia
Drug: Flumazenil
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Randomized, Three-way Crossover Study to Assess the Safety and the Pharmacokinetics of Sublingual Flumazenil (CRLS035) in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Coeruleus Ltd.:

Primary Outcome Measures:
  • Bioavailability & Bioequivalence study of sublingual CRLS035 (1.1 mg and 2.2 mg) in a single dose administration [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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]

  • Number of participants with adverse events [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    To determine the number of participants with adverse events to sublingual CRLS035 administration (1.1 mg and 2.2 mg)


Secondary Outcome Measures:
  • Dose Escalation [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.

  • High Fat Diet and Water Consumption effect [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    To evaluate the effect of high fat diet and water consumption on the PK profile.


Estimated Enrollment: 10
Study Start Date: July 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A

Sequence of Exposure:

Sequence A (N=5) Week 1: S/L 1.1 mg Week 2: S/L 2.2 mg Week 3: IV 0.2 mg Week 4: S/L 2.2 mg with 240 ml water

Drug: Flumazenil
Active Comparator: Arm B
Sequence B (N=5) Week 1: IV 0.2 mg Week 2: S/L 2.2 mg Week 3: S/L 1.1 mg Week 4: S/L 2.2 mg with high fat diet
Drug: Flumazenil

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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-at screening.
  3. Body mass index ≥ 18.5 and < 32 kg/m2.
  4. Subject is in good health as determined by a medical history, physical examination and ECG.
  5. 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. Previous exposure to Benzodiazepines and/or non-Benzodiazepine hypnotic drugs within 3 months prior to study initiation.
  3. History of Epilepsy and or anti-epileptic drugs.
  4. Pregnancy or breast feeding.
  5. Clinically relevant ECG abnormalities.
  6. History of alcohol or drug abuse within 3 years prior to the screening visit.
  7. Known hypersensitivity to drugs of the same class as the study treatment, or any excipients of the drug formulation.
  8. Treatment with another investigational drug within 1 month prior to the screening visit.
  9. History of severe head injury.
  10. Any acute or chronic illness
  11. Xerostomia (endogenic or drug induced).
  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: NCT01655914

Contacts
Contact: YAACOV BARUCH, Prof 972 4 8541415 ybaruch@rambam.health.gov.il

Locations
Israel
Rambam Health Care Campus Recruiting
Haifa, Israel, 31096
Contact: Yaacov Baruch, Prof    972 4 8541415    ybaruch@rambam.health.gov.il   
Sponsors and Collaborators
Coeruleus Ltd.
  More Information

No publications provided

Responsible Party: Coeruleus Ltd.
ClinicalTrials.gov Identifier: NCT01655914     History of Changes
Other Study ID Numbers: CRLS002
Study First Received: July 30, 2012
Last Updated: September 28, 2012
Health Authority: Israel: Ministry of Health

Additional relevant MeSH terms:
Flumazenil
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on July 28, 2014