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

NCT01655914 | Completed Phase 1

• 1 other identifier: CRLS002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Insomnia

Outcome Measures

Primary Outcomes (2)

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

  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 \[Cmax, Tmax, Cmin, Tmin, AUC0-∞, AUC0-t, T1/2, and F\]

  3 months

• Number of participants with adverse events

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

  3 months

Secondary Outcomes (2)

• Dose Escalation

  3 months

• High Fat Diet and Water Consumption effect

  3 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

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

Arm B

ACTIVE COMPARATOR

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

Interventions

Flumazenil DRUG

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Coeruleus Ltd.: lead

Study Sites (1)

Rambam Health Care Campus

Haifa, 31096, Israel

Location

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Flumazenil

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2012
• First Posted: August 2, 2012
• Study Start: July 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: August 1, 2012
• Last Updated: January 30, 2015

Record last verified: 2015-01

Locations

IL (1)