Clinical trial NCT01655914: Safety and Pharmacokinetic Study of Sublingual Flumazenil (CRLS035) in Healthy Adults
Official title: Open Label, Randomized, Three-way Crossover Study to Assess the Safety and the Pharmacokinetics of Sublingual Flumazenil (CRLS035) in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insomnia
Lead sponsor: Coeruleus Ltd.
Sponsor class: INDUSTRY
First posted: 2012-08-02
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Bioavailability & Bioequivalence study of sublingual CRLS035 (1.1 mg and 2.2 mg) in a single dose administration
timeFrame: 3 months
measure: Number of participants with adverse events
timeFrame: 3 months
Secondary outcomes:
measure: Dose Escalation
timeFrame: 3 months
measure: High Fat Diet and Water Consumption effect
timeFrame: 3 months
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Health Care Campus
Study officials:
References: