Safety and Pharmacokinetic Study of Sublingual Flumazenil (CRLS035) in Healthy Adults
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|ClinicalTrials.gov Identifier: NCT01655914|
Recruitment Status : Completed
First Posted : August 2, 2012
Last Update Posted : January 30, 2015
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 or disease||Intervention/treatment||Phase|
|Insomnia||Drug: Flumazenil||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open Label, Randomized, Three-way Crossover Study to Assess the Safety and the Pharmacokinetics of Sublingual Flumazenil (CRLS035) in Healthy Adults|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||December 2010|
|Actual Study Completion Date :||August 2012|
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
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
- 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]
- 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)
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01655914
|Rambam Health Care Campus|
|Haifa, Israel, 31096|