Comparative Bioavailability of Sublingual TNX-102, Oral and Intravenous Cyclobenzaprine in Healthy Adults

Phase 1

Completed

• Conditions: Healthy Adults
• Interventions: Drug: Cyclobenzaprine IV; Drug: SL TNX-102 2.4 mg at pH 3.5; Drug: SL TNX-102 2.4 mg at pH 7.1; Drug: Cyclobenzaprine Tablet

• Registration Number: NCT01634412
• Lead Sponsor: Tonix Pharmaceuticals, Inc.

Brief Summary

Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for bedtime use. The present trial is designed to assess the safety and tolerability of sublingual TNX-102 2.4 mg (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) at pH 3.5 and 7.1 and to compare the bio-availability of sublingual TNX-102 2.4 mg at pH 3.5 and 7.1 and cyclobenzaprine (5 mg tablets, or 2.4 mg iv).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2012-06-25
• Study First Submitted QC: 2012-07-02
• Study First Posted: 2012-07-06
• Primary Completion: 2013-09
• Study Completion: 2014-01
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-24
• Last Update Posted: 2014-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Healthy adults

• Male or female
• Non-smoker
• 18-65 years old
• BMI > 18.5 and < 30.0
• With medically acceptable form of contraception (female only)
• With signed informed consent

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Exclusion Criteria

• Any clinically significant abnormality including ECG abnormalities or vital sign abnormalities (systolic blood pressure < 90 or > 140 mmHg, diastolic blood pressure lower < 50 or > 90 mmHg, or heart rate < 50 or > 100 BPM)
• Any abnormal laboratory test (including positivity for Hep B, Hep C, HIV, and Hemoglobin < 128 g/L (males) or < 115 g/L (females) and hematocrit < 0.37 L/L (males) or < 0.32 L/L (females))
• History of alcohol or drug abuse or dependence within 1 year and/or positive drug, cotinine, or alcohol tests
• Use of any drug (within 30 days), supplement, or food (within 14 days) known to induce or inhibit hepatic drug metabolism prior to study medication
• Positive pregnancy test, breastfeeding or lactating
• Use of medication other than hormonal contraceptives or topical products, including OTC, natural health products, MAO inhibitors
• Participation in an investigational study within 30 days prior to dosing
• Donation of plasma (within 7 days), or donation or loss of blood of 50-499 mL (within30 days), or of > 499 mL (within 56 days) prior to dosing.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclobenzaprine IV	Cyclobenzaprine IV	2.4 mg cyclobenzaprine USP in PBS (0.6 mg/mL) at pH 7.4
SL TNX-102 at pH 3.5	SL TNX-102 2.4 mg at pH 3.5	2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 3.5
SL TNX-102 at pH 7.1	SL TNX-102 2.4 mg at pH 7.1	2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 7.1
Cyclobenzaprine tablets	Cyclobenzaprine Tablet	5 mg cyclobenzaprine tablet once

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of sublingual TNX-102 2.4 mg at pH 3.5 and pH 7.1.	Continuously until the end (day 4) of the study period + Telephone follow-up 7-13 days after dosing (total duration: about 1 month)	Every adverse events occurring during the study period will be reported.
• Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and urine	27 time points per period for blood assessment ; 3 pooled analyses in urine.	Blood samples will be taken per period: within 30 minutes pre-dose and 2, 3.5, 5, 10, 20, 30, and 45 minutes and 1, 2, 2.5, 3, 3.33, 3.67, 4, 4.33, 4.67, 5, 5.5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose. A single urine sample will be collected within 30 minutes pre-dose (one sample), and urine will be pooled from 0-24, 24-48 and 48-72 hours post-dose.

Trial Locations

Locations (1)

PharmaNet, Inc.; 🇨🇦 Quebec City, Quebec, Canada