Comparative Pharmacokinetics and Safety of TNX-102 SL Tablets and Cyclobenzaprine Oral Tablet in Healthy Adults

A Single-Dose, Open-Label, Randomized, Parallel-Design Study of the Comparative Pharmacokinetics and Safety of TNX-102 2.4 mg SL Tablets (With Phosphate) at 2.4 mg and 4.8 mg, TNX-102-A 2.4 mg SL Tablets (Without Phosphate) at 2.4 mg and Cyclobenzaprine 5 mg Oral Tablets in Healthy Adults.

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 TNX-102 2.4 mg SL Tablets (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) at 2.4 mg and 4.8 mg and to compare the bio-availability of TNX-102 2.4 mg SL Tablets at 2.4 mg and 4.8 mg to that of TNX-102-A 2.4 mg SL Tablets (without phosphate) at 2.4 mg and cyclobenzaprine (5 mg tablets).

Study Overview

• Status: Completed
• Conditions: Healthy Adults
• Intervention / Treatment: Drug: SL TNX-102 at 2.4 mg; Drug: SL TNX-102 at 4.8 mg; Drug: SL TNX-102-A at 2.4 mg; Drug: Cyclobenzaprine tablets

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Quebec City, Quebec, Canada, G1P 0A2
      • PharmaNet, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

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 (within 30 days), or of > 499 mL (within 56 days) prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SL TNX-102 at 2.4 mg; 1 x TNX-102 SL Tablets at 2.4 mg	Drug: SL TNX-102 at 2.4 mg; 1 TNX-102 SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing it.
Experimental: SL TNX-102 at 4.8 mg; 2 x TNX-102 SL Tablets at 2.4 mg	Drug: SL TNX-102 at 4.8 mg; 2 TNX-102 SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing them.
Experimental: SL TNX-102-A at 2.4 mg; 1 x TNX-102-A (without phosphate) SL Tablet at 2.4 mg	Drug: SL TNX-102-A at 2.4 mg; 1 TNX-102-A SL Tablet at 2.4 mg held under the tongue until dissolution, without swallowing or chewing it.
Active Comparator: Cyclobenzaprine tablets; 1 x 5 mg cyclobenzaprine oral tablet	Drug: Cyclobenzaprine tablets; 1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and 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.	27 time points per period for blood assessment ; 3 pooled analyses in urine.
Safety and tolerability of TNX-102 SL Tablets at 2.4 mg and 4.8 mg.	Every adverse events occurring during the study period will be reported.	Continuously until the end (day 4) of the study period + Telephone follow-up 7-13 days after dosing (total duration: about 1 month)

Collaborators and Investigators

• Sponsor: Tonix Pharmaceuticals, Inc.
• Investigators: Study Chair: Seth M. Lederman, MD, Tonix Pharmaceuticals, Inc.; Study Director: Jeffrey P. Kitrelle, MD, Tonix Pharmaceuticals, Inc.; Principal Investigator: Denis Audet, MD, PharmaNet

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 14, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Estimate): September 26, 2014
• Last Update Submitted That Met QC Criteria: September 24, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Tricyclic; Neuromuscular Agents; Muscle Relaxants, Central; Cyclobenzaprine
• Other Study ID Numbers: TNX-CY-F103