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

This study has been completed.
Information provided by (Responsible Party):
Tonix Pharmaceuticals, Inc. Identifier:
First received: June 25, 2012
Last updated: September 24, 2014
Last verified: September 2014
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).

Condition Intervention Phase
Healthy Adults
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
Drug: Cyclobenzaprine IV
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Dose, Open-Label, Randomized Study of the Comparative Pharmacokinetics of Sublingual TNX-102 2.4 mg at pH 3.5 and 7.1, Oral Cyclobenzaprine 5 mg Tablets, and Intravenous Cyclobenzaprine 2.4 mg in Healthy Adults

Resource links provided by NLM:

Further study details as provided by Tonix Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • • Measured levels of cyclobenzaprine and norcyclobenzaprine in plasma and urine [ Time Frame: 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.

  • Safety and tolerability of sublingual TNX-102 2.4 mg at pH 3.5 and pH 7.1. [ Time Frame: 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.

Enrollment: 24
Study Start Date: June 2012
Study Completion Date: January 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SL TNX-102 at pH 3.5
2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 3.5
Drug: SL TNX-102 2.4 mg at pH 3.5
1 dose of 2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 3.5, administered as 1 mL held under the tongue for 90 seconds without swallowing
Experimental: SL TNX-102 at pH 7.1
2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 7.1
Drug: SL TNX-102 2.4 mg at pH 7.1
1 dose of 2.4 mg TNX-102 sublingual solution (2.4 mg/mL) in PBS at pH 7.1, administered as 1 mL held under the tongue for 90 seconds without swallowing
Active Comparator: Cyclobenzaprine tablets
5 mg cyclobenzaprine tablet once
Drug: Cyclobenzaprine Tablet
1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water
Active Comparator: Cyclobenzaprine IV
2.4 mg cyclobenzaprine USP in PBS (0.6 mg/mL) at pH 7.4
Drug: Cyclobenzaprine IV
1 dose of 2.4 mg cyclobenzaprine USP in PBS (0.6 mg/mL) at pH 7.4, administered intravenously as a 4 mL bolus injection over 30 seconds


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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 (within30 days), or of > 499 mL (within 56 days) prior to dosing.
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Please refer to this study by its identifier: NCT01634412

Canada, Quebec
PharmaNet, Inc.
Quebec City, Quebec, Canada, G1P 0A2
Sponsors and Collaborators
Tonix Pharmaceuticals, Inc.
Study Chair: Seth M. Lederman, MD Tonix Pharmaceuticals, Inc.
Study Director: Jeffrey P. Kitrelle, MD Tonix Pharmaceuticals, Inc.
Principal Investigator: Denis Audet, MD PharmaNet
  More Information

Responsible Party: Tonix Pharmaceuticals, Inc. Identifier: NCT01634412     History of Changes
Other Study ID Numbers: TNX-CY-F102
Study First Received: June 25, 2012
Last Updated: September 24, 2014

Additional relevant MeSH terms:
Pharmaceutical Solutions
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Tranquilizing Agents
Central Nervous System Depressants
Analgesics, Non-Narcotic
Sensory System Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Neurotransmitter Agents processed this record on May 25, 2017