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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tonix Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01634412
First received: June 25, 2012
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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
Endpoint Classification: Bio-availability Study
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. ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    Every adverse events occurring during the study period will be reported.


Estimated Enrollment: 24
Study Start Date: June 2012
Estimated Study Completion Date: January 2014
Estimated 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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01634412

Locations
Canada, Quebec
PharmaNet, Inc.
Quebec City, Quebec, Canada, G1P 0A2
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Tonix Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01634412     History of Changes
Other Study ID Numbers: TNX-CY-F102
Study First Received: June 25, 2012
Last Updated: June 6, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Cyclobenzaprine
Amitriptyline
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Tranquilizing Agents
Central Nervous System Depressants
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014