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

Overview[ - collapse ][ - ]

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 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).
ConditionHealthy Adults
InterventionDrug: 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
PhasePhase 1
SponsorTonix Pharmaceuticals, Inc.
Responsible PartyTonix Pharmaceuticals, Inc.
ClinicalTrials.gov IdentifierNCT01689259
First ReceivedSeptember 14, 2012
Last UpdatedJune 6, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateSeptember 14, 2012
Last Updated DateJune 6, 2013
Start DateSeptember 2012
Estimated Primary Completion DateMarch 2014
Current 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 TNX-102 SL Tablets at 2.4 mg and 4.8 mg. [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.
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleComparative Pharmacokinetics and Safety of TNX-102 SL Tablets and Cyclobenzaprine Oral Tablet in Healthy Adults
Official TitleA 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.
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 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).
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionHealthy Adults
InterventionDrug: 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.
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.
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.
Drug: Cyclobenzaprine tablets
1 x 5 mg cyclobenzaprine tablet, swallowed with 240 mL of room-temperature water
Study Arm (s)
  • Experimental: SL TNX-102 at 2.4 mg
    1 x TNX-102 SL Tablets at 2.4 mg
  • Experimental: SL TNX-102 at 4.8 mg
    2 x TNX-102 SL Tablets at 2.4 mg
  • Experimental: SL TNX-102-A at 2.4 mg
    1 x TNX-102-A (without phosphate) SL Tablet at 2.4 mg
  • Active Comparator: Cyclobenzaprine tablets
    1 x 5 mg cyclobenzaprine oral tablet

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment24
Estimated Completion DateMarch 2014
Estimated Primary Completion DateDecember 2013
Eligibility 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 (within
30 days), or of > 499 mL (within 56 days) prior to dosing.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesCanada

Administrative Information[ + expand ][ + ]

NCT Number NCT01689259
Other Study ID NumbersTNX-CY-F103
Has Data Monitoring CommitteeNo
Information Provided ByTonix Pharmaceuticals, Inc.
Study SponsorTonix Pharmaceuticals, Inc.
CollaboratorsNot Provided
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
Verification DateJune 2013

Locations[ + expand ][ + ]

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