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

Study Overview
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Brief Summary
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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).

Official Title
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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.

Conditions
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Healthy Adults

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |