Bioequivalence Study of TNX-102 SL 2.8 mg Sublingual Tablets From Two Manufacturers.

Study Overview
=================
Brief Summary
-----------------
This study is an open-label, 2-way crossover, single-dose study that is being performed to establish the bioequivalence of TNX-102 SL 2.8 mg tablets from two manufacturers: manufacturer of the Phase 2/3 drug product and manufacturer of the Phase 3 and commercial drug product. This bioequivalence study will confirm (1) the drug product manufactured from these two manufacturers are therapeutically equivalent and (2) the efficacy and safety data obtained in clinical studies using TNX-102 SL from these two manufacturers are comparable.

Detailed Description
-----------------
This will be a single centre, bioequivalence, open-label, randomized, single-dose, 2-period, 2 sequence, crossover study under fasting conditions. Potential subjects will be screened by medical and psychiatric history, and laboratory and physical examinations 2 to 30 days prior to drug administration. All eligible subjects will be admitted to the study unit on Day -1, the day prior to dose administration. Baseline values will be considered the last value obtained before dosing for each assessment. On Day 1, the morning after admission, after all pre-dose assessments have been completed and subjects who remain eligible have agreed to continue, subjects will be randomly assigned to study medication and will receive the assigned test drug. Subjects will be required to fast for at least 10 hours prior to dosing until at least 4 hours post-dose. For each period, subjects will be confined to the study site from at least 10 hours before dosing until after the 24-hour post-dose blood draw. Subjects will come back for all subsequent blood draws. Subjects will be reassessed for eligibility prior to each dosing period.

Official Title
-----------------
A SINGLE-DOSE, RANDOMIZED, OPEN-LABEL, TWO-WAY CROSSOVER BIOEQUIVALENCE STUDY OF TNX-102 SL (CYCLOBENZAPRINE HCL SUBLINGUAL TABLETS) 2.8 mg FROM TWO MANUFACTURERS IN HEALTHY SUBJECTS UNDER FASTING CONDITIONS

Conditions
-----------------
Healthy Adults

Intervention / Treatment
-----------------
* Drug: Treatment A
* Drug: Treatment B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female between 18 and 65 years of age, non-smoker. Body mass index >18.5 and <30.0 kg/m2 Females of childbearing potential must be willing to use a medically acceptable method of birth control throughout the study. Capable of consent. Exclusion Criteria: Any clinically significant abnormality or abnormal laboratory test results found during medical screening Positive hepatitis B, hepatitis C, HIV, urine drug screen, urine cotinine test, or alcohol breath test at screening. History of hypersensitivity to cyclobenzaprine, any of the formulation component, or other related drugs. Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to the first study drug administration. Positive pregnancy test at screening. Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities at screening. History of significant alcohol or drug abuse within one year prior to screening Participation in a clinical trial involving the administration of an investigational or marketed drug within 30 days prior to the first dosing or concomitant participation in an investigational study involving no drug administration. Use of medication other than topical products without significant systemic absorption and hormonal contraceptives Breast-feeding subject. Presence of dentures, tongue piercings with ongoing use of tongue studs/jewelry, orthodontic braces, or surgical manipulations of the tongue.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>1 x TNX-102 SL 2.8 mg yellow tablet (commercial manufacturer) to be held under the tongue until dissolved. | Drug: Treatment A<br>* 1 x TNX-102 SL 2.8 mg yellow tablet (commercial manufacturer) to be held under the tongue until dissolved.<br>* Other names: cyclobenzaprine HCl;|
| Experimental: Treatment B<br>1 x TNX-102 SL 2.8 mg white tablet (original manufacturer) to be held under the tongue until dissolved. | Drug: Treatment B<br>* 1 x TNX-102 SL 2.8 mg white tablet (original manufacturer) to be held under the tongue until dissolved.<br>* Other names: cyclobenzaprine HCl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Plasma Concentration (AUC) of Cyclobenzaprine | Blood samples were collected prior to drug administration and 0.083 (5 min), 0.167 (10 min),0.333 (20 min), 0.500 (30 min), 0.750 (45 min), 1.00, 1.50, 2.00, 2.50, 3.00, 3.33, 3.67, 4.00, 4.33, 4.67, 5.00, 5.50, 6.00, 8.00, 12.0, 16.0, 24.0, 36.0, 48.0, 72.0, and 96.0 hours post-dose in each period. | 0 to 96 hours | 
| Number of Subjects With Treatment-emergent Adverse Events (TEAEs) of Treatment A and Treatment B, Administered as 1 x 2.8 mg TNX-102 SL Under Fasting Conditions. | The MedDRA® dictionary was used to classify all TEAEs reported during the study by System Organ Class (SOC) and Preferred Term (PT). | Continuously until the end (day 5) of each study period + 8-10 days after end of last period (total duration: about 1 month) |