Healthy Adults
Conditions
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.
Interventions
DRUGTreatment A
1 x TNX-102 SL 2.8 mg yellow tablet (commercial manufacturer) to be held under the tongue until dissolved.
DRUGTreatment B
1 x TNX-102 SL 2.8 mg white tablet (original manufacturer) to be held under the tongue until dissolved.
Sponsors
Tonix Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female between 18 and 65 years of age, non-smoker. 2. Body mass index \>18.5 and \<30.0 kg/m2 3. Females of childbearing potential must be willing to use a medically acceptable method of birth control throughout the study. 4. Capable of consent.
Exclusion criteria
1. Any clinically significant abnormality or abnormal laboratory test results found during medical screening 2. Positive hepatitis B, hepatitis C, HIV, urine drug screen, urine cotinine test, or alcohol breath test at screening. 3. History of hypersensitivity to cyclobenzaprine, any of the formulation component, or other related drugs. 4. Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to the first study drug administration. 5. Positive pregnancy test at screening. 6. Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities at screening. 7. History of significant alcohol or drug abuse within one year prior to screening 8. 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. 9. Use of medication other than topical products without significant systemic absorption and hormonal contraceptives 10. Breast-feeding subject. 11. Presence of dentures, tongue piercings with ongoing use of tongue studs/jewelry, orthodontic braces, or surgical manipulations of the tongue.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Plasma Concentration (AUC) of Cyclobenzaprine | 0 to 96 hours | 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. |
| 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. | Continuously until the end (day 5) of each study period + 8-10 days after end of last period (total duration: about 1 month) | The MedDRA® dictionary was used to classify all TEAEs reported during the study by System Organ Class (SOC) and Preferred Term (PT). |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All subjects that were randomized to receive all treatments. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 43 |
| other Total, other adverse events | 18 / 42 | 19 / 43 |
| serious Total, serious adverse events | 0 / 42 | 0 / 43 |
Outcome results
Primary
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.
Time frame: 0 to 96 hours
Population: Subjects who completed the study and for whom the PK profile could be adequately characterized were included in the outcome measures.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Mean Plasma Concentration (AUC) of Cyclobenzaprine | 70066.90 pg*h/mL | Standard Deviation 25158.61 |
| Treatment B | Mean Plasma Concentration (AUC) of Cyclobenzaprine | 64711.53 pg*h/mL | Standard Deviation 22633.07 |
Primary
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).
Time frame: Continuously until the end (day 5) of each study period + 8-10 days after end of last period (total duration: about 1 month)
Population: All subjects who received at least one dose of either Treatment A or Treatment comprised the safety population (N = 43). Of these, 1 subject discontinued from the study after one dose of Treatment B and was replaced with a stand-by. A total 42 subjects completed the study as per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | 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. | 18 Participants |
| Treatment B | 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. | 19 Participants |