A Comparative Bioavailability and Pharmacokinetic Study of TNX-102 2.4 mg and Cyclobenzaprine 5 mg Tablets in Healthy Adults.

• Sponsor: Tonix Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01490788
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 3
• Duration (Months): 1.4
• Patients Per Site Per Month: 21.7

Study Details

Study Description

Brief Summary

The trial is designed to assess the safety and tolerability of TNX-102 2.4 mg and to compare the bio-availability of TNX-102 2.4 mg and cyclobenzaprine 5 mg tablets under fasting or fed conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Treatment A; Drug: Treatment B; Drug: Treatment C	Phase 1

Detailed Description

Single-center, randomized, open-label, single-dose, three-way-crossover trial is designed to assess the safety and tolerability of TNX-102 2.4 mg (a dose based on the results of a previous Phase 2a, proof-of-concept study - VPI-CY-0001.1) and to compare the rate and extent of absorption of TNX-102 2.4 mg and cyclobenzaprine 5 mg tablets under fasting or fed conditions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Dose, Open-Label, Randomized, Three-Way Crossover Study of the Comparative Bioavailability of TNX-102 2.4 mg and Cyclobenzaprine 5 mg Tablets and of the Effect of Food on the Pharmacokinetics of TNX-102 2.4 mg in Healthy Adults
• Study Start Date: Nov 18, 2011
• Actual Primary Completion Date: Dec 30, 2011
• Actual Study Completion Date: Dec 30, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A 1 x TNX-102 2.4 mg gelcap under fasting conditions	Drug: Treatment A; TNX-102 2.4 mg - 1 gelcap once under fasting conditions.; Other Names: cyclobenzaprine HCl
Experimental: Treatment B 1 x cyclobenzaprine 5 mg immediate release (IR) tablet under fasting conditions	Drug: Treatment B; Cyclobenzaprine 5 mg, 1 tablet once under fasting conditions; Other Names: cyclobenzaprine HCl
Active Comparator: Treatment C 1 x TNX-102 2.4 mg gelcap under fed conditions	Drug: Treatment C; TNX-102 2.4 mg, 1 gelcap once given under fed conditions.; Other Names: cyclobenzaprine HCl

Outcome Measures

Primary Outcome Measures

1. Mean Plasma Concentration (AUC) of Cyclobenzaprine [0 to 96 hours]

   Blood samples were collected pre-dose, 30 min, 1, 1.5, 2, 2.5, 3, 3.33, 3.67, 4, 4.67, 5, 5.5, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose for each treatment period.

2. Incidences of Adverse Events [Continuously until the end (day 5) of each study period + 8-10 days after end of last period (total duration: about 1 month)]

   Every adverse events occurring during the study period will be reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria: Healthy adults

• Male or female

• Non-smoker

• 18-55 years old

• BMI > 18.5 and < 30.0

• With medically acceptable form of contraception (female only).

Exclusion Criteria:

• Any clinically significant abnormality or vital sign abnormalities

• Any abnormal laboratory test

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PharmaNet, Inc.	Québec City	Quebec	Canada	G1P 0A2

Sponsors and Collaborators

• Tonix Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Denis Audet, MD, PharmaNet

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tonix Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01490788
• Other Study ID Numbers: TNX-CY-F101
• First Posted: Dec 13, 2011
• Last Update Posted: Sep 11, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Amitriptyline; Cyclobenzaprine

Study Results

Participant Flow

Arm/Group Title	Treatment A First, Then B, Then C	Treatment A First, Then C, Then B	Treatment B First, Then A, Then C	Treatment B First, Then C, Then A	Treatment C First, Then A, Then B	Treatment C First, Then B, Then A
Arm/Group Description	Single dose of Treatment A (2.4 mg TNX-102 gelcap under fasting conditions), Washout (7 days), Single dose of Treatment B (5 mg cyclobenzaprine IR tablet under fasting conditions), Washout (7 days), Single dose of Treatment C (2.4 mg TNX-102 gelcap under fed conditions)	Single dose of Treatment A (2.4 mg TNX-102 gelcap under fasting conditions), Washout (7 days), Single dose of Treatment C (2.4 mg TNX-102 gelcap under fed conditions), Washout (7 days), Single dose of Treatment B (5 mg cyclobenzaprine IR tablet under fasting conditions)	Single dose of Treatment B (5 mg cyclobenzaprine IR tablet under fasting conditions), Washout (7 days), single dose of Treatment A (2.4 mg TNX-102 gelcap under fasting conditions), Washout (7 days), single dose of Treatment C (2.4 mg TNX-102 gelcap under fed conditions)	Single dose of Treatment B (5 mg cyclobenzaprine IR tablet under fasting conditions), Washout (7 days), single dose of Treatment C (2.4 mg TNX-102 gelcap under fed conditions), Washout (7 days), single dose of Treatment A (2.4 mg TNX-102 gelcap under fasting conditions)	Single dose of Treatment C (2.4 mg TNX-102 gelcap under fed conditions), Washout (7 days), single dose of Treatment A (2.4 mg TNX-102 gelcap under fasting conditions), Washout (7 days), Single dose of Treatment B (5 mg cyclobenzaprine IR tablet under fasting conditions)	Single dose of Treatment C (2.4 mg TNX-102 gelcap under fed conditions), Washout (7 days), Single dose of Treatment B (5 mg cyclobenzaprine IR tablet under fasting conditions), Washout (7 days), single dose of Treatment A (2.4 mg TNX-102 gelcap under fasting conditions)
Period Title: Overall Study
STARTED	5	5	5	5	5	5
COMPLETED	4	5	5	5	5	5
NOT COMPLETED	1	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	All subjects that were randomized to receive all three treatments.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 26.7%
Male	22 73.3%
Region of Enrollment (participants) [Number]
Canada	30 100%

Outcome Measures

1. Primary Outcome

Title	Mean Plasma Concentration (AUC) of Cyclobenzaprine
Description	Blood samples were collected pre-dose, 30 min, 1, 1.5, 2, 2.5, 3, 3.33, 3.67, 4, 4.67, 5, 5.5, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose for each treatment period.
Time Frame	0 to 96 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	All study subject who were administered one TNX-102 2.4 mg gelcap under fasting conditions during the course of the study.	All study subject who were administered one IR tablet of cyclobenzaprine 5 mg under fasting conditions during the course of the study.	All study subject who were administered one TNX-102 2.4 mg, gelcap under fed conditions during the course of the study.
Measure Participants	30	30	30
Mean (Full Range) [pg.hr/mL]	47,074.19	94,874.26	50,263.16

2. Primary Outcome

Title	Incidences of Adverse Events
Description	Every adverse events occurring during the study period will be reported.
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	All study subject who were administered one TNX-102 2.4 mg gelcap under fasting conditions during the course of the study.	All study subject who were administered one IR tablet of cyclobenzaprine 5 mg under fasting conditions during the course of the study.	All study subject who were administered one TNX-102 2.4 mg, gelcap under fed conditions during the course of the study.
Measure Participants	30	30	30
Subjects with Treatment-Emergent Adverse Events	14 46.7%	15 NaN	10 NaN
Subjects with Serious Adverse Events	0 0%	0 NaN	0 NaN
Subjects discontinued due to adverse event	0 0%	0 NaN	0 NaN

Adverse Events

Time Frame	2 months
Arm/Group Title	Treatment A		Treatment B		Treatment C
Arm/Group Description	All study subject who were administered one TNX-102 2.4 mg gelcap under fasting conditions during the course of the study.		All study subject who were administered one IR tablet of cyclobenzaprine 5 mg under fasting conditions during the course of the study.		All study subject who were administered one TNX-102 2.4 mg gelcap under fed conditions during the course of the study.
All Cause Mortality
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/30 (46.7%)		15/30 (50%)		10/30 (33.3%)
Cardiac disorders
Palpitations	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Ear and labyrinth disorders
Ear Discomfort	0/30 (0%)		0/30 (0%)		1/30 (3.3%)
Eye disorders
Photophobia	0/30 (0%)		1/30 (3.3%)		0/30 (0%)
Gastrointestinal disorders
Abdominal distension	2/30 (6.7%)		0/30 (0%)		1/30 (3.3%)
Constipation	3/30 (10%)		1/30 (3.3%)		1/30 (3.3%)
Abdominal Pain	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Diarrhoea	0/30 (0%)		0/30 (0%)		1/30 (3.3%)
Nausea	0/30 (0%)		1/30 (3.3%)		0/30 (0%)
Paraesthesia Oral	0/30 (0%)		0/30 (0%)		1/30 (3.3%)
General disorders
Asthenia	0/30 (0%)		1/30 (3.3%)		0/30 (0%)
Catheter site erythema	0/30 (0%)		1/30 (3.3%)		0/30 (0%)
catheter site pain	1/30 (3.3%)		0/30 (0%)		2/30 (6.7%)
Vessel puncture site haematoma	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Vessel puncture site reaction	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Infections and infestations
Rhinitis	0/30 (0%)		1/30 (3.3%)		0/30 (0%)
Injury, poisoning and procedural complications
Laceration	1/30 (3.3%)		1/30 (3.3%)		0/30 (0%)
Sunburn	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Investigations
Blood Pressure increased	2/30 (6.7%)		1/30 (3.3%)		1/30 (3.3%)
Heart Rate increased	0/30 (0%)		1/30 (3.3%)		1/30 (3.3%)
Mean cell volume increased	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Nervous system disorders
Somnolence	3/30 (10%)		11/30 (36.7%)		2/30 (6.7%)
Headache	1/30 (3.3%)		1/30 (3.3%)		1/30 (3.3%)
Psychiatric disorders
Nervousness	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Renal and urinary disorders
Pollakiuria	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	0/30 (0%)		1/30 (3.3%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/30 (3.3%)		0/30 (0%)		0/30 (0%)
Dry Throat	0/30 (0%)		0/30 (0%)		1/30 (3.3%)
Rhinorrhoea	0/30 (0%)		0/30 (0%)		1/30 (3.3%)
Vascular disorders
Hot Flush	0/30 (0%)		1/30 (3.3%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.