BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy (BESTFIT) (BESTFIT)

• ClinicalTrials.gov Identifier: NCT01903265
• Recruitment Status: Completed
• First Posted: July 19, 2013
• Results First Posted: December 23, 2016
• Last Update Posted: December 23, 2016
• Sponsor: Tonix Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Tonix Pharmaceuticals, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Primary Fibromyalgia
• Interventions: Drug: TNX-102 SL 2.8mg; Drug: Placebo
• Enrollment: 205

Participant Flow

Recruitment Details	A total of 205 patients were randomized to either TNX-102 SL or placebo; however, one patient was randomized in error (to the placebo group) and was not dispensed any study drug. Therefore, all disposition and safety tables are based on the safety population of 204 patients. Of these, 174 patients completed the study.
Pre-assignment Details	Screening for eligibility and washout of restricted medications.

Arm/Group Title	TNX-102 SL 2.8 mg	Placebo
Arm/Group Description	1 tablet of TNX-102 SL sublingually each day at bedtime for 12 weeks	1 tablet of placebo sublingually each day at bedtime for 12 weeks.
Period Title: Overall Study
Started	103	102
Completed	89	85
Not Completed	14	17

Baseline Characteristics

Arm/Group Title		TNX-102 SL 2.8 mg Tablets	Placebo	Total
Arm/Group Description		1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.	1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks. (One patient randomized in error never received study drug and therefore is not included in this table.)	Total of all reporting groups
Overall Number of Baseline Participants		103	101	204
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	103 participants	101 participants	204 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	103 100.0%	96 95.0%	199 97.5%
	>=65 years	0 0.0%	5 5.0%	5 2.5%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	103 participants	101 participants	204 participants
		50.7; (20 to 64)	49.7; (19 to 65)	50.2; (19 to 65)
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	103 participants	101 participants	204 participants
	Female	96 93.2%	98 97.0%	194 95.1%
	Male	7 6.8%	3 3.0%	10 4.9%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Weekly Average of Daily Pain Scores at Week 12
Description	Daily pain scores were assessed using a 24-hour recall response provided by each patient via an interactive voice response system (IVRS) daily telephone diary. Average daily pain was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse pain. Jump to control was used to replace missing data in each treatment arm.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Intention-to-treat (ITT) population: all randomized patients

Arm/Group Title	TNX-102 SL 2.8 mg Tablets	Placebo
Arm/Group Description:	1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.	1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
Overall Number of Participants Analyzed	103	102
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-1.39 (0.253)	-0.95 (0.271)

2. Secondary Outcome

Title	30% Responder Analysis of IVRS NRS Pain Assessments at Week 12
Description	The weekly averages of daily pain scores were calculated using the daily, 24-hour-recall, IVRS NRS pain assessments. Patients who had at least a 30% improvement from baseline to week 12 in weekly average of daily pain scores were considered responders.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Intention-to-treat (ITT) population: all randomized patients.

Arm/Group Title	TNX-102 SL 2.8 mg Tablets	Placebo
Arm/Group Description:	1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.	1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
Overall Number of Participants Analyzed	103	102
Measure Type: Number; Unit of Measure: percentage of participants
	34	20.6

3. Secondary Outcome

Title	Change From Baseline to Week 12 in PROMIS T-score for Sleep Disturbance
Description	The Patient-Reported Outcome Measurement Information System (PROMIS) sleep disturbance instrument consists of 8 items in which responses are scored 1 to 5 for each item. A higher score on 5 of the 8 items reflects a worse outcome, whereas a higher score on 3 items reflects an improved outcome; therefore, the directionality of the 8 item scores are first synchronized prior to calculation of the total raw score. PROMIS scores are presented as T-scores in which the raw score has been rescaled into a standardized score with a mean of 50 and a standard deviation of 10. Higher T-scores represent more of the concept being measured (in this case, sleep disturbance).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Intention-to-treat (ITT) population: all randomized patients

Arm/Group Title	TNX-102 SL 2.8 mg Tablets	Placebo
Arm/Group Description:	1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.	1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
Overall Number of Participants Analyzed	103	102
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-8.96 (0.993)	-5.13 (1.029)

4. Secondary Outcome

Title	Patient Global Impression of Change (PGIC) Responder Status ("Very Much Improved" or "Much Improved" vs All Other Categories) at Week 12
Description	The PGIC is a 7-point scale (1=very much improved; 7=very much worse) that assesses the patient's perception of the overall change in his/her fibromyalgia symptoms since entering the study. Scores of 1 and 2 were considered responders.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Intention-to-treat (ITT) population: all randomized patients

Arm/Group Title	TNX-102 SL 2.8 mg Tablets	Placebo
Arm/Group Description:	1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.	1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
Overall Number of Participants Analyzed	103	102
Measure Type: Number; Unit of Measure: percentage of participants
	30.1	16.7

5. Secondary Outcome

Title	Change From Baseline to Week 12 in FIQ-R Total Score
Description	The Fibromyalgia Impact Questionnaire (revised) FIQ-R is made up of 3 domains: functional (9 questions), overall (2 questions) and symptoms (10 questions). All questions are based on an 11-point numerical rating scale (NRS) of 0-10, with 10 being "worst." Total FIQ-R scores can range from 0-100, with higher scores reflecting worsening status. The patient's total score on the FIQ-R was assessed at Visits 2, 3, 4, 5, and 6 (Week 12). Jump to control was used to replace missing data in each treatment arm.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Patients in the Intention-to-treat (ITT) population: all randomized patients

Arm/Group Title	TNX-102 SL 2.8 mg Tablets	Placebo
Arm/Group Description:	1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.	1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
Overall Number of Participants Analyzed	103	102
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-15.59 (2.079)	-8.54 (2.133)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
Arm/Group Title	TNX-102 SL 2.8 mg Tablets		Placebo
Arm/Group Description	1 x TNX-102 SL 2.8mg Tablet taken sublingually each day at bedtime for 12 weeks. TNX-102 SL 2.8mg Tablets: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.		1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks. Placebo: Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
All-Cause Mortality
	TNX-102 SL 2.8 mg Tablets		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	TNX-102 SL 2.8 mg Tablets		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0.00%)		1/101 (0.99%)
Hepatobiliary disorders
CHOLECYSTITIS * 1	0/103 (0.00%)	0	1/101 (0.99%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (16.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	TNX-102 SL 2.8 mg Tablets		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/103 (63.11%)		14/101 (13.86%)
Gastrointestinal disorders
hypoaesthesia oral * 1	45/103 (43.69%)		2/101 (1.98%)
Nausea * 1	5/103 (4.85%)		2/101 (1.98%)
General disorders
Product taste abnormal * 1	8/103 (7.77%)		0/101 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain * 1	5/103 (4.85%)		3/101 (2.97%)
Nervous system disorders
Somnolence * 1	2/103 (1.94%)		7/101 (6.93%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (16.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

An industry standard NDA in place with all study investigators.

Results Point of Contact

• Name/Title: Gregory M. Sullivan, MD, Chief Medical Officer
• Organization: Tonix Pharmaceuticals
• Phone: 212 980 9155 ext 117
• EMail: Gregory.Sullivan@TonixPharma.com

• Responsible Party: Tonix Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01903265
• Other Study ID Numbers: TNX-CY-F202
• First Submitted: July 12, 2013
• First Posted: July 19, 2013
• Results First Submitted: July 15, 2016
• Results First Posted: December 23, 2016
• Last Update Posted: December 23, 2016