Trial Outcomes & Findings for BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy (BESTFIT) (NCT NCT01903265)

NCT ID: NCT01903265

Last Updated: 2016-12-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

205 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2016-12-23

Participant Flow

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.

Screening for eligibility and washout of restricted medications.

Participant milestones

Participant milestones
Measure
TNX-102 SL 2.8 mg
1 tablet of TNX-102 SL sublingually each day at bedtime for 12 weeks
Placebo
1 tablet of placebo sublingually each day at bedtime for 12 weeks.
Overall Study
STARTED
103
102
Overall Study
COMPLETED
89
85
Overall Study
NOT COMPLETED
14
17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
TNX-102 SL 2.8 mg Tablets
n=103 Participants
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.
Placebo
n=101 Participants
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
n=204 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Age, Categorical
Between 18 and 65 years
103 Participants
n=93 Participants
96 Participants
n=4 Participants
199 Participants
n=27 Participants
Age, Categorical
>=65 years
0 Participants
n=93 Participants
5 Participants
n=4 Participants
5 Participants
n=27 Participants
Age, Continuous
50.7 years
n=93 Participants
49.7 years
n=4 Participants
50.2 years
n=27 Participants
Gender
Female
96 Participants
n=93 Participants
98 Participants
n=4 Participants
194 Participants
n=27 Participants
Gender
Male
7 Participants
n=93 Participants
3 Participants
n=4 Participants
10 Participants
n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Outcome measures
Measure
TNX-102 SL 2.8 mg Tablets
n=103 Participants
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.
Placebo
n=102 Participants
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.
Mean Change From Baseline in Weekly Average of Daily Pain Scores at Week 12
-1.39 units on a scale
Standard Error 0.253
-0.95 units on a scale
Standard Error 0.271

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Outcome measures
Measure
TNX-102 SL 2.8 mg Tablets
n=103 Participants
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.
Placebo
n=102 Participants
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.
30% Responder Analysis of IVRS NRS Pain Assessments at Week 12
34 percentage of participants
20.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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).

Outcome measures

Outcome measures
Measure
TNX-102 SL 2.8 mg Tablets
n=103 Participants
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.
Placebo
n=102 Participants
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.
Change From Baseline to Week 12 in PROMIS T-score for Sleep Disturbance
-8.96 units on a scale
Standard Error 0.993
-5.13 units on a scale
Standard Error 1.029

SECONDARY outcome

Timeframe: Week 12

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

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.

Outcome measures

Outcome measures
Measure
TNX-102 SL 2.8 mg Tablets
n=103 Participants
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.
Placebo
n=102 Participants
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.
Patient Global Impression of Change (PGIC) Responder Status ("Very Much Improved" or "Much Improved" vs All Other Categories) at Week 12
30.1 percentage of participants
16.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Outcome measures
Measure
TNX-102 SL 2.8 mg Tablets
n=103 Participants
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.
Placebo
n=102 Participants
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.
Change From Baseline to Week 12 in FIQ-R Total Score
-15.59 units on a scale
Standard Error 2.079
-8.54 units on a scale
Standard Error 2.133

Adverse Events

TNX-102 SL 2.8 mg Tablets

Serious events: 0 serious events
Other events: 65 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
TNX-102 SL 2.8 mg Tablets
n=103 participants at risk
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.
Placebo
n=101 participants at risk
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.
Hepatobiliary disorders
CHOLECYSTITIS
0.00%
0/103 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
0.99%
1/101 • Number of events 1 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.

Other adverse events

Other adverse events
Measure
TNX-102 SL 2.8 mg Tablets
n=103 participants at risk
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.
Placebo
n=101 participants at risk
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.
Gastrointestinal disorders
hypoaesthesia oral
43.7%
45/103 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
2.0%
2/101 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
Gastrointestinal disorders
Nausea
4.9%
5/103 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
2.0%
2/101 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
Nervous system disorders
Somnolence
1.9%
2/103 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
6.9%
7/101 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
Musculoskeletal and connective tissue disorders
Back pain
4.9%
5/103 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
3.0%
3/101 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
General disorders
Product taste abnormal
7.8%
8/103 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.
0.00%
0/101 • 12 weeks
One placebo patient was never assigned study drug, thereby reducing the placebo group for safety analyses to 101 patients.

Additional Information

Gregory M. Sullivan, MD, Chief Medical Officer

Tonix Pharmaceuticals

Phone: 212 980 9155

Results disclosure agreements

  • Principal investigator is a sponsor employee An industry standard NDA in place with all study investigators.
  • Publication restrictions are in place

Restriction type: OTHER