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.

Tracking Information

• First Submitted Date: July 12, 2013
• First Posted Date: July 19, 2013
• Results First Submitted Date: July 15, 2016
• Results First Posted Date: December 23, 2016
• Last Update Posted Date: December 23, 2016
• Study Start Date: September 2013
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2016)

Mean Change From Baseline in Weekly Average of Daily Pain Scores at Week 12 [ Time Frame: Baseline, Week 12 ]

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.

Original Primary Outcome Measures (submitted: July 18, 2013)

Patient-Perceived Pain [ Time Frame: Weeks 12 or early termination mean change of perceived average pain intensity from baseline ]

The weekly mean change from baseline of the daily patient-perceived average pain intensity will be assesed from the records of the 24-hour recall responses of the patient via a daily telephone diary, using an 11-point numeric assessment of their pain (0=no pain to 10=worst possible pain). Patients will be asked to complete this assessment on a daily basis during the pre-treatment run-in period and throughout the double-blind treatment period

Current Secondary Outcome Measures (submitted: October 31, 2016)

• 30% Responder Analysis of IVRS NRS Pain Assessments at Week 12 [ Time Frame: Baseline, Week 12 ]
  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.
• Change From Baseline to Week 12 in PROMIS T-score for Sleep Disturbance [ Time Frame: Baseline, Week 12 ]
  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).
• Patient Global Impression of Change (PGIC) Responder Status ("Very Much Improved" or "Much Improved" vs All Other Categories) at Week 12 [ Time Frame: Week 12 ]
  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.
• Change From Baseline to Week 12 in FIQ-R Total Score [ Time Frame: Baseline, Week 12 ]
  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.

Original Secondary Outcome Measures (submitted: July 18, 2013)

• Patient's Global Impression of Change [ Time Frame: Weeks 2, 4, 8 and 12 or early termination ]
• Fibromyalgia Impact Questionnaire [ Time Frame: Baseline and weeks 2, 4, 8 and 12 ]
• Patient pain improvement response rate [ Time Frame: Weekly ]
• SF-36 Physical Component score [ Time Frame: Baseline and weeks 4, 8 and 12 ]
• Safety of TNX-102 SL Tablets [ Time Frame: Continuously throughout the treatment period (total duration: about 3 months) ]
  Every adverse events occurring during the study period will be reported.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy (BESTFIT)
• Official Title: A Phase 2b, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TNX-102 SL Tablets Taken at Bedtime in Patients With Fibromyalgia
• Brief Summary: TNX-102 capsules [formerly known as very low dose (VLD) cyclobenzaprine] at bedtime have shown promise as a treatment of fibromyalgia, but the drug required new formulation technology for bedtime use. The present trial was designed to assess the safety and efficacy of TNX-102 SL 2.8 mg tablets, taken daily at bedtime over 12 weeks to treat fibromyalgia.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Primary Fibromyalgia

Intervention

• Drug: TNX-102 SL 2.8mg
  Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
  Other Name: Low dose cyclobenzaprine sublingual tablets
• Drug: Placebo
  Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.
  Other Name: Placebo sublingual tablets

Study Arms

• Experimental: TNX-102 SL 2.8 mg
  Patients will take 1 tablet of TNX-102 SL sublingually each day at bedtime for 12 weeks.
  Intervention: Drug: TNX-102 SL 2.8mg
• Placebo Comparator: Placebo
  Patients will take 1 tablet of placebo sublingually each day at bedtime for 12 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 1, 2015): 205
• Original Estimated Enrollment (submitted: July 18, 2013): 120
• Actual Study Completion Date: September 2014
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of primary Fibromyalgia (ACR criteria)
• Male or female 18-65 years old
• For patients with major depressive disorders only: clinically stable, no suicidal risk and stable anti-depressent therapy
• Willing and able to withdraw specific therapies (ask PI)
• Medically acceptable form of contraception (female only)
• Signed informed consent

Exclusion Criteria:

• Arthritis, lupus and other systemic auto-immune diseases
• Regional or persistent pain that could interfere with assessment of fibromyalgia pain
• Bipolar and psychotic disorders
• Increased risk of suicide
• Significant clinical (cardiac, systemic infection, systemic corticosteroid requirement, drug/alcohol abuse) or laboratory abnormalities.
• Inability to wash-off specific medications (ask PI)
• Known hypersensitivity to cyclobenzaprine
• Others: seizure disorders, sleep apnea, continuous positive airway pressure (CPAP) use, BMI>40

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01903265
• Other Study ID Numbers: TNX-CY-F202
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Tonix Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tonix Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Mark R. Schmal; Premier Research Group plc
• Study Chair: Daniel J. Clauw, MD; Ann Arbor, MI

• PRS Account: Tonix Pharmaceuticals, Inc.
• Verification Date: October 2016