Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia (RE-AFFIRM)

A Phase 3, Double-Blind, Randomized, Multicenter, Placebo-Controlled Study To Evaluate The EFFIcacy and Safety of TNX-102 SL Tablets Taken Daily At Bedtime In Patients With FibRoMyalgia

The present trial is designed to assess the safety and efficacy of TNX-102 SL 2.8 mg tablets, taken daily at bedtime after 12 weeks of treatment in patients with fibromyalgia.

The use of low-dose sublingual formulation of cyclobenzaprine (TNX-102 SL) dosed nightly for fibromyalgia is supported by the results of TNX-CY-F202 Phase 2b study -- the results provide strong evidence that TNX-102 SL 2.8 mg dosed nightly results in beneficial effects upon pain, sleep and other FM symptomatology.

Study Overview

• Status: Terminated
• Conditions: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Intervention / Treatment: Drug: Placebo SL Tablet; Drug: TNX-102 SL Tablet, 2.8 mg

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
  • Arizona
    • Phoenix, Arizona, United States, 85032
  • California
    • Oceanside, California, United States, 92056
    • San Diego, California, United States, 92103
  • Florida
    • Brandon, Florida, United States, 33511
    • DeLand, Florida, United States, 32720
    • Ocala, Florida, United States, 34471
    • Orlando, Florida, United States, 32801
    • Tampa, Florida, United States, 33613
    • Tampa, Florida, United States, 33614
    • West Palm Beach, Florida, United States, 33409
  • Indiana
    • Evansville, Indiana, United States, 47714
    • Indianapolis, Indiana, United States, 46260
  • Mississippi
    • Jackson, Mississippi, United States, 39202
  • Nevada
    • Las Vegas, Nevada, United States, 89102
  • New York
    • Cedarhurst, New York, United States, 11516
    • Williamsville, New York, United States, 14221
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
  • North Dakota
    • Fargo, North Dakota, United States, 58103
  • Ohio
    • Canton, Ohio, United States, 44718
    • Cincinnati, Ohio, United States, 45219
  • Oregon
    • Medford, Oregon, United States, 97504
    • Portland, Oregon, United States, 97210
    • Salem, Oregon, United States, 97301
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
  • Rhode Island
    • Warwick, Rhode Island, United States, 02888
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
  • Texas
    • Dallas, Texas, United States, 75231
  • Utah
    • Salt Lake City, Utah, United States, 84102
  • Washington
    • Seattle, Washington, United States, 98104
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Primary Fibromyalgia (2010 ACR criteria)
• Male or female 18-75 years old
• Patients currently receiving pharmacologic treatment for depression should have been clinically stable for at least 3 months prior to randomization, and on stable doses of antidepressants during this 3 month time frame.
• Willing and able to withdraw specific therapies (ask PI)
• If female, medically acceptable form of contraception or not of child bearing potential.
• Provide written informed consent to participate.
• Willing and able to comply with all protocol specified requirement.

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-out specific medications (ask PI)
• Known hypersensitivity to cyclobenzaprine
• Others: seizure disorders, severe/untreated sleep apnea, BMI>45

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo SL Tablet; 1 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks	Drug: Placebo SL Tablet; Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.; Other Names: Placebo sublingual tablets
Experimental: TNX-102 SL Tablet, 2.8 mg; 1 x TNX-102 SL 2.8 mg Tablet taken sublingually each day at bedtime for 12 weeks	Drug: TNX-102 SL Tablet, 2.8 mg; Patients will take 1 tablet of randomly assigned study drug sublingually each day at bedtime starting on Day 0 for 12 weeks.; Other Names: Low dose cyclobenzaprine sublingual tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Mean Pain Score	The primary efficacy endpoint is the proportion of patients with a ≥30% improvement from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score using an 11-point (0-10) numeric response scale (NRS). A score of 0 indicates "no pain at all", and a score of 10 indicates "worst possible pain".	Day 1, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Global Impression of Change (PGIC)	Proportion of patients with a PGIC rating of "very much improved" or "much improved" at 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.	Week 12
Fibromyalgia Impact Questionnaire (FIQR) Revised, Symptoms Domain	Change from Baseline in the FIQR symptoms domain score at Week 12. The FIQ-R symptom domain is composed of 10 questions. All questions are based on an 11-point numerical rating scale (NRS) of 0-10, with 10 being "worst." Symptom domain scores range from 0-100, with higher scores reflecting worse status.	Day 1, Week 12
Fibromyalgia Impact Questionnaire (FIQR) Revised, Functional Domain Score	Change from Baseline in the FIQR function domain score at Week 12. The FIQ-R functional domain score is composed of 9 questions which are rated on an 11-point numerical rating scale (NRS) of 0-10, with 10 being "worst." FIQ-R functional domain scores can range from 0-90, with higher scores reflecting worsening status.	Day 1, Week 12
Daily Diary Sleep	Change from Baseline in the weekly average of the daily diary assessment of sleep quality at Week 12. Daily sleep quality was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse sleep.	Week 12
Patient Reported Outcomes Measurement System (PROMIS), Sleep Disturbance	Change from Baseline in the PROMIS score for sleep disturbance at 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. 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).	Day 1, Week 12
Patient Reported Outcomes Measurement System (PROMIS), Fatigue	Change from Baseline in the PROMIS score for fatigue at Week 12. The Patient-Reported Outcome Measurement Information System (PROMIS) fatigue 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).	Week 12
Daily Diary Pain	Change from baseline to Week 12 in the weekly average of the daily self-reported average pain severity score. Average daily pain was measured using an 11-point (0-10) numerical rating scale (NRS), with higher scores representing worse pain. Weekly averages were calculated based on the reported daily scores.	Week -1 (Day -7 to Day -1), Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of TNX-102 SL Tablets (Incidence of Adverse Events)	Incidence of Adverse Events	Continuously throughout the treatment period (total duration: about 3 months)
Safety of TNX-102 SL Tablets (Changes from Baseline in clinical laboratory tests)	Changes from Baseline in clinical laboratory tests	Continuously throughout the treatment period (total duration: about 3 months)
Safety of TNX-102 SL Tablets (Changes from Baseline in vital signs)	Changes from Baseline in vital signs	Continuously throughout the treatment period (total duration: about 3 months)
Safety of TNX-102 SL Tablets (Changes from Baseline in physical examination findings including examination of the oral cavity)	Changes from Baseline in physical examination findings including examination of the oral cavity	Continuously throughout the treatment period (total duration: about 3 months)
Safety of TNX-102 SL Tablets (Monitoring suicidality using the C-SSRS)	Monitoring suicidality using the Columbia-Suicide Severity Rating Scale (C-SSRS)	Continuously throughout the treatment period (total duration: about 3 months)
Safety of TNX-102 SL Tablets (Changes from Baseline in BDI-II scores)	Changes from Baseline in Beck Depression Inventory Scores (BDI-II) scores	Continuously throughout the treatment period (total duration: about 3 months)

Collaborators and Investigators

• Sponsor: Tonix Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2016
• Primary Completion (Actual): September 13, 2016
• Study Completion (Actual): September 13, 2016

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (Estimated): July 12, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pain; Sleep; Fibromyalgia; FM
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Fibromyalgia; Myofascial Pain Syndromes; Muscular Diseases; Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Rheumatic Diseases; Collagen Diseases; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Neuromuscular Agents; Muscle Relaxants, Central; Antidepressive Agents, Tricyclic; Cyclobenzaprine
• Other Study ID Numbers: TNX-CY-F302