CLINICAL TRIALS PROFILE FOR FLEXERIL

All Clinical Trials for Flexeril

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00246389 ↗	An Effectiveness and Safety Study of Cyclobenzaprine HCl Alone or in Combination With Ibuprofen for Acute Back or Neck Muscle Pain With Muscle Spasm	Completed	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.	Phase 4	1969-12-31	The purpose of this study is to evaluate the effectiveness and safety of cyclobenzaprine HCl 5 mg (muscle spasm medication) taken three times a day, alone or in combination with ibuprofen 400 mg or 800 mg (pain relief medication) taken three times a day, for the treatment of back or neck muscle pain with muscle spasm.
NCT00610610 ↗	Paroxetine-CR (Paxil-CR) in the Treatment of Patients With Fibromyalgia Syndrome	Completed	GlaxoSmithKline	Phase 4	2002-01-01	Objective: Although there is a high comorbidity of depressive and/or anxiety disorders with fibromyalgia, information on the clinical implications of this comorbidity is limited. We investigated whether a history of depressive and/or anxiety disorders was associated with response to treatment in a double blind, randomized, placebo controlled trial of paroxetine controlled release (CR) in fibromyalgia. Method: One hundred and sixteen fibromyalgia subjects were randomized to receive paroxetine CR (dose 12.5-62.5 mg/day) or placebo for 12 weeks. The Mini International Neuropsychiatric Interview (M.I.N.I-plus) was used to ascertain current or past diagnoses of depressive and anxiety disorders. Patients with current depressive or anxiety disorders were excluded, but those with past diagnoses were enrolled in the trial. Subjective depression and anxiety were assessed using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI); subjects were excluded if they scored greater than 23 on the BDI. Health Status was determined using the 36-Item Short Form Health Survey (SF-36), the Sheehan Disability Scale (SDS), the Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI). The primary outcome was treatment response defined as ≥ 25% reduction in the Fibromyalgia Impact Questionnaire (FIQ) score. Secondary outcomes included changes in scores on the Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I respectively), the Visual Analogue Scale for Pain (VAS) scores and number of tender points.
NCT00610610 ↗	Paroxetine-CR (Paxil-CR) in the Treatment of Patients With Fibromyalgia Syndrome	Completed	Duke University	Phase 4	2002-01-01	Objective: Although there is a high comorbidity of depressive and/or anxiety disorders with fibromyalgia, information on the clinical implications of this comorbidity is limited. We investigated whether a history of depressive and/or anxiety disorders was associated with response to treatment in a double blind, randomized, placebo controlled trial of paroxetine controlled release (CR) in fibromyalgia. Method: One hundred and sixteen fibromyalgia subjects were randomized to receive paroxetine CR (dose 12.5-62.5 mg/day) or placebo for 12 weeks. The Mini International Neuropsychiatric Interview (M.I.N.I-plus) was used to ascertain current or past diagnoses of depressive and anxiety disorders. Patients with current depressive or anxiety disorders were excluded, but those with past diagnoses were enrolled in the trial. Subjective depression and anxiety were assessed using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI); subjects were excluded if they scored greater than 23 on the BDI. Health Status was determined using the 36-Item Short Form Health Survey (SF-36), the Sheehan Disability Scale (SDS), the Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI). The primary outcome was treatment response defined as ≥ 25% reduction in the Fibromyalgia Impact Questionnaire (FIQ) score. Secondary outcomes included changes in scores on the Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I respectively), the Visual Analogue Scale for Pain (VAS) scores and number of tender points.
NCT00778037 ↗	Bioequivalence Study of Cyclobenzaprine Hydrochloride 10 mg Tablets, USP Under Fasting Conditions	Completed	Ranbaxy Laboratories Limited	N/A	2006-09-01	To compare the single-dose oral bioavailability of Cyclobenzaprine hydrochloride 10 mg tablet of Ohm Labs Inc (A subsidiary of Ranbaxy Pharmaceuticals Inc USA.) with Flexeril® 10 mg tablet (containing Cyclobenzaprine hydrochloride 10 mg) of McNeil Consumer & Specialty Pharmaceuticals, in healthy, adult, male, human subjects under fasting condition.
NCT00790270 ↗	Comparison of Ibuprofen, Cyclobenzaprine, or Both for Acute Cervical Strain: A Randomized Clinical Trial	Completed	Stony Brook University	Phase 2	2003-01-01	The purpose of this study is to see whether the combination of a muscle relaxant and anti-inflammatory drug is more effective at relieving pain in patients with neck strains or whiplash than either of the two medications alone.
NCT01028014 ↗	Medication Effects on Periurethral Sensation,Urethral Sphincter Activity and Pressure Flow Parameters	Completed	Astellas Pharma Inc	N/A	2010-04-01	Lower urinary tract symptoms such as urinary leakage and overactive bladder affect millions of American women. Women may develop these problems because the innervation of the muscles of the bladder and urethra are injured. Most research on treating these problems has focused on the abnormalities of the bladder muscle, but newer studies have shown abnormalities in the innervation and muscle function of the urethra. Women with these symptoms may benefit from treatment with medications to improve their urethral function. However, to truly understand what types of medications will help women with these symptoms, the investigators wish to study how these medications affect innervation and muscle function in healthy women who do not have lower urinary tract symptoms.
NCT01028014 ↗	Medication Effects on Periurethral Sensation,Urethral Sphincter Activity and Pressure Flow Parameters	Completed	University of Alabama at Birmingham	N/A	2010-04-01	Lower urinary tract symptoms such as urinary leakage and overactive bladder affect millions of American women. Women may develop these problems because the innervation of the muscles of the bladder and urethra are injured. Most research on treating these problems has focused on the abnormalities of the bladder muscle, but newer studies have shown abnormalities in the innervation and muscle function of the urethra. Women with these symptoms may benefit from treatment with medications to improve their urethral function. However, to truly understand what types of medications will help women with these symptoms, the investigators wish to study how these medications affect innervation and muscle function in healthy women who do not have lower urinary tract symptoms.

Clinical Trial Conditions for Flexeril

Condition Name

Condition Name for Flexeril
Intervention	Trials
Pain	2
Pain, Postoperative	1
Postoperative Pain	1
Sleep Initiation and Maintenance Disorders	1

Condition MeSH

Condition MeSH for Flexeril
Intervention	Trials
Pain, Postoperative	2
Myotonia	1
Sprains and Strains	1
Sleep Wake Disorders	1

Clinical Trial Locations for Flexeril

Trials by Country

Trials by Country for Flexeril
Location	Trials
United States	9
India	1

Trials by US State

Trials by US State for Flexeril
Location	Trials
Georgia	2
California	1
Michigan	1
Illinois	1
Alabama	1

Clinical Trial Progress for Flexeril

Clinical Trial Phase

Clinical Trial Phase for Flexeril
Clinical Trial Phase	Trials
Phase 4	3
Phase 2	2
Phase 1	1

Clinical Trial Status

Clinical Trial Status for Flexeril
Clinical Trial Phase	Trials
Completed	7
Withdrawn	1
Terminated	1

Clinical Trial Sponsors for Flexeril

Sponsor Name

Sponsor Name for Flexeril
Sponsor	Trials
University of Alabama at Birmingham	1
NorthShore University HealthSystem	1
NorthShore University HealthSystem Research Institute	1

Sponsor Type

Sponsor Type for Flexeril
Sponsor	Trials
Other	8
Industry	6

Clinical Trials Update, Market Analysis, and Projections for Flexeril (Cyclobenzaprine)

Clinical Trials Update

Phase 3 RESILIENT Study

The most recent and significant clinical trial update for Flexeril, or more specifically its sublingual formulation TNX-102 SL (cyclobenzaprine HCl), comes from the Phase 3 RESILIENT study conducted by Tonix Pharmaceuticals. This double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy and safety of TNX-102 SL in managing fibromyalgia.

• Primary Endpoint: The study met its primary endpoint, demonstrating a statistically significant reduction in daily pain compared to placebo (p=0.00005) in participants with fibromyalgia. The treatment showed a robust and clinically meaningful analgesic effect size of 0.38[3][4].
• Secondary Endpoints: All six key secondary endpoints, including patient global impression, fibromyalgia-specific symptoms and dysfunction, fatigue, and sleep measures, were significantly improved (all p ≤ 0.001)[3][4].
• Adverse Events: The most common treatment-emergent adverse events were transient and included oral hypoesthesia, abnormal taste, oral paresthesia, and tongue discomfort. No new safety signals were observed[3][4].

Previous Phase 3 RELIEF Study

The positive results from the RESILIENT study follow the earlier successful Phase 3 RELIEF study, which also reported significant pain improvement (p=0.010) over placebo. These two positive Phase 3 trials provide strong support for the planned New Drug Application (NDA) submission to the FDA in the second half of 2024[1][3].

Market Analysis

Market Drivers

The demand for cyclobenzaprine, marketed under brand names like Flexeril and Amrix, is driven by several key factors:

• Aging Population: The increasing age of the population contributes significantly to the demand, as elderly individuals often experience musculoskeletal pain and spasms[2].
• Sedentary Lifestyle and Stress: An increasingly sedentary lifestyle and a rise in stress-related muscular conditions have also contributed to the drug's popularity[2].
• Non-Opioid Alternatives: The growing awareness of the need for non-opioid alternatives to manage pain, given the opioid epidemic, positions cyclobenzaprine as a valuable non-narcotic option for addressing muscle discomfort and tension[2].

Market Trends

• Telemedicine and Digital Health: The integration of telemedicine and digital health platforms has enhanced patient access to prescriptions for cyclobenzaprine and improved patient education, further boosting its market[2].
• Novel Formulations and Combination Therapies: Pharmaceutical companies are exploring novel formulations and combination therapies to stay competitive in the market. The sublingual formulation of TNX-102 SL is a prime example of this trend[2][4].

Competitive Landscape

The market for cyclobenzaprine is influenced by demographic shifts, pain management strategies, and advancements in healthcare delivery. However, it must adapt to changing regulatory landscapes and increasing competition. The potential FDA approval of TNX-102 SL could position Tonix Pharmaceuticals as a leader in the treatment of fibromyalgia, a condition affecting an estimated 6 million to 12 million adults in the U.S.[3].

Market Projections

Projected Demand

The demand for cyclobenzaprine is expected to continue growing due to the factors mentioned above. The aging population and the increasing prevalence of musculoskeletal conditions will drive the need for effective muscle relaxants like cyclobenzaprine.

Economic Projections

• Capital Investments: Setting up a manufacturing plant for cyclobenzaprine involves significant capital investments, including costs for raw materials, machinery, infrastructure, and manpower. However, the return on investment (ROI) and net present value (NPV) are expected to be favorable given the drug's market demand[2].
• Revenue Projections: With the potential FDA approval of TNX-102 SL, Tonix Pharmaceuticals is poised to capture a significant share of the fibromyalgia treatment market. This could lead to substantial revenue growth, especially if the drug becomes a first-line treatment for fibromyalgia[3].

Regulatory Outlook

The planned NDA submission in the second half of 2024 is a critical step for TNX-102 SL. If approved, it would be the first FDA-approved drug for fibromyalgia in over a decade, significantly impacting the market and treatment landscape for this condition[3].

Safety and Tolerability

Adverse Events

The clinical trials have shown that TNX-102 SL is well-tolerated with an adverse event profile comparable to prior studies. The most common adverse events are transient and include oral hypoesthesia, abnormal taste, oral paresthesia, and tongue discomfort. There were no drug-associated changes in systolic or diastolic blood pressure, weight, or sexual side effects[1][3][4].

Conclusion

The clinical trials update for TNX-102 SL, a sublingual formulation of cyclobenzaprine, highlights its significant potential in managing fibromyalgia. The market analysis indicates a strong demand driven by demographic and lifestyle factors, as well as the need for non-opioid pain management alternatives. With favorable safety and tolerability profiles, TNX-102 SL is poised to make a substantial impact on the market if approved by the FDA.

Key Takeaways

• Clinical Success: TNX-102 SL has demonstrated statistically significant and clinically meaningful results in reducing daily pain and improving sleep quality, fatigue, and overall fibromyalgia symptoms.
• Market Demand: The demand for cyclobenzaprine is driven by an aging population, sedentary lifestyle, and the need for non-opioid pain management alternatives.
• Regulatory Outlook: The planned NDA submission in the second half of 2024 could lead to the first FDA-approved drug for fibromyalgia in over a decade.
• Safety and Tolerability: TNX-102 SL has shown a favorable safety and tolerability profile with transient adverse events.

FAQs

What is TNX-102 SL, and how does it differ from traditional Flexeril?

TNX-102 SL is a sublingual formulation of cyclobenzaprine, which differs from traditional Flexeril in its delivery method. It uses transmucosal delivery, bypassing first-pass hepatic metabolism and providing rapid absorption[4].

What were the primary and secondary endpoints of the Phase 3 RESILIENT study?

The primary endpoint was the change from baseline to Week 14 in daily diary pain severity scores. Secondary endpoints included patient global impression, fibromyalgia-specific symptoms and dysfunction, fatigue, and sleep measures[3][4].

How does TNX-102 SL impact sleep quality in patients with fibromyalgia?

TNX-102 SL significantly improved sleep quality, demonstrating target engagement and contributing to the overall improvement in fibromyalgia symptoms[1][3][4].

What are the common adverse events associated with TNX-102 SL?

The most common adverse events include oral hypoesthesia, abnormal taste, oral paresthesia, and tongue discomfort. These events are generally transient and self-limited[1][3][4].

What is the projected timeline for FDA approval of TNX-102 SL?

Tonix Pharmaceuticals plans to submit an NDA to the FDA in the second half of 2024, with potential approval and market supply following thereafter[3].

References

1. Moldofsky H et al. "Psychosom Med" 1975;37:341-51.
2. IMARC Group. "Cyclobenzaprine (Flexeril) Manufacturing Plant Project Report 2024: Industry Trends, Plant Setup, Machinery, Raw Materials, Investment Opportunities, Cost and Revenue."
3. Tonix Pharmaceuticals. "Tonix Pharmaceuticals Announces Highly Statistically Significant and Clinically Meaningful Topline Results in Second Positive Phase 3 Clinical Trial of TNX-102 SL for the Management of Fibromyalgia."
4. eMPR. "Sublingual Cyclobenzaprine Reduces Pain in Patients with Fibromyalgia."

Last updated: 2024-12-31