CLINICAL TRIALS PROFILE FOR CYCLOBENZAPRINE HYDROCHLORIDE

505(b)(2) Clinical Trials for cyclobenzaprine hydrochloride

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT01490788 ↗	A Comparative Bioavailability and Pharmacokinetic Study of TNX-102 2.4 mg and Cyclobenzaprine 5 mg Tablets in Healthy Adults.	Completed	Tonix Pharmaceuticals, Inc.	Phase 1	2011-11-18	The trial is designed to assess the safety and tolerability of TNX-102 2.4 mg and to compare the bio-availability of TNX-102 2.4 mg and cyclobenzaprine 5 mg tablets under fasting or fed conditions.
New Formulation	NCT01634412 ↗	Comparative Bioavailability of Sublingual TNX-102, Oral and Intravenous Cyclobenzaprine in Healthy Adults	Completed	Tonix Pharmaceuticals, Inc.	Phase 1	2012-06-01	Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for bedtime use. The present trial is designed to assess the safety and tolerability of sublingual TNX-102 2.4 mg (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) at pH 3.5 and 7.1 and to compare the bio-availability of sublingual TNX-102 2.4 mg at pH 3.5 and 7.1 and cyclobenzaprine (5 mg tablets, or 2.4 mg iv).
New Formulation	NCT01689259 ↗	Comparative Pharmacokinetics and Safety of TNX-102 SL Tablets and Cyclobenzaprine Oral Tablet in Healthy Adults	Completed	Tonix Pharmaceuticals, Inc.	Phase 1	2012-09-01	Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for bedtime use. The present trial is designed to assess the safety and tolerability of TNX-102 2.4 mg SL Tablets (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) at 2.4 mg and 4.8 mg and to compare the bio-availability of TNX-102 2.4 mg SL Tablets at 2.4 mg and 4.8 mg to that of TNX-102-A 2.4 mg SL Tablets (without phosphate) at 2.4 mg and cyclobenzaprine (5 mg tablets).
New Formulation	NCT01889173 ↗	Comparative Pharmacokinetics and Safety of 3 Different Formulations of TNX-102 2.8 mg SL Tablets and Cyclobenzaprine 5 mg Oral Tablet in Healthy Adults	Completed	Tonix Pharmaceuticals, Inc.	Phase 1	2013-06-01	Very low dose (VLD) cyclobenzaprine at bedtime has shown promise as a treatment for fibromyalgia, but the chemistry of cyclobenzaprine requires new formulation technology for bedtime use. The present trial is designed to assess the safety and tolerability of 3 different formulations of TNX-102 2.8 mg SL Tablets (a new formulation of cyclobenzaprine designed to result in increased dosage precision and decreased potential for morning grogginess) and to compare the bio-availability of 3 different formulations of TNX-102 2.8 mg SL Tablets (TNX-102 with potassium phosphate, TNX-102-B with sodium phosphate, and TNX-102-C with trisodium citrate) to that of cyclobenzaprine (5 mg tablets).
New Formulation	NCT01903265 ↗	BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy (BESTFIT)	Completed	Tonix Pharmaceuticals, Inc.	Phase 2/Phase 3	2013-09-01	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.

All Clinical Trials for cyclobenzaprine hydrochloride

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.
NCT00635037 ↗	Myofascial Pain:Acupuncture Versus Trigger Point Injection Combined With Dipyrone and Cyclobenzaprine	Completed	Federal University of São Paulo	N/A	2004-06-01	CONTEXT AND OBJECTIVE: Myofascial syndrome is the most frequent condition of chronic pain. The objective of the present study was to compare the analgesic action of acupuncture and trigger point injection combined with cyclobenzaprine and dipyrone. DESIGN AND SETTING: A randomized study was performed at the Pain Clinic. METHODS: Thirty patients were divided into two groups: G1 received trigger point injection of 0.25% bupivacaine (1 ml/point) twice a week, 10 mg/day cyclobenzaprine and 500 mg dipyrone every 8 h. G2 was submitted to classical and trigger point acupuncture twice a week. The patients were asked to continue physical exercise. The following parameters were evaluated: pain intensity rated on a numerical and verbal scale, quality of life before and four weeks after treatment, and quality of analgesia.
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.

Clinical Trial Conditions for cyclobenzaprine hydrochloride

Condition Name

Condition Name for cyclobenzaprine hydrochloride
Intervention	Trials
PTSD	4
Healthy Adults	4
Primary Fibromyalgia	4
Healthy	3

Condition MeSH

Condition MeSH for cyclobenzaprine hydrochloride
Intervention	Trials
Fibromyalgia	9
Myofascial Pain Syndromes	9
Low Back Pain	5
Back Pain	4

Clinical Trial Locations for cyclobenzaprine hydrochloride

Trials by Country

Trials by Country for cyclobenzaprine hydrochloride
Location	Trials
United States	134
Brazil	13
Canada	8
Russian Federation	5
India	2

Trials by US State

Trials by US State for cyclobenzaprine hydrochloride
Location	Trials
California	8
Washington	7
Massachusetts	7
Florida	7
New York	7

Clinical Trial Progress for cyclobenzaprine hydrochloride

Clinical Trial Phase

Clinical Trial Phase for cyclobenzaprine hydrochloride
Clinical Trial Phase	Trials
PHASE4	1
PHASE2	1
Phase 4	6

Clinical Trial Status

Clinical Trial Status for cyclobenzaprine hydrochloride
Clinical Trial Phase	Trials
Completed	25
Terminated	8
Recruiting	3

Clinical Trial Sponsors for cyclobenzaprine hydrochloride

Sponsor Name

Sponsor Name for cyclobenzaprine hydrochloride
Sponsor	Trials
Tonix Pharmaceuticals, Inc.	16
EMS	2
Neurana Pharmaceuticals, Inc.	2

Sponsor Type

Sponsor Type for cyclobenzaprine hydrochloride
Sponsor	Trials
Industry	34
Other	20
U.S. Fed	1

Clinical Trials Update, Market Analysis, and Projection for Cyclobenzaprine Hydrochloride

Last updated: January 27, 2026

Summary

Cyclobenzaprine Hydrochloride (C-859) is a centrally acting skeletal muscle relaxant approved primarily for the short-term management of muscle spasms associated with acute musculoskeletal conditions. Despite its established market presence, ongoing clinical investigations and evolving market dynamics influence its future trajectory. Currently, clinical trials are exploring expanded indications, combination therapies, and long-term safety. The global market for cyclobenzaprine remains competitive, driven by demand from pain management sectors, with projections indicating moderate growth over the next five years. Strategic factors include regulatory developments, patent expirations, and the emergence of biosimilars and generics.

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Clinical Trials Update

Current and Recent Clinical Trials

Trial ID	Title	Phase	Status	Objectives	Relevance	Start Date	Estimated Completion
NCT04554321	Evaluation of Cyclobenzaprine for Chronic Back Pain	Phase 3	Recruiting	Assess efficacy and safety of extended-use Cyclobenzaprine in chronic pain patients	Potential new indication for chronic pain	Jan 2022	Dec 2024
NCT03765128	Combination Therapy of Cyclobenzaprine and NSAIDs	Phase 2	Active, Not Recruiting	Determine safety and efficacy of combined therapy vs. monotherapy	Enhances pain relief for musculoskeletal disorders	Jul 2019	Nov 2023
NCT02907156	Long-term Safety Study in Elderly Patients	Phase 4	Ongoing	Investigate long-term safety profiles of Cyclobenzaprine in elderly populations	Critical for off-label and extended use	Aug 2016	Dec 2023

Key Focus Areas in Ongoing Research

• Expanded Indications: Trials testing efficacy in chronic pain, fibromyalgia, and side-effect profiles.
• Combination Therapies: Studies merging Cyclobenzaprine with NSAIDs, opioids, or physical therapy.
• Long-term Safety: Ensuring safety for elderly, polypharmacy patients, and prolonged use.

Recent Findings and Implications

• Efficacy Confirmation: Multiple Phase 3 trials reaffirm short-term efficacy in acute musculoskeletal pain.
• Safety Profile: Well-established, with common side effects being dry mouth, fatigue, and drowsiness. Long-term data remain limited but are expanding.
• Regulatory Feedback: Regulatory agencies emphasize need for further long-term safety data, especially regarding off-label use.

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Market Analysis

Current Market Landscape

Region	Market Share (%)	Leading Companies	Key Products	Pricing (per 30 tablets, USD)	Regulatory Status
North America	55%	Mallinckrodt, Teva, Mylan	Generic formulations, branded versions	$5 - $15	FDA-approved; generics dominate
Europe	25%	Sandoz, Stada, Pfizer	Generic and off-label options	€4 - €12	EMA approvals; off-label use common
Asia-Pacific	10%	Local generics producers	Generic formulations	$2 - $8	Varying regulatory approval status
ROW (Rest of World)	10%	Local and emerging markets players	Basic generics	Variable	Limited approvals, high off-label use

Market Drivers

• Prevalence of Musculoskeletal Conditions: Chronic back pain affects approximately 8-12% of the global population (WHO).
• Short-term Pain Management: Providers prefer Cyclobenzaprine for acute muscle spasms, with a typical prescription duration of 2-3 weeks.
• Generic Availability: Patent expiry in multiple markets has increased accessibility and cost competitiveness.
• Combination Therapy Trends: Growing use of Cyclobenzaprine as part of multimodal pain management.

Market Challenges

• Side Effect Profile: Drowsiness and anticholinergic effects may limit use in certain populations.
• Regulatory Scrutiny: Emphasis on opioid-sparing strategies reduces reliance on adjunct therapies, though Cyclobenzaprine remains favored for acute pain.
• Competition from Other Relaxants: Alternatives like methocarbamol, tizanidine, and botulinum toxin.

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Market Projection (2023-2028)

Forecast Assumptions

• Compound Annual Growth Rate (CAGR): 3.8%
• Factors Supporting Growth:
  • Increasing incidence of musculoskeletal injuries and chronic conditions.
  • Expanded clinical indications based on ongoing trial results.
  • Greater adoption of combination therapies and off-label uses.

Projected Market Values (USD Millions)

Year	Market Value	Growth Rate (%)
2023	820	—
2024	855	4.3
2025	895	4.7
2026	935	4.5
2027	975	4.3
2028	1015	4.2

Source: Market Research Future, Recent Analyst Reports (2022-2023)

Key Market Segments

• By Indication: Acute pain (largest), off-label chronic pain, combination therapy.
• By Region: North America remains dominant, with steady growth in APAC driven by expanding healthcare infrastructure.
• By Formulation: Oral tablets (>90%), with limited injectable forms primarily for clinical use.

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Comparison with Competitors

Drug	Formulation	Indications	Market Share (%)	Advantages	Limitations
Cyclobenzaprine	Oral Tablets	Musculoskeletal Spasms	55	Well-studied, generic availability	Sedative effects, anticholinergic
Tizanidine	Oral	Spasticity, chronic pain	20	Shorter half-life, fewer side effects	Costlier, less proven in acute pain
Methocarbamol	Oral/Injectable	Acute musculoskeletal pain	15	Different mechanism of action	Less effective for some patients
Carisoprodol	Oral	Muscle spasms	10	Rapid onset	Abuse potential, regulatory restrictions

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FAQs

1. What new clinical indications are being explored for Cyclobenzaprine?

Current clinical trials are investigating its efficacy in chronic pain management, fibromyalgia, and potential off-label uses for sleep disturbances associated with musculoskeletal conditions. These trials aim to expand its approved indications and optimize dosing strategies.

2. How is the safety profile of Cyclobenzaprine evolving according to recent studies?

While the established safety profile remains consistent — with common adverse effects including dry mouth, drowsiness, and dizziness — recent long-term safety studies focus on elderly populations and polypharmacy patients. These studies aim to mitigate anticholinergic side effects and assess cognitive impacts.

3. What are the key regulatory developments impacting Cyclobenzaprine?

Regulatory agencies like the FDA and EMA continue to evaluate long-term safety data, especially for extended use beyond approved short-term therapy. No significant regulatory restrictions have been introduced recently, but there is increased scrutiny on off-label prescribing practices.

4. How does market competition influence the future of Cyclobenzaprine?

The emergence of alternative relaxants and non-pharmacological therapies exerts pressure on Cyclobenzaprine's market share. Generic competition also constrains pricing, emphasizing the need for differentiation via expanded indications or combination approaches.

5. What are the implications of patent expirations for Cyclobenzaprine?

Major patents for proprietary formulations have expired in key markets, leading to increased generic availability and price erosion. This shift benefits healthcare systems through cost savings but challenges manufacturers to innovate or diversify through new formulations and indications.

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Key Takeaways

• Clinical Development: Ongoing trials aim to expand Cyclobenzaprine’s indications, particularly in chronic pain and combination therapies, potentially broadening its therapeutic scope.
• Market Dynamics: Generics dominate, with North America leading in market share; growth is steady but faces competition from other relaxants and non-drug interventions.
• Forecast Outlook: Moderate CAGR of approximately 3.8% projected over five years, supported by increasing musculoskeletal disorder prevalence and expanded clinical research.
• Regulatory & Safety Considerations: Long-term safety data collection remains critical, especially in vulnerable populations; regulatory agencies maintain a cautious stance on off-label use.
• Strategic Recommendations: Companies should focus on clinical trial outcomes, clinical guideline integration, and potential label expansions to secure competitive advantage.

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Sources

[1] World Health Organization. (2022). Musculoskeletal Conditions. https://www.who.int
[2] Market Research Future. (2023). Global Skeletal Muscle Relaxant Market Analysis & Forecast.
[3] ClinicalTrials.gov. (2023). Ongoing Clinical Trials involving Cyclobenzaprine.
[4] FDA Labeling and Regulatory Documents. (2022). Cyclobenzaprine Hydrochloride.
[5] IBISWorld. (2023). Global Pain Management Market Report.