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.
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.

Clinical Trial Conditions for CYCLOBENZAPRINE HYDROCHLORIDE

Condition Name

Condition Name for CYCLOBENZAPRINE HYDROCHLORIDE
Intervention	Trials
Primary Fibromyalgia	4
PTSD	4
Healthy Adults	4
Healthy	3

Condition MeSH

Condition MeSH for CYCLOBENZAPRINE HYDROCHLORIDE
Intervention	Trials
Myofascial Pain Syndromes	9
Fibromyalgia	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
Florida	7
New York	7
Washington	7
Massachusetts	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
Neurana Pharmaceuticals, Inc.	2
Eurofarma Laboratorios S.A.	2

Sponsor Type

Sponsor Type for CYCLOBENZAPRINE HYDROCHLORIDE
Sponsor	Trials
Industry	34
Other	20
FED	1

Cyclobenzaprine Hydrochloride: Clinical Trials Update and Market Analysis With Projections

Last updated: April 28, 2026

Cyclobenzaprine hydrochloride is an oral, centrally acting skeletal muscle relaxant approved in the U.S. for short-term relief of muscle spasm associated with acute, painful musculoskeletal conditions. The product is established and widely generic. Public clinical-trial activity remains sparse and is dominated by bioequivalence, formulation, or secondary indications rather than new registrational-phase outcomes.

What is the current clinical-trials footprint for cyclobenzaprine hydrochloride?

Global registrations and active-study signal

Public trial registries show ongoing and recurring studies, but the dominant pattern for cyclobenzaprine is late-stage development is not the center of gravity. Study types concentrate on:

• Bioequivalence and pharmacokinetics for generic products and reformulations
• Real-world observational cohorts and safety monitoring
• Targeted efficacy comparisons as adjunct therapy in acute musculoskeletal pain contexts

What phases are most represented?

Across the ongoing publicly visible studies, the practical signal is late-stage execution rather than a pipeline build:

• Phase 1 studies appear primarily for PK/bioequivalence
• Phase 2/3 are less frequent in the public record relative to bioequivalence and PK work
• Phase 4 studies show up as safety or comparative effectiveness studies when sponsors pursue post-approval evidence generation

Trial design patterns seen in published registry entries

The recurring design elements are:

• Single-dose or steady-state PK endpoints
• Muscle spasm pain scales as secondary endpoints, often as comparative tools rather than primary registrational endpoints
• Safety endpoints concentrated on CNS adverse events and anticholinergic effects consistent with class labeling

Clinical-trial update summary (actionable read)

• No dominant, registrational Phase 3 “replacement” pathway is visible from public-trial patterns.
• Competitive differentiation is largely product-level (bioequivalence, formulation, dosing convenience) rather than mechanism-level innovation.
• For investors or R&D leads, the main clinical relevance is regulatory defensibility of generics and incremental evidence that supports labeling maintenance rather than expansion.

How big is the cyclobenzaprine market, and what drives volume?

Market structure

Cyclobenzaprine is a mature, prescription-driven therapy with a large generic base in the U.S. Key structural features:

• Multiple generic entrants compress net pricing.
• Utilization clusters around short-term musculoskeletal pain visits in primary care, urgent care, and outpatient settings.
• Prescribing is sensitive to guideline positioning of muscle relaxants and to payer formularies.

Demand drivers

The market expands or contracts based on:

• Acute musculoskeletal episode incidence (sprains, strains, back pain)
• Prescriber switching between muscle relaxants in response to tolerability or coverage rules
• Generic pricing dynamics that determine channel mix and formulary status

Supply and competitive pressure

Generic competition drives:

• Lower realized prices over time
• Increased focus on bioequivalence compliance and launch speed
• Higher emphasis on distribution agreements and pharmacy network placement

What are projections for cyclobenzaprine sales through the next 5 years?

Projection framework

Given maturity, high generic penetration, and limited registrational-phase expansion, projections typically follow:

• Low-to-mid single-digit volume growth (driven by underlying acute musculoskeletal treatment rates)
• Ongoing price erosion (generic competition and payer pressure)
• Net sales growth that tracks inflation-adjusted demand only weakly

Base-case projection (directional)

The near-term expectation is:

• Volume: modest growth
• Net revenue: flat to modest decline in many markets due to pricing pressure
• U.S. channel: continued dominance of generics with periodic pricing resets after new entrants

Outcome: what to assume in modeling

A practical five-year model for cyclobenzaprine should assume:

• Stable prescription volume
• Continued price erosion
• Minimal incremental market expansion from new indications, unless a major guideline or label change occurs

What does the IP and development landscape imply for future commercialization?

Commercial reality

For a mature, widely generic molecule, commercialization economics usually depend on:

• Regulatory execution (bioequivalence and ANDA readiness)
• Formulation and dosing differentiation only if supported by regulatory pathways and payer preference
• Manufacturing scale and cost-of-goods discipline

Investment implication

The highest-return opportunities typically sit in:

• Fast follow generic launches where regulatory risk is low
• Line extensions if a distinguishable regulatory path exists (for example, distinct release characteristics supported by evidence)
• Evidence-generation for formulary retention (real-world tolerability data and adherence)

Clinical development options: where can sponsors still find value?

1) Bioequivalence and PK modernization

Sustained trial activity in PK/BE supports:

• Continued pipeline for generic product approvals
• Ongoing re-entries when manufacturing sites or formulations change

2) Comparative effectiveness and safety data

Post-approval studies can help:

• Support payer and formulary positioning
• Reduce prior authorization friction if tolerability is favorable relative to alternatives

3) Label maintenance evidence

Large, slow-moving evidence generation supports continued market access, particularly where payer policy depends on documentation.

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Market and Regulatory Anchors (U.S.)

Cyclobenzaprine hydrochloride is an established prescription product with regulatory status governed by U.S. drug approval and labeling. The reference labeling describes use for acute musculoskeletal conditions and includes class-consistent CNS and anticholinergic safety considerations. (FDA labeling and approval history are the core anchors for clinical endpoint expectations and safety monitoring.) [1]

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Key Takeaways

• Cyclobenzaprine is a mature prescription muscle relaxant with active but mostly non-registrational public clinical-trial patterns (bioequivalence, PK, observational and comparative work).
• Market growth is constrained by generic competition; projections follow modest volume offset by price erosion, driving net sales to be flat to modestly down in many scenarios.
• Commercial differentiation is mainly product-level execution (regulatory speed, formulation, distribution) rather than new mechanism breakthroughs.
• Future opportunities concentrate in fast generic launches, formulary-retention evidence, and post-approval safety/comparative data aligned to payer needs.

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FAQs

1) Is there evidence of a new registrational Phase 3 development push for cyclobenzaprine?

Public trial activity is skewed toward bioequivalence, PK, and secondary evidence generation rather than clear registrational-phase dominance. [2]

2) What trial endpoints dominate cyclobenzaprine studies?

Endpoints typically center on pharmacokinetics/bioequivalence; where efficacy is measured, muscle spasm or pain scales appear largely as comparative or secondary endpoints. [2]

3) What are the main competitive risks in the cyclobenzaprine market?

The primary risk is persistent generic pricing pressure and payer-driven formulary shifts among muscle relaxants. [1][3]

4) What drives prescribing in the real world?

Prescribing tracks acute musculoskeletal episode treatment patterns and formulary coverage, with switching across muscle relaxants based on tolerability and access. [3]

5) Where can sponsors still create commercial value?

Value typically comes from regulatory execution (bioequivalence readiness, manufacturing scale) and evidence supporting formulary retention, not from mechanism-driven pipeline breakthroughs. [1][2]

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References

[1] U.S. Food and Drug Administration. (n.d.). Drug label information for cyclobenzaprine hydrochloride. FDA. https://www.accessdata.fda.gov
[2] U.S. National Library of Medicine. (n.d.). ClinicalTrials.gov results for cyclobenzaprine hydrochloride. ClinicalTrials.gov. https://clinicaltrials.gov
[3] IQVIA Institute / industry reporting (general market context for mature generic oral products). (n.d.). Prescription and generic market dynamics for established therapies. IQVIA. https://www.iqvia.com