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
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, Market Analysis, and Generic Entry Projection

Last updated: July 28, 2026

Cyclobenzaprine hydrochloride is an off-patent, long-established, centrally acting muscle relaxant with broad generic availability in the US and multiple markets. Because the product is not protected by meaningful near-term exclusivity typical of newer drugs, the key forward-looking variable is not pipeline differentiation but ongoing generic competition, formulation substitutes (extended-release and combination products where applicable), and price compression.

What is the current clinical development status of cyclobenzaprine hydrochloride?

Answer: There is no widely recognized, late-stage (Phase 3/registration) development program that meaningfully changes the competitive landscape for cyclobenzaprine hydrochloride in major geographies, and the practical “clinical update” in 2025-2026 is largely composed of smaller studies, labeling or use-refinement efforts, and academic trials rather than new product approvals.

Are any Phase 3 or pivotal trials ongoing for cyclobenzaprine?

Answer: No ongoing, registration-defining Phase 3 program is clearly documented as a driver of new regulatory outcomes.

What typically appears in the evidence base

• Post-marketing observational studies and outcomes research (pain, disability, work function).
• Comparative studies of cyclobenzaprine versus other muscle relaxants or nonpharmacologic approaches.
• Studies focused on tolerability, sedation, dose timing, and elderly safety.
• Trials examining sleep-related endpoints or adjunct use with NSAIDs or physical therapy.

What have recent trials focused on?

Answer: Recent work concentrates on real-world effectiveness and safety signals rather than new mechanisms:

• Sedation and impairment risk (especially in older adults).
• Head-to-head comparisons with other muscle relaxants (efficacy and adverse event profiles).
• Functional outcomes in acute low back pain and musculoskeletal spasm.
• Use patterns and persistence (how long patients continue therapy).

Which clinical trials are most relevant for cyclobenzaprine positioning in 2025-2026?

Answer: Trials that inform prescribing behavior and payer coverage tend to focus on safety and tolerability, dosing strategy, and comparative effectiveness, not new endpoints that would support a distinct regulatory pathway.

What endpoints drive formulary decisions?

Common endpoints used in newer studies:

• Pain intensity (often numeric rating scales).
• Functional outcomes (range of motion, disability scales).
• Time to meaningful improvement.
• Adverse events, discontinuation rates, and sedation-related outcomes.

How do safety results affect real-world use?

Key risk themes that drive labeling adherence and patient selection:

• CNS depression and next-day impairment risk.
• Higher adverse event rates in older populations.
• Drug-drug interaction potential through CNS-active pathways.

What is the market size and demand outlook for cyclobenzaprine hydrochloride?

Answer: Demand remains stable to declining in many markets due to long-term generic penetration and therapeutic substitution, with volume supported by the drug’s established indication base (acute musculoskeletal pain/spasm).

How does generic penetration shape revenue?

Generic entry compresses net pricing quickly, while volumes usually persist:

• Brand erosion after generic launches.
• Low margin aftermarket dynamics for oral tablets.
• Proliferation of package size and manufacturer-led pricing competition.

What product formats hold market share?

Cyclobenzaprine’s market footprint typically depends on:

• Immediate-release oral tablets (most common).
• Extended-release versions in markets where approved (these can preserve share longer due to dosing convenience narratives).
• Local formulation differences and substitution rules at pharmacy level.

How do prices and margins trend for cyclobenzaprine generics?

Answer: Prices trend downward with each incremental generic manufacturer and with periodic marketwide rebate and wholesaler-channel adjustments.

What to expect commercially

• Early generic entrants capture volume quickly but face margin erosion as additional ANDAs launch.
• Larger generic manufacturers can maintain share through supply reliability and contracting.
• Smaller brands compete through pricing and distribution reach.

When does cyclobenzaprine lose exclusivity, and what does that mean for market supply?

Answer: Cyclobenzaprine hydrochloride is effectively off exclusivity. The competitive impact is not a single “cliff” event but ongoing generic saturation that keeps driving price pressure.

What is the practical exclusivity timeline for cyclobenzaprine?

• With no meaningful remaining product exclusivity for the molecule, supply expansion continues through generic ANDAs and distribution optimization.
• Any remaining differentiation typically comes from specific formulation variants rather than the base API.

What is the Orange Book status of cyclobenzaprine hydrochloride?

Answer: Cyclobenzaprine hydrochloride is widely represented as an established generic with multiple ANDAs and entries reflecting formulation and process claims where applicable, but the base drug does not show near-term, high-impact exclusivity at the molecule level.

How to interpret Orange Book listings for an off-patent drug

For older oral drugs, Orange Book “strength” is usually limited by:

• Old composition-of-matter expirations.
• Many remaining patents being formulation-specific or method-limited.
• Low probability of blocking generic competition absent a still-active, broadly enforced claim set.

What patents protect cyclobenzaprine hydrochloride, and how strong is the patent estate?

Answer: The patent estate for cyclobenzaprine hydrochloride is generally not expected to create meaningful barriers for generic supply in the medium term because the molecule and most core claims are already expired or non-obstructive.

What types of patents remain most likely to matter?

Where still present, residual claims tend to fall into:

• Formulation or release profile claims for specific dosage strengths or extended-release designs.
• Manufacturing process claims that can be worked around through alternative process routes.
• Method-of-use claims are less common for older, well-established symptom-based indications.

How does patent strength translate to generic risk?

For investors and licensing teams, the key point is:

• “Patent estate” value is usually low for the base molecule at this stage.
• Any enforceable residue is likely to be narrow and tied to a specific product variant, not the class.

Are there any Paragraph IV challenges or recent generic litigation involving cyclobenzaprine?

Answer: No consistent stream of high-profile, ongoing Paragraph IV disputes is a known driver for the cyclobenzaprine competitive landscape.

What would a Paragraph IV mean here?

For an off-patent drug:

• The economics are usually shaped by supply and pricing, not by long litigation outcomes.
• Settlements, if they occur, tend to accelerate launches rather than delay them for extended periods.

How does cyclobenzaprine compare with other muscle relaxants on efficacy and safety?

Answer: Cyclobenzaprine is a common comparator within the muscle relaxant class. Real-world prescribing typically reflects tolerability and sedation risk, especially versus agents with different CNS profiles.

Where do clinicians see cyclobenzaprine fit?

Common positioning:

• Short-term adjunct for acute musculoskeletal conditions.
• Use when a provider prefers a known efficacy and dosing profile.
• Avoidance or caution in older patients and those with high sedation risk.

What are the practical prescribing differentiators?

• Sedation burden and next-day impairment considerations.
• Dosing convenience for extended-release options (where available).
• Patient selection based on comorbidities and concomitant sedatives.

What generic entry risks exist for cyclobenzaprine hydrochloride?

Answer: Entry risks are low in the sense of molecule-level patent blocking. The dominant risks are commercial, not legal: price wars, margin compression, supply chain execution, and payer contracting.

What are the main execution risks for new generic supply?

• API and excipient sourcing reliability.
• Manufacturing compliance and batch release timing.
• Stability and bioequivalence performance for specific formulations.
• Channel access and contracting speed.

Market projection: What is the 3-to-5-year outlook for cyclobenzaprine sales?

Answer: The outlook is for continued low-single-digit growth or stable volume with ongoing price compression in many markets, with revenue more likely to track volume than to expand meaningfully on price.

Base-case projection logic

• Stable diagnosis frequency for acute musculoskeletal pain syndromes.
• Persistent generic availability keeps volume supported.
• Each new generic entrant typically pushes pricing down.
• Extended-release variants may hold relative value versus immediate-release, depending on local formulary preference.

Scenario table (commercial, not legal)

Scenario	Drivers	Expected outcome (3-5 years)
Stable revenue	Limited incremental entrant capacity, contract stability	Flat-to-low growth driven by volume
Revenue decline	Continued entrants and price competition	Downward net price pressure dominates
Mild resilience	Stronger uptake of extended-release or pharmacy preference	Slightly better revenue than base case

Which companies are most exposed to cyclobenzaprine pricing pressure?

Answer: Brand incumbents and smaller generic brands are most exposed to net price erosion. Large multi-product generics are better positioned to absorb margin pressure through scale and contracting.

Where are the concentration points?

• Wholesaler distribution and national formulary penetration determine share durability.
• Contracting cycles can shift share quickly among manufacturers.

Key Takeaways

• Cyclobenzaprine hydrochloride is off meaningful exclusivity, with competition dominated by generics rather than patent-driven launches.
• Clinical “updates” in the near term are expected to be incremental, focused on safety, comparative effectiveness, and real-world outcomes rather than pivotal registration milestones.
• Market outlook in 3-5 years is driven by generic pricing dynamics: volume likely holds, revenue likely compresses, and any relative protection comes from formulation convenience or formulary position.
• Legal risk for new generic entry is low at the molecule level, while commercial execution risk remains the primary constraint.

FAQs

1. Is cyclobenzaprine still prescribed as a first-line muscle relaxant in acute low back pain?
2. Do extended-release cyclobenzaprine products face different regulatory or formulation constraints than immediate-release?
3. What patient populations are highest risk for cyclobenzaprine sedation or impairment?
4. How quickly do net prices typically decline after additional generic entrants for older oral muscle relaxants?
5. Are there any formulation-specific patents that can delay a particular cyclobenzaprine generic product launch?

References

1. U.S. Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA website.
2. ClinicalTrials.gov. Cyclobenzaprine hydrochloride studies search results. National Library of Medicine.
3. PubMed. Publications on cyclobenzaprine randomized trials and observational safety studies.