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
Healthy Adults	4
Primary Fibromyalgia	4
PTSD	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	129
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
Ohio	6

Clinical Trial Progress for Cyclobenzaprine Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Cyclobenzaprine Hydrochloride
Clinical Trial Phase	Trials
Phase 4	6
Phase 3	15
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Cyclobenzaprine Hydrochloride
Clinical Trial Phase	Trials
Completed	25
Terminated	8
Not yet recruiting	2

Clinical Trial Sponsors for Cyclobenzaprine Hydrochloride

Sponsor Name

Sponsor Name for Cyclobenzaprine Hydrochloride
Sponsor	Trials
Tonix Pharmaceuticals, Inc.	15
Neurana Pharmaceuticals, Inc.	2
Eurofarma Laboratorios S.A.	2

Sponsor Type

Sponsor Type for Cyclobenzaprine Hydrochloride
Sponsor	Trials
Industry	33
Other	15
U.S. Fed	1

Cyclobenzaprine Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction to Cyclobenzaprine Hydrochloride

Cyclobenzaprine hydrochloride is a muscle relaxant used to treat muscle spasms and pain associated with various musculoskeletal conditions, including fibromyalgia. The drug has been in the spotlight recently due to significant advancements in its clinical trials and market projections.

Clinical Trials Update

Phase 3 RESILIENT Trial

One of the most notable updates comes from the Phase 3 RESILIENT trial conducted by Tonix Pharmaceuticals. This trial evaluated the efficacy and safety of TNX-102 SL, a sublingual formulation of cyclobenzaprine hydrochloride, for the management of fibromyalgia.

• Primary Endpoint: The trial met its primary endpoint, showing a statistically significant reduction in daily pain severity scores compared to placebo. The least squares mean difference was -0.7 units (p = 0.00005)[1][4][5].
• Secondary Endpoints: The trial also met all key secondary endpoints, including significant improvements in sleep quality, fatigue, and overall fibromyalgia symptoms and function based on the Fibromyalgia Impact Questionnaire – Revised (FIQ-R)[1][4].
• Rapid Onset of Action: The treatment showed a rapid onset of action, with separation from placebo observed at week 1 and sustained across all 14 weeks of the study[1][4].

Clinical Pharmacokinetic Bridging Study

In addition to the RESILIENT trial, Tonix Pharmaceuticals conducted a clinical pharmacokinetic bridging study to support the development and regulatory filings of TNX-102 SL (Tonmya) in Japan and China. This study indicated that the pharmacokinetic parameters of cyclobenzaprine were comparable in ethnic Japanese and Chinese volunteers to Caucasian volunteers, supporting the potential for approval and marketing in these regions[5].

Market Analysis

Global Market Growth

The global cyclobenzaprine market is anticipated to grow at a significant Compound Annual Growth Rate (CAGR) of 4.2% during the forecast period. This growth is driven by the high prevalence of chronic pain conditions such as low back pain, osteoarthritis, and fibromyalgia[2].

Market Segments

• Relieve Muscle Spasms: The segment for relieving muscle spasms holds a prominent share in the global cyclobenzaprine market. Cyclobenzaprine is widely used to treat muscle spasms caused by acute, painful musculoskeletal problems[2].
• Fibromyalgia Treatment: The drug is also gaining traction for the treatment of fibromyalgia, as evidenced by the positive results from the RESILIENT trial[1][4].

Regional Outlook

• Asia-Pacific: This region is expected to hold a significant share in the market and is anticipated to grow the fastest during the forecast period. Factors contributing to this growth include the expansion of the geriatric population, rising disposable income, and increasing healthcare expenditure in countries like India and China[2].
• North America and Europe: These regions also hold substantial market shares, driven by the high prevalence of chronic pain conditions and the availability of advanced healthcare facilities[2].

Market Projections

Future Growth Drivers

• Increasing Prevalence of Chronic Pain: The rising prevalence of chronic pain conditions among adults, particularly those aged 60 and older, is expected to drive the demand for cyclobenzaprine[2].
• COVID-19 Pandemic Impact: The pandemic has led to an increase in back and neck discomfort due to changes in work habits, such as working from home, which has further boosted the demand for cyclobenzaprine[2].

Regulatory Filings

Tonix Pharmaceuticals plans to submit a New Drug Application (NDA) to the U.S. FDA for the approval of TNX-102 SL for the management of fibromyalgia in the second half of 2024. The company also intends to file regulatory applications in Japan and China based on the positive results from the clinical pharmacokinetic bridging study[1][4][5].

Competitive Landscape

The global cyclobenzaprine market is competitive, with several key players involved in the development and marketing of cyclobenzaprine products. Tonix Pharmaceuticals is a significant player, particularly with its innovative sublingual formulation, TNX-102 SL, which has shown promising results in clinical trials[1][4].

Adverse Events and Safety Profile

The clinical trials have shown that TNX-102 SL is generally well-tolerated, with an adverse event profile comparable to prior studies. Common adverse events include oral hypoesthesia, abnormal taste, oral paresthesia, tongue discomfort, somnolence, and headache[1][4].

Key Takeaways

• Clinical Trials Success: The Phase 3 RESILIENT trial demonstrated statistically significant and clinically meaningful reductions in daily pain and improvements in sleep quality, fatigue, and overall fibromyalgia symptoms.
• Market Growth: The global cyclobenzaprine market is expected to grow at a CAGR of 4.2%, driven by the increasing prevalence of chronic pain conditions.
• Regional Expansion: The Asia-Pacific region is anticipated to hold a significant market share and grow the fastest during the forecast period.
• Regulatory Filings: Tonix Pharmaceuticals plans to submit an NDA to the U.S. FDA and file regulatory applications in Japan and China.

FAQs

What is the primary use of cyclobenzaprine hydrochloride?

Cyclobenzaprine hydrochloride is primarily used to treat muscle spasms and pain associated with various musculoskeletal conditions, including fibromyalgia.

What were the key findings of the Phase 3 RESILIENT trial?

The Phase 3 RESILIENT trial showed a statistically significant reduction in daily pain severity scores and improvements in sleep quality, fatigue, and overall fibromyalgia symptoms compared to placebo.

Which regions are expected to drive the growth of the cyclobenzaprine market?

The Asia-Pacific region, followed by North America and Europe, is expected to drive the growth of the cyclobenzaprine market due to factors such as the expansion of the geriatric population and increasing healthcare expenditure.

What is the expected CAGR of the global cyclobenzaprine market?

The global cyclobenzaprine market is anticipated to grow at a CAGR of 4.2% during the forecast period.

When is Tonix Pharmaceuticals planning to submit an NDA for TNX-102 SL?

Tonix Pharmaceuticals plans to submit an NDA to the U.S. FDA for the approval of TNX-102 SL in the second half of 2024.

Sources

1. eMPR.com: Sublingual Cyclobenzaprine Reduces Pain in Patients with Fibromyalgia.
2. OMR Global: Cyclobenzaprine Market Share, Trends, Growth | Analysis and Forecast.
3. Cognitive Market Research: Cyclobenzaprine Drug Market Report 2024 (Global Edition).
4. BioSpace: 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.
5. Tonix Pharmaceuticals: Press Releases - Tonix Pharmaceuticals Holding Corp. (TNXP).