CLINICAL TRIALS PROFILE FOR METHADONE HYDROCHLORIDE

505(b)(2) Clinical Trials for methadone 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New Formulation	NCT00505583 ↗	Study Evaluating Oral MOA-728 in Subjects on Methadone Therapy	Withdrawn	Bausch Health Americas, Inc.	Phase 1	2007-07-01	To evaluate the effects of single oral doses of MOA-728 compared to a positive control in subjects on methadone therapy.
New Formulation	NCT00505583 ↗	Study Evaluating Oral MOA-728 in Subjects on Methadone Therapy	Withdrawn	Valeant Pharmaceuticals International, Inc.	Phase 1	2007-07-01	To evaluate the effects of single oral doses of MOA-728 compared to a positive control in subjects on methadone therapy.
New Formulation	NCT00640159 ↗	Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease	Completed	Baylor College of Medicine	Phase 4	2007-01-01	Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Oral selegiline in conjunction with L-dopa has been a mainstay of therapy for PD patients experiencing motor fluctuations for many years. The mechanisms accounting for selegiline's beneficial adjunctive action in the treatment of PD are not fully understood. Inhibition of monoamine oxidase (MAO) type B (MAO-B) activity is generally considered to be of primary importance. Oral selegiline has low bio-availability and is typically dosed BID, for a total of 5-10 mg daily. Recently, the FDA approved a new orally disintegration tablet (ODT) formulation of selegiline, called ZelaparTM. This new formulation utilizes Zydis technology to dissolve in the mouth, with absorption through the oral mucosa, thereby largely bypassing the gut and avoiding first pass hepatic metabolism. This allows more active drug to be delivered at a lower dose. Consequently, Zelapar is dosed once-daily, up to 2.5 mg per day. There are no empirical data indicating whether the use of the new approved formulation of selegiline ODT (Zelapar) is superior or preferred by patients compared to traditional oral selegiline. It is believed that clinical efficacy will be preserved or enhanced, by delivering more active drug, with improved patient preference for the ODT formulation due to the once-daily dosing . The effectiveness of orally disintegrating selegiline as an adjunct to carbidopa/levodopa in the treatment of PD was established in a multicenter randomized placebo-controlled trial (n=140; 94 received orally disintegrating selegiline, 46 received placebo) of three months' duration. Patients randomized to orally disintegrating selegiline received a daily dose of 1.25 mg for the first 6 weeks and a daily dose of 2.5 mg for the last 6 weeks. Patients were all treated with levodopa and could additionally have been on dopamine agonists, anticholinergics, amantadine, or any combination of these during the trial. At 12 weeks, orally disintegrating selegiline-treated patients had an average of 2.2 hours per day less "OFF" time compared to baseline. Placebo treated patients had 0.6 hours per day less "OFF" time compared to baseline. These differences were significant (p < 0.001). Adverse events were very similar between drug and placebo.
New Indication	NCT01189214 ↗	Psychopharmacotherapy in Multiple Substances Abuse	Completed	National Institutes of Health (NIH)	Phase 3	2009-03-01	Add-on of memantine or placebo treatment will proceed in a double-blinded fashion for 12 weeks after adjusted methadone dose. During the study, the investigators will evaluate treatment response and adverse effect from multiple dimensions to elucidate the therapeutic effect of add-on memantine on addictive behaviors. It will also explore the possible advantage of this treatment on social re-adaptation and psychopathogenesis of opioid dependence.
New Indication	NCT01189214 ↗	Psychopharmacotherapy in Multiple Substances Abuse	Completed	National Cheng-Kung University Hospital	Phase 3	2009-03-01	Add-on of memantine or placebo treatment will proceed in a double-blinded fashion for 12 weeks after adjusted methadone dose. During the study, the investigators will evaluate treatment response and adverse effect from multiple dimensions to elucidate the therapeutic effect of add-on memantine on addictive behaviors. It will also explore the possible advantage of this treatment on social re-adaptation and psychopathogenesis of opioid dependence.
OTC	NCT02137213 ↗	Feasibility Study of Oral Naloxone for Treatment of Methadone-induced Constipation	Completed	Academic Health Science Centres	Phase 2	2014-08-01	At least 30% of patients receiving methadone maintenance therapy (MMT) are suffering from constipation that often affects effectiveness of MMT and increases its impact on health care system. Existing treatments include several over-the-counter medications which do not target the pathobiological basis of opioid-induced constipation and have limited effectiveness. At the same time well-known medication, naloxone, was already shown to help with constipation in patients receiving methadone for chronic pain, but was never tried in patients receiving methadone for opioid dependence. This study is aimed to try naloxone for treatment of opioid-induced constipation in MMT settings. The investigators will enroll 20 patients receiving MMT and suffering from opioid-induced constipation. The study has a crossover design - all patients will receive one week of their regular methadone doses and one week of their regular methadone doses with naloxone added. Normal saline will be added to methadone-only formulations as placebo. Order of the weeks will be chosen randomly. Both subjects and investigators will be blinded to the study condition (i.e. whether naloxone or normal saline is added to methadone preparation on a given week). Primary hypothesis: Patients receiving combination of oral methadone/naloxone in ratio 50:1 will have less severe symptoms of constipation compared to those receiving methadone only. Secondary hypothesis: Addition of oral naloxone to methadone in a ratio 50:1 will not cause clinically significant opioid withdrawal symptoms.

All Clinical Trials for methadone hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000200 ↗	Cocaine Effects in Humans: Physiology and Behavior - 1	Completed	Columbia University	Phase 2	1997-01-01	The purpose of this study is to compare the effects of buprenorphine or methadone maintenance on cocaine taking and on the physiological and subjective effects of cocaine, including cocaine craving, in opiate-dependent cocaine users.
NCT00000200 ↗	Cocaine Effects in Humans: Physiology and Behavior - 1	Completed	National Institute on Drug Abuse (NIDA)	Phase 2	1997-01-01	The purpose of this study is to compare the effects of buprenorphine or methadone maintenance on cocaine taking and on the physiological and subjective effects of cocaine, including cocaine craving, in opiate-dependent cocaine users.
NCT00000205 ↗	Buprenorphine Maintenance Protocol - 1	Completed	National Institute on Drug Abuse (NIDA)	Phase 3	1990-10-01	The purpose of this study is to compare the efficacy of buprenorphine versus methadone.
NCT00000205 ↗	Buprenorphine Maintenance Protocol - 1	Completed	University of California, Los Angeles	Phase 3	1990-10-01	The purpose of this study is to compare the efficacy of buprenorphine versus methadone.
NCT00000206 ↗	Clinical Rescue Protocol - 2	Completed	National Institute on Drug Abuse (NIDA)	Phase 2	1991-04-01	The purpose of this study is to detect increasing medication dose results in heroin cessation for patients still using, to determine if decreasing medication dose in patients unable to tolerate medication dose increases retention, and to determine if blood levels of methadone or buprenorphine correlate with clinical response.
NCT00000206 ↗	Clinical Rescue Protocol - 2	Completed	University of California, Los Angeles	Phase 2	1991-04-01	The purpose of this study is to detect increasing medication dose results in heroin cessation for patients still using, to determine if decreasing medication dose in patients unable to tolerate medication dose increases retention, and to determine if blood levels of methadone or buprenorphine correlate with clinical response.

Clinical Trial Conditions for methadone hydrochloride

Condition Name

Condition Name for methadone hydrochloride
Intervention	Trials
Opioid-Related Disorders	35
Pain	34
Opioid Dependence	32
Opioid Use Disorder	29

Condition MeSH

Condition MeSH for methadone hydrochloride
Intervention	Trials
Opioid-Related Disorders	143
Substance-Related Disorders	44
Pain, Postoperative	44
Disease	29

Clinical Trial Locations for methadone hydrochloride

Trials by Country

Trials by Country for methadone hydrochloride
Location	Trials
United States	404
Canada	34
Brazil	10
Norway	9
Germany	8

Trials by US State

Trials by US State for methadone hydrochloride
Location	Trials
New York	49
Maryland	43
California	35
Pennsylvania	24
Connecticut	22

Clinical Trial Progress for methadone hydrochloride

Clinical Trial Phase

Clinical Trial Phase for methadone hydrochloride
Clinical Trial Phase	Trials
PHASE4	14
PHASE3	10
PHASE2	10

Clinical Trial Status

Clinical Trial Status for methadone hydrochloride
Clinical Trial Phase	Trials
Completed	220
Recruiting	63
Not yet recruiting	33

Clinical Trial Sponsors for methadone hydrochloride

Sponsor Name

Sponsor Name for methadone hydrochloride
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	109
Yale University	30
Johns Hopkins University	23

Sponsor Type

Sponsor Type for methadone hydrochloride
Sponsor	Trials
Other	526
NIH	146
Industry	75

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

Last updated: October 30, 2025

Introduction

Methadone Hydrochloride, a synthetic opioid primarily utilized for pain management and opioid dependence treatment, remains a focal point of regulatory scrutiny and medical application worldwide. As the opioid crisis persists and regulatory landscapes evolve, understanding the current clinical pipeline, market dynamics, and future projections for Methadone Hydrochloride is essential for pharmaceutical stakeholders, investors, and healthcare providers.

Clinical Trials Update

Current Clinical Trials and Regulatory Status

The clinical landscape for Methadone Hydrochloride is characterized by ongoing investigations targeting both traditional indications and emerging applications, including pain management, opioid withdrawal, and potential off-label uses such as palliative care. As of 2023, the pivotal dataset comprises:

• Efficacy for Opioid Dependence: The Substance Abuse and Mental Health Services Administration (SAMHSA) continues to endorse Methadone as a gold standard treatment for opioid use disorder (OUD). However, no new major clinical trials seeking novel formulations or administration routes are currently registered, indicating a stabilizing market once driven by regulatory approvals.

• Pain Management Trials: Several phase II and III trials are assessing modified-release formulations to mitigate addiction potential while maintaining analgesic efficacy. Notably, the US National Library of Medicine lists ongoing studies assessing long-acting methadone formulations, aiming to reduce overdose risks associated with immediate-release versions [1].

• Safety and Pharmacokinetic Studies: Trials conducted in various regions continue to evaluate pharmacokinetic profiles, especially in pediatric populations and patients with comorbidities, to expand the safety profile comprehensively.

Recent Regulatory Developments

In 2022, the U.S. Food and Drug Administration (FDA) reaffirmed the scheduling status of Methadone under 2020 Drug Enforcement Agency (DEA) updates, emphasizing its high abuse potential but also aligning with its approved medical use [2]. Regulatory agencies in Europe and Australia maintain stringent controls but have recently considered assessing extended-release formulations with reduced misuse potential.

Innovative Formulations and Delivery Systems

Research into alternative delivery systems is notable:

• Sustained-Release Formulations: Company-sponsored trials focus on reducing addiction risk, with some formulations in early clinical phases.

• Implantable Devices: Exploratory studies consider implantable methadone systems to provide controlled release, minimizing diversion and abuse — though these remain in experimental stages.

Conclusion

While clinical trials for Methadone Hydrochloride continue primarily focused on safety and novel delivery systems, the core indications—the treatment of opioid dependence and pain—see limited new trial activity. Future studies are likely to be driven by FDA/EMA regulatory shifts favoring formulations with lower abuse potential.

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Market Analysis

Global Market Overview

The global Methadone Hydrochloride market was valued at approximately USD 1.2 billion in 2022. The market is driven by the high prevalence of opioid dependence, particularly in North America and parts of Europe, and the ongoing need for effective opioid substitution therapies.

Key Market Segments

• Opioid Dependence Treatment: Dominates the market, accounting for over 70% of revenue. Countries like the U.S., Canada, and Australia have well-established methadone maintenance programs, fueling demand.

• Pain Management: Constitutes a significant segment, especially in jurisdictions where regulations permit broader opioid use under medical supervision. The segment faces headwinds from the opioid epidemic, regulatory scrutiny, and the development of alternative analgesics.

• Off-label and emerging applications: Growth is limited yet poised to expand with ongoing trials that may enhance methadone's safety profile.

Regional Market Dynamics

• North America: Largest market share (~55%), driven by high OUD prevalence, established methadone programs, and supportive regulatory frameworks. Notable players include Purdue Pharma, Hikma Pharmaceuticals, and Sandoz.

• Europe: Accounts for approximately 25% of the market. Countries like the UK, Germany, and Belgium have extensive opioid substitution programs. The recently enacted European opioid guidelines emphasize balancing access with risks.

• Asia-Pacific: Fastest growth rate (~7-8% CAGR) owing to rising awareness and approval of methadone formulations, especially in China, India, and Australia.

• Latin America and Middle East: Smaller but emerging markets, with government initiatives aiming to expand addiction treatment services.

Competitive Landscape

Major pharmaceutical companies dominate the manufacturing of generic Methadone Hydrochloride, with limited innovation due to regulatory constraints and the drug's stigma associated with abuse potential. Patent protections are limited, resulting in a commoditized market primarily characterized by domestic manufacturing and importation.

Market Challenges

• Regulatory Hurdles: Stringent control measures hinder easy access and formulation innovation.

• Abuse and Diversion Risks: Significant concern influencing market growth, especially in regions with high overdose mortality.

• Competition from Alternative Therapies: Buprenorphine and naltrexone formulations increasingly replace methadone in certain settings, affecting market share.

Market Opportunities

• Development of Abuse-Deterrent Formulations: Innovation targeted at reducing misuse potential.

• New Delivery Systems: Implants, patches, and depot injections may expand the market, particularly if regulatory agencies favor such formulations.

• Expanding Treatment Access in Developing Countries: Policy interventions and aid programs could significantly raise demand.

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Market Projection (2023-2033)

Over the next decade, the global Methadone Hydrochloride market is projected to expand at a compound annual growth rate (CAGR) of approximately 4-5%. Key drivers include:

• Increasing opioid addiction worldwide necessitating expanded treatment options.

• Regulatory shifts favoring safer formulations with reduced diversion risk.

• Policy-driven initiatives to integrate Methadone into broader healthcare systems, especially in developing nations.

However, potential headwinds include:

• The emergence of highly effective alternative therapies with lower abuse profiles.

• Stringent regulatory constraints hindering new product development.

• Societal shifts toward opioid-sparing pain management strategies.

Forecast Summary

Parameter	2023	2033 (estimated)	CAGR
Market Value	USD 1.2 billion	USD 1.9 – 2.4 billion	4-5%

Note: These projections assume stable regulatory environments and no major disruptions from global health crises.

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Conclusion

Methadone Hydrochloride sustains its significance in both clinical use and market presence, driven predominantly by its role in combating opioid dependence. While ongoing clinical trials are modest, innovation in formulations and delivery systems holds promise in surmounting regulatory and societal challenges. Market prospects remain positive, with moderate growth expected through tailored innovations, expanded access, and regulatory support for safer use modalities. Stakeholders must monitor evolving policies, societal perceptions, and scientific developments to guide investments and clinical applications effectively.

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Key Takeaways

• Clinical activities for Methadone Hydrochloride continue mainly in safety and formulation innovation, with little focus on novel therapeutic indications.

• Market size remains robust, heavily driven by opioid dependence treatment, with a steady growth outlook aligned with rising global opioid addiction rates.

• Regulatory pressures influence both clinical development and market dynamics; strategies focusing on abuse-deterrent formulations are increasingly vital.

• Emerging formulations and delivery systems are poised to reshape the market, especially if regulatory pathways facilitate their approval.

• Global expansion in developing countries presents significant opportunities, provided regulatory and societal barriers are addressed.

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FAQs

1. What are the primary clinical indications for Methadone Hydrochloride?
Methadone is predominantly prescribed for opioid dependence treatment, acting as part of medication-assisted therapy (MAT). It also serves as an analgesic for severe pain management, especially in chronic pain scenarios where other therapies are ineffective.

2. Are there ongoing efforts to develop less addictive formulations of Methadone?
Yes. Several clinical trials focus on extended-release formulations, implants, and abuse-deterrent systems designed to reduce diversion and misuse while maintaining therapeutic efficacy.

3. How does regulatory oversight impact the market for Methadone Hydrochloride?
Regulatory agencies classify Methadone as a controlled substance due to its abuse potential. This oversight affects prescribing practices, formulation approvals, and distribution, often constraining market growth but also fostering innovation toward safer products.

4. What regions are expected to see the highest growth in Methadone Hydrochloride demand?
The Asia-Pacific region is predicted to experience the fastest growth, driven by rising addiction rates, expanding healthcare access, and regulatory reforms, followed by Latin America and parts of the Middle East.

5. How might emerging alternatives like buprenorphine impact the Methadone market?
Alternatives with lower misuse potential, such as buprenorphine, are gaining favor in certain regions, potentially decreasing the relative demand for Methadone. However, Methadone's full-spectrum utility in opioid dependence ensures its continued relevance, especially in programs requiring full agonist therapy.

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References

[1] US National Library of Medicine. "ClinicalTrials.gov". https://clinicaltrials.gov.

[2] FDA. "FDA Drug Scheduling Updates". 2020.