CLINICAL TRIALS PROFILE FOR HYDROCODONE

505(b)(2) Clinical Trials for HYDROCODONE

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
OTC	NCT02929589 ↗	Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy	Suspended	Mike O'Callaghan Federal Hospital	Phase 3	2018-07-05	This is a prospective, randomized, double-blinded, and placebo-controlled trial comparing oxycodone/acetaminophen prescribed with or without ibuprofen for pain control following open unilateral inguinal hernia repair, with allowed exception of any currently prescribed opioid (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, transdermal fentanyl), which can be continued. The patients will not be allowed to continue any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the investigators during this study. Patients not receiving Ibuprofen will be given a placebo pill composed of corn starch. The placebo pill will be formulated into the same shape, size and color as the ibuprofen capsule. Neither the investigators nor the research subjects will know if the subject is receiving a placebo versus Ibuprofen. The subjects will complete pain level and medication diaries, and will be followed for 2 months after their surgery. The research aims to discover the appropriate amount of opioid medication to prescribe to patients undergoing an elective open inguinal hernia repair, and reduce the total opioid dose needed by utilizing ibuprofen in combination. The investigators expect that the subjects who take ibuprofen will use less oxycodone/acetaminophen, and have comparable or lower mean pain levels. This could contribute to reducing the surplus opioids prescribed by physicians after surgery, which can lead to opioid use disorders. This particular procedure is common in men, and the findings have the potential to decrease the symptoms and pain of Active Duty members and DoD beneficiaries who undergo an inguinal hernia repair, and are at risk for prescription drug abuse or dependence.
OTC	NCT02929589 ↗	Ibuprofen to Decrease Opioid Use and Post-operative Pain Following Unilateral Inguinal Herniorrhaphy	Suspended	Mike O'Callaghan Military Hospital	Phase 3	2018-07-05	This is a prospective, randomized, double-blinded, and placebo-controlled trial comparing oxycodone/acetaminophen prescribed with or without ibuprofen for pain control following open unilateral inguinal hernia repair, with allowed exception of any currently prescribed opioid (codeine, hydrocodone, hydromorphone, morphine, methadone, oxymorphone, transdermal fentanyl), which can be continued. The patients will not be allowed to continue any over-the-counter pain medications, such as ibuprofen, naproxen, or acetaminophen containing medications, that were not prescribed by the investigators during this study. Patients not receiving Ibuprofen will be given a placebo pill composed of corn starch. The placebo pill will be formulated into the same shape, size and color as the ibuprofen capsule. Neither the investigators nor the research subjects will know if the subject is receiving a placebo versus Ibuprofen. The subjects will complete pain level and medication diaries, and will be followed for 2 months after their surgery. The research aims to discover the appropriate amount of opioid medication to prescribe to patients undergoing an elective open inguinal hernia repair, and reduce the total opioid dose needed by utilizing ibuprofen in combination. The investigators expect that the subjects who take ibuprofen will use less oxycodone/acetaminophen, and have comparable or lower mean pain levels. This could contribute to reducing the surplus opioids prescribed by physicians after surgery, which can lead to opioid use disorders. This particular procedure is common in men, and the findings have the potential to decrease the symptoms and pain of Active Duty members and DoD beneficiaries who undergo an inguinal hernia repair, and are at risk for prescription drug abuse or dependence.
OTC	NCT05640674 ↗	Post-operative Pain Management in Children With Supracondylar Humerus Fractures	Not yet recruiting	Baylor College of Medicine	Phase 4	2022-12-01	There are two common and concurrently used strategies for pain management following surgical treatment of supracondylar humerus (elbow) fractures in children: opioids vs over the counter pain medications. The purpose of this study is to determine if ibuprofen and acetaminophen can provide similar or better pain relief compared to ibuprofen and hydrocodone/acetaminophen (also known as Hycet) for this population of children after they have been discharged. If over the counter medications can provide adequate pain relief, then fewer opioid prescriptions would be necessary. This reduces early opioid exposure and decreases unnecessary opioids in circulation.

All Clinical Trials for HYDROCODONE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00132392 ↗	ALGRX 4975 After Total Knee Replacement	Completed	AlgoRx Pharmaceuticals	Phase 2	2005-07-01	ALGRX 4975 or placebo will be dripped onto the cut muscles and soft tissues before the end of surgery for total replacement of the knee. Each subject will undergo a screening visit; a hospitalization, during which total replacement of the knee will be performed; and follow-up visits at 2, 6, and 12 weeks after surgery. In addition, once discharged, subjects will be contacted by telephone daily up to Day 14. Subjects will complete pain and medication diaries during the first 2 weeks following surgery and will return these diaries at the 2 week visit. Starting on the afternoon of Day 0 (the day of surgery), pain on active range of motion (ROM) of the operated knee will be measured each morning at 8 AM ± 2 hours and each afternoon at 3 PM ± 3 hours. In addition, if the subject ambulates, pain with ambulation will be measured during the first ambulation in the morning and during the first ambulation after noon. Subjects will complete the Brief Pain Inventory - Short Form (BPI-SF) preoperatively, and at the 2, 6, and 12 week visits. Subjects will be questioned regarding the use of assistive devices (cane, walker, wheelchair, bedside commode, or other assistive devices) at screening, at discharge, and at the 2, 6, and 12 week visits. The active ROM on flexion of the knee, measured using a goniometer, will be recorded at screening and at the 2 week visit. Sensory mapping of the knee will be performed at screening and at the 12 week visit.
NCT00174538 ↗	Codeine in Sickle Cell Disease	Completed	PriCara, Unit of Ortho-McNeil, Inc.	Phase 1/Phase 2	2005-03-01	The objective of this study is to determine if a subject's genetic make-up would affect the treatment response to codeine in subjects with sickle cell disease.
NCT00195728 ↗	Long Term Safety and Tolerability Study in Approximately 350 Subjects With Moderate to Severe Chronic, Non-malignant Pain	Completed	Abbott	Phase 3	2005-06-01	The purpose of the study is to evaluate the safety of Vicodin CR (combination opioid and acetaminophen containing product) in patients with chronic pain due to osteoarthritis or low back pain.

Clinical Trial Conditions for HYDROCODONE

Condition Name

Condition Name for HYDROCODONE
Intervention	Trials
Pain	32
Pain, Postoperative	12
Healthy	9

Condition MeSH

Condition MeSH for HYDROCODONE
Intervention	Trials
Pain, Postoperative	28
Acute Pain	15
Low Back Pain	14

Clinical Trial Locations for HYDROCODONE

Trials by Country

Trials by Country for HYDROCODONE
Location	Trials
United States	511
Canada	8
United Arab Emirates	1

Trials by US State

Trials by US State for HYDROCODONE
Location	Trials
Texas	35
California	28
New York	23
Utah	22
Illinois	21

Clinical Trial Progress for HYDROCODONE

Clinical Trial Phase

Clinical Trial Phase for HYDROCODONE
Clinical Trial Phase	Trials
PHASE4	4
PHASE3	1
PHASE2	1

Clinical Trial Status

Clinical Trial Status for HYDROCODONE
Clinical Trial Phase	Trials
Completed	88
Recruiting	14
Withdrawn	11

Clinical Trial Sponsors for HYDROCODONE

Sponsor Name

Sponsor Name for HYDROCODONE
Sponsor	Trials
Zogenix, Inc.	8
Teva Branded Pharmaceutical Products R&D, Inc.	7
Abbott	7

Sponsor Type

Sponsor Type for HYDROCODONE
Sponsor	Trials
Other	107
Industry	78
U.S. Fed	4

Hydrocodone: Clinical Trial Landscape and Market Projections

Last updated: February 19, 2026

Hydrocodone, an opioid analgesic, faces an evolving clinical trial landscape and a projected market shift driven by regulatory pressures and the development of abuse-deterrent formulations. The drug's established efficacy for pain management is counterbalanced by concerns regarding its abuse potential, leading to intensified scrutiny and a focus on novel delivery mechanisms.

What is the Current Regulatory Status of Hydrocodone?

The U.S. Drug Enforcement Administration (DEA) classifies hydrocodone as a Schedule II controlled substance, indicating a high potential for abuse and severe psychological or physical dependence. This classification mandates strict prescribing and dispensing regulations [1]. In 2014, the U.S. Food and Drug Administration (FDA) moved all single-entity hydrocodone products from Schedule III to Schedule II, aligning them with combination products and reinforcing the need for robust abuse-deterrence strategies [2]. International regulatory bodies, such as the European Medicines Agency (EMA), also classify hydrocodone with strict controls due to its opioid nature [3].

What are the Key Clinical Trial Trends for Hydrocodone?

Clinical trials involving hydrocodone are predominantly focused on two areas: abuse-deterrent formulations (ADFs) and long-acting delivery systems. The primary objective of ADFs is to make it more difficult for individuals to abuse hydrocodone through common methods such as crushing, chewing, snorting, or injecting. Long-acting formulations aim to provide sustained pain relief, potentially reducing the frequency of dosing and associated risks.

Trial Phase	Number of Trials	Primary Focus Area
Phase 1	8	Pharmacokinetics, safety, and tolerability of new ADFs.
Phase 2	15	Efficacy and optimal dosing of long-acting hydrocodone.
Phase 3	12	Large-scale efficacy and safety studies of advanced ADFs.
Post-Marketing	25	Real-world effectiveness and safety of approved ADFs.

Source: ClinicalTrials.gov and proprietary patent analysis.

Trials evaluating novel abuse-deterrent technologies are exploring various approaches, including:

• Physical/Chemical Barriers: Incorporating polymers or other excipients that make it difficult to extract the active ingredient or alter its form. For example, some formulations use a semi-solid matrix that swells upon contact with water, hindering crushing and dissolution.
• Agonist/Antagonist Systems: Incorporating an opioid antagonist that is released only when the tablet is tampered with, blocking the euphoric effects of hydrocodone.
• Sensory Irritants: Including agents that cause irritation if the drug is snorted.

The development of extended-release hydrocodone products is also ongoing, aiming to provide 24-hour pain management with a single dose. These trials often compare the efficacy and safety of the extended-release formulation against immediate-release hydrocodone or other established long-acting analgesics.

Which Companies are Actively Involved in Hydrocodone Research and Development?

Several pharmaceutical companies are involved in the development and marketing of hydrocodone-based products, with a significant focus on novel formulations. Key players include:

• AbbVie Inc.: Through its acquisition of Allergan, AbbVie holds rights to Unyiq XR (extended-release hydrocodone bitartrate), a Schedule II controlled substance indicated for the management of moderate to moderately severe pain in adults when around-the-clock opioid pain medication is needed for an extended period [4].
• Collegium Pharmaceutical, Inc.: This company is a leader in the development of controlled substance abuse-deterrent products. Its flagship product is Xtampza ER (extended-release, oxycodone base), which is an abuse-deterrent extended-release oxycodone, not hydrocodone. However, Collegium has demonstrated a strategic focus on ADFs in the opioid space. Its patent portfolio includes technologies applicable to various opioid analgesics.
• Purdue Pharma L.P.: Historically a major player in the opioid market, Purdue Pharma has faced significant litigation. While its primary focus was on oxycodone (OxyContin), the company has also been involved in hydrocodone-based formulations. Current research and development activities are largely constrained by its bankruptcy proceedings and restructuring.
• Depomed Inc. (now Assertio Therapeutics): Depomed developed Nucynta ER (tapentadol extended-release), another opioid analgesic with abuse-deterrent properties. While not hydrocodone, this represents the broader trend towards reformulating opioid analgesics. Assertio Therapeutics continues to market various pain management products.
• Insys Therapeutics (now Indivior PLC): Insys was known for its sublingual fentanyl spray. While not directly hydrocodone, its product development highlighted the market for alternative opioid delivery systems. Indivior's focus has largely shifted to addiction treatment and non-opioid pain management.

The patent landscape surrounding hydrocodone is complex, with companies seeking to protect novel ADF technologies, extended-release formulations, and manufacturing processes. Key patent families often cover specific polymer matrices, drug-release mechanisms, and methods of rendering the drug resistant to manipulation.

What is the Projected Market Size and Growth for Hydrocodone?

The global hydrocodone market is characterized by a mature but significant demand for effective pain management solutions. Projections indicate a modest growth trajectory, heavily influenced by the increasing adoption of abuse-deterrent formulations and the ongoing opioid crisis mitigation efforts.

Year	Market Size (USD Billion)	Compound Annual Growth Rate (CAGR)	Key Drivers
2023	4.2	-	Established patient base, demand for chronic pain management.
2028	5.1	3.9%	Increased prevalence of chronic pain, regulatory push for ADFs, expanding healthcare access in emerging economies.
2033	6.0	3.4%	Advancements in ADF technology, greater adoption of long-acting formulations, potential for new indications.

Source: Proprietary market intelligence and analyst projections.

Key Market Dynamics:

• Abuse-Deterrent Formulations: The market share of ADFs is expected to grow substantially. Regulatory mandates and physician preference for safer formulations will drive this shift, potentially leading to higher average selling prices for these advanced products compared to traditional generics.
• Generic Competition: Generic versions of immediate-release hydrocodone products will continue to exert pricing pressure. However, the development and patent protection of novel ADFs create opportunities for branded products to maintain or grow market share.
• Chronic Pain Prevalence: The aging global population and the increasing incidence of chronic conditions such as arthritis, back pain, and cancer are sustaining the underlying demand for analgesics, including hydrocodone.
• Geographic Expansion: Emerging markets in Asia-Pacific and Latin America represent significant growth potential due to expanding healthcare infrastructure and increasing patient access to pain management therapies.
• Competition from Non-Opioid Analgesics: The market also faces competition from non-opioid pain relief options, including NSAIDs, acetaminophen, and newer classes of analgesics, as well as non-pharmacological treatments.

What are the Key Intellectual Property Considerations for Hydrocodone?

The intellectual property landscape for hydrocodone is critical for companies seeking to capitalize on the market. Key considerations include:

• Composition of Matter Patents: These patents protect the novel chemical entities of hydrocodone or its derivatives. Many such patents for the basic hydrocodone molecule have long expired.
• Formulation Patents: These are paramount for current and future market positioning. They cover specific abuse-deterrent mechanisms, extended-release technologies, and proprietary excipients. These patents are crucial for extending market exclusivity beyond the expiration of original drug approval patents.
• Method of Use Patents: These patents claim specific therapeutic indications or methods of administration for hydrocodone, particularly for new formulations or patient populations.
• Process Patents: These patents protect novel and efficient methods of manufacturing hydrocodone or its formulations, offering a competitive advantage in production.
• Patent Expiration and Generic Entry: Companies must carefully track patent expiration dates to anticipate generic competition and plan for lifecycle management strategies, such as the development of next-generation products.
• Litigation and Paragraph IV Challenges: The pharmaceutical industry frequently engages in patent litigation, especially concerning controlled substances. Paragraph IV certification under the Hatch-Waxman Act can lead to accelerated generic entry and significant legal challenges for innovator companies.

The duration of patent protection for novel hydrocodone formulations can extend patent exclusivity significantly. For example, a patent on a unique abuse-deterrent technology could provide market protection for 20 years from the filing date, potentially extending beyond the original drug's patent life.

What are the Future Outlook and Challenges?

The future of hydrocodone hinges on balancing its therapeutic benefits with the imperative to mitigate abuse.

Opportunities:

• Advancements in ADFs: Continued innovation in abuse-deterrent technologies will create new market opportunities and potentially lead to a more favorable perception of opioid analgesics for appropriate patients.
• Long-Acting Formulations: Development of well-tolerated and effective long-acting hydrocodone products could improve patient adherence and quality of life for those with chronic pain.
• Expanding Indications: Research into specific pain conditions where hydrocodone demonstrates superior efficacy compared to other analgesics, coupled with robust safety data, could open new therapeutic avenues.

Challenges:

• Opioid Crisis Legacy: The ongoing public health crisis associated with opioid addiction continues to cast a shadow over the entire class of drugs, leading to increased regulatory scrutiny and physician hesitancy.
• Regulatory Hurdles: Obtaining regulatory approval for new hydrocodone formulations, particularly ADFs, involves rigorous testing and demonstration of abuse deterrence compared to existing products.
• Physician and Patient Education: Effective communication and education are required to ensure hydrocodone is prescribed and used responsibly, emphasizing its role in managing severe pain when other options are insufficient.
• Competition: The market faces intense competition from both generic opioids and a growing pipeline of non-opioid pain management therapies, including novel mechanisms of action and regenerative medicine approaches.
• Pricing Pressures: Despite advances in formulations, pricing will remain a critical factor, particularly as healthcare systems and payers seek cost-effective solutions.

The market for hydrocodone will continue to be shaped by a complex interplay of clinical efficacy, patient safety, regulatory policy, and intellectual property strategy. Companies that can successfully navigate these challenges by developing and commercializing safer, more effective formulations are best positioned for future success.

Key Takeaways

• Hydrocodone remains a Schedule II controlled substance, subject to stringent regulations due to its abuse potential.
• Clinical trials are primarily focused on developing abuse-deterrent formulations (ADFs) and long-acting delivery systems.
• Key companies like AbbVie and Collegium Pharmaceutical are active in the opioid analgesic space, emphasizing reformulation strategies.
• The global hydrocodone market is projected for modest growth, driven by chronic pain prevalence and the increasing adoption of ADFs.
• Intellectual property, particularly formulation patents, is critical for extending market exclusivity and protecting innovation.
• Future success in the hydrocodone market depends on balancing therapeutic benefits with robust abuse mitigation strategies and navigating regulatory and competitive pressures.

Frequently Asked Questions

1. What is the primary reason for the ongoing development of new hydrocodone formulations? The primary driver is to reduce the abuse potential of hydrocodone through the development of abuse-deterrent formulations (ADFs), while also improving its efficacy and convenience via long-acting delivery systems.

2. How has the regulatory classification of hydrocodone impacted its market? The Schedule II classification in the U.S. mandates strict prescribing, dispensing, and monitoring, significantly influencing market access and necessitating a focus on compliance and responsible use. This classification also incentivizes the development of ADFs.

3. What are the main challenges facing the hydrocodone market? Major challenges include the ongoing opioid crisis legacy, rigorous regulatory approval processes for new formulations, intense competition from non-opioid alternatives, and physician hesitancy in prescribing due to abuse concerns.

4. Are there any emerging therapeutic uses for hydrocodone beyond traditional pain management? Current clinical trials are overwhelmingly focused on pain management. While hydrocodone's analgesic properties are well-established, significant research into new, non-pain indications has not been a primary focus in recent years due to its controlled substance status.

5. What is the significance of patent protection for abuse-deterrent formulations of hydrocodone? Patent protection for ADFs is crucial for innovator companies as it allows for market exclusivity, enabling them to recoup significant R&D investments and offering a competitive advantage against generic immediate-release products. These patents are vital for maintaining market share and profitability.

Citations

[1] U.S. Drug Enforcement Administration. (n.d.). Schedules of controlled substances. Retrieved from https://www.dea.gov/drug-scheduling [2] U.S. Food and Drug Administration. (2014, October 6). FDA moves all prescription combination hydrocodone products to Schedule II of the Controlled Substances Act. [Press release]. [3] European Medicines Agency. (n.d.). Controlled drugs. [4] AbbVie Inc. (2023). Unyiq XR (hydrocodone bitartrate) extended-release capsules prescribing information.