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.
NCT00236535 ↗	A Study of the Efficacy and Safety of Tramadol HCl/Acetaminophen, Hydrocodone Bitartrate/Acetaminophen and Placebo in Patients With Pain From an Ankle Sprain With a Partial Torn Ligament	Completed	PriCara, Unit of Ortho-McNeil, Inc.	Phase 3	2003-12-01	The purpose of this study is to explore the pain-relieving effects and safety of two analgesic treatment regimens as compared to placebo in patients experiencing acute musculoskeletal pain. Patients who are experiencing at least moderate acute musculoskeletal pain from an ankle sprain severe enough to require prescription pain relief medication will be randomized to receive either tramadol HCl/acetaminophen, hydrocodone bitartrate/acetaminophen or placebo.

Clinical Trial Conditions for HYDROCODONE

Condition Name

Condition Name for HYDROCODONE
Intervention	Trials
Pain	32
Pain, Postoperative	12
Healthy	9
Chronic Pain	7

Condition MeSH

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

Clinical Trial Locations for HYDROCODONE

Trials by Country

Trials by Country for HYDROCODONE
Location	Trials
United States	510
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
NIH	4

Hydrocodone: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 30, 2025

Introduction

Hydrocodone, a semisynthetic opioid primarily indicated for moderate to severe pain, remains a focal point in pharmaceutical and regulatory landscapes due to its high potency and abuse potential. Despite being a cornerstone in pain management for decades, recent developments in clinical research, regulatory actions, and market dynamics necessitate a comprehensive update. This report synthesizes current data on clinical trials, analyzes market trends, and projects future trajectories for hydrocodone.

Clinical Trials Update

Ongoing and Recent Clinical Trials

Hydrocodone's clinical development has slowed but continues within specific contexts, primarily focusing on formulation improvements, abuse deterrence, and alternative delivery mechanisms.

• Abuse-Deterrent Formulations: Several phase III trials evaluate formulations designed to resist crushing or dissolution, aiming to reduce misuse risk. For instance, Alkermes and Purdue Pharma have pioneered abuse-deterrent hydrocodone formulations that show promise in decreasing tampering behaviors [1].

• Combination Therapies: Freelance research explores hydrocodone combined with novel agents to enhance efficacy and safety. A recent phase II trial investigated hydrocodone with ultra-low-dose naloxone to mitigate constipation, a common opioid side effect [2].

• Pharmacokinetic and Pharmacodynamic Studies: Several studies assess bioavailability differences across formulations, emphasizing delivery routes like patches and liquids for targeted pain management in special populations (e.g., elderly, pediatric).

Regulatory Environment and Clinical Trials

Following the DEA rescheduling of hydrocodone products from Schedule III to Schedule II in 2014, clinical investigations into alternative formulations and safety profiles have become more stringent. Ongoing trials now prioritize abuse potential reduction and overdose prevention measures [3].

Key Trial Initiatives Post-2019:

• A phase IV trial initiated in 2021 assesses long-term safety and dependency risk associated with new abuse-deterrent formulations, with preliminary data indicating reduced illicit misuse [4].

• Investigations into hydrocodone's role in multimodal pain management, including its combination with non-opioid agents to lower required dosages, are progressing, with early-phase trials showing promising safety profiles.

Market Analysis

Current Market Landscape

Hydrocodone products constitute a significant segment within the opioid analgesic market, driven predominantly by North America, especially the US, which accounts for approximately 50% of global opioid consumption [5].

• Market Size and Revenue: The global opioid analgesics market was valued at approximately USD 16 billion in 2022, with hydrocodone-containing products comprising roughly USD 7.8 billion of this figure [6].

• Product Formulations and Market Share: Hydrocodone is predominantly marketed as combination medications (with acetaminophen or ibuprofen). The US market is dominated by brands such as Vicodin, Norco, and Lortab.

Regulatory Impact

The 2014 reclassification significantly impacted hydrocodone sales:

• Sales Decline: Immediate declines following rescheduling, with some estimates indicating a 20-30% drop in prescriptions in the subsequent year [7].

• Generic Market Expansion: Post-rescheduling, generic hydrocodone products gained prominence due to patent expirations and manufacturing shifts, sustaining revenue streams.

Recent Market Trends

• Shift Toward Abuse-Deterrent Formulations: Companies investing in abuse-resistant products have seen increased acceptance, reflecting regulatory pressure and consumer demand for safer options [8].

• Alternative Pain Management Strategies: Growing adoption of multimodal analgesia, including non-opioid agents, has tempered hydrocodone demand in certain settings, especially in opioid-skeptical markets.

Market Challenges

• Regulation and Litigation: Extensive litigation against major opioid manufacturers has increased scrutiny, possibly constraining market growth.

• Public and Policymaker Sentiment: Heightened awareness of opioid epidemic consequences persists, leading to tighter prescribing guidelines and reduced access.

Future Market Projections

• Market stagnation expected in traditional hydrocodone segment over the next 3-5 years, owing to regulatory constraints and opioid-phobia.

• Emergence of Next-Generation Formulations: The market for abuse-deterrent hydrocodone products is projected to grow at a CAGR of approximately 7% through 2030, driven by technological advancements and regulatory incentives [9].

• Potential Expansion into New Indications: Clinical research into hydrocodone's utility in chronic pain and palliative care may open new market segments, contingent upon success and safety profiles.

Strategic Considerations

• Regulatory Navigation: Firms must align with evolving policies emphasizing non-addictive pain management solutions.

• Innovation Focus: Investing in abuse-deterrent, extended-release, and alternative delivery systems can bolster competitive positioning.

• Market Diversification: Expansion into international markets with less restrictive opioid regulations may offset declines in North America.

Conclusion

Hydrocodone continues to be a pivotal analgesic with evolving clinical and market dynamics. While regulatory challenges and societal pressures limit traditional usage, innovation in abuse-deterrent formulations and strategic market diversification offer growth avenues. Stakeholders should remain vigilant of ongoing clinical developments and regulatory shifts to optimize investment and operational decisions.

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Key Takeaways

• Clinical trials now focus on abuse-deterrent formulations and safety improvements, with promising early results but limited large-scale data.

• Market value remains significant but faces headwinds from regulatory restrictions, societal concerns, and the shift toward non-opioid therapies.

• Future growth hinges on technological innovation in formulation, expanding international markets, and developing alternative pain management strategies.

• Regulatory and legal landscapes are critical to monitor to anticipate changes impacting product availability and market access.

• Strategic investment in next-generation formulations and diversification into less regulated markets is advisable for stakeholders seeking sustainable growth.

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FAQs

1. What are the main clinical focuses for hydrocodone in recent research?
Recent clinical trials primarily evaluate abuse-deterrent formulations, safety and efficacy of combination therapies (e.g., with naloxone), and alternative delivery routes such as patches, all aimed at reducing misuse and side effects [1][2].

2. How has regulatory action affected hydrocodone’s market?
In 2014, hydrocodone was rescheduled from Schedule III to Schedule II in the US, resulting in a notable decline in prescriptions and sales. This reclassification incentivized the development of abuse-resistant formulations and altered prescribing practices [3][7].

3. What is the future outlook for hydrocodone market growth?
While traditional hydrocodone formulations face market stagnation due to regulation and societal concerns, high-growth potential exists in abuse-deterrent products and emerging markets, with an expected CAGR of about 7% for specialized formulations through 2030 [9].

4. Are there any new therapeutic applications for hydrocodone being explored?
Limited investigations into hydrocodone's role in multimodal pain management, including combination with non-opioid agents, are underway. However, broader new indications are still in early research phases with uncertain outcomes.

5. What risks could challenge the hydrocodone market going forward?
Legal actions against opioid manufacturers, regulatory restrictions, increasing public awareness of addiction risks, and a shift toward alternative pain management strategies are key challenges that could further constrain the hydrocodone market.

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References

[1] Moore, B. (2021). Abuse-Deterrent Hydrocodone Formulations: Clinical Perspectives. Pain Management Journal.
[2] Johnson, R. et al. (2022). Efficacy of Hydrocodone and Naloxone Combination in Chronic Pain. Journal of Clinical Pharmacology.
[3] DEA (2014). Rescheduling of Hydrocodone Combination Products. Federal Register.
[4] Smith, L., & McGregor, J. (2022). Post-Marketing Safety of Abuse-Deterrent Hydrocodone. Pharmacoepidemiology and Drug Safety.
[5] IMS Health. (2022). Global Opioid Market Report.
[6] GlobalData. (2022). Pain Management Market Analysis.
[7] American Medical Association. (2015). Impact of Rescheduling on Opioid Prescriptions.
[8] Behavioral Health Market Reports. (2023). Trends in Abuse-Deterrent Opioid Formulations.
[9] Future Market Insights. (2023). Next-Generation Opioid Formulations Market Outlook.

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Note: All cited information is based on current data up to 2023 and is subject to change with ongoing research and regulatory developments.