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.
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	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	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.
NCT00298974 ↗	A Study of Pain Relief in Osteoarthritis	Completed	Abbott	Phase 3	2006-02-01	The purpose of this study is to compare the safety and pain-relieving ability of Vicodin CR to placebo in subjects with osteoarthritis (OA) of the hip or knee.

Clinical Trial Conditions for Hydrocodone

Condition Name

Condition Name for Hydrocodone
Intervention	Trials
Pain	32
Pain, Postoperative	12
Healthy	9
Chronic Low Back 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	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
Florida	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 trials update, FDA status, market analysis, and generic/biosimilar exclusivity outlook

Last updated: May 22, 2026

Hydrocodone is a long-established, widely genericized opioid analgesic. Clinical-trial activity is largely incremental (formulations and abuse-deterrent strategies) rather than new active-drug discovery. From a market and exclusivity perspective, hydrocodone’s commercial exposure is dominated by generic competition and product-specific patent estates tied to dosage forms (ER/IR combinations), labeling/indications, and abuse-deterrent technologies.

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What clinical trials are ongoing for hydrocodone and what do recent updates show?

Which trial types are most active in hydrocodone research

Hydrocodone’s contemporary clinical footprint is concentrated in:

• Abuse-deterrent reformulations (ADF), including physical/chemical barriers to extraction or tampering, and studies measuring impact on dose manipulation.
• PK/BE and bridging studies for generic or reformulated products (IR and ER), including co-administration and fed/fasted assessments.
• Label expansion trials are less common than formulation and safety-related work.

What endpoints typically appear in current hydrocodone studies

Common primary/secondary endpoints:

• Relative bioavailability via AUC and Cmax comparability for generic/alternate formulations.
• Opioid misuse proxy endpoints for abuse-deterrent claims, such as drug-release profile or manipulation-related outcomes.
• Safety endpoints centered on respiratory depression signals, withdrawal risk with taper scenarios, constipation, and adverse-event burden.

How to interpret “updates” for hydrocodone trials

Because hydrocodone’s active ingredient is not new, trial updates are typically:

• Product-level (new strength, ER change, ADF claim refinement, manufacturing site changes)
• Regulatory-pathway-level (bridging to support ANDA or supplemental approvals)
• Compliance- and risk-management-level (Risk Evaluation and Mitigation Strategy elements where applicable to specific branded products)

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How big is the hydrocodone market and what is the revenue outlook through 2030?

Market drivers

Key commercial drivers for hydrocodone are:

• Persistent demand for opioid analgesia in segments that still use hydrocodone-containing products.
• High penetration of generics for most dosage forms and strengths.
• Ongoing shift toward ER formulations and abuse-deterrent labeling strategies in some branded niches (tempered by generic substitution).
• Payer policies and opioid stewardship programs that constrain new utilization growth.

Market headwinds

Commercial risk is concentrated in:

• Regulatory scrutiny of opioid prescribing and opioid risk communications.
• State-level prescribing limits and payer utilization management.
• Litigation and settlement impacts that can affect specific branded products and lead to market exits or restricted promotion.

Projection framing

Hydrocodone market trajectory is expected to be:

• Low-to-moderate growth in nominal terms if underlying pain-management volume holds, but
• Primarily volume-stable due to substitution dynamics (branded to generic) and price compression.

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What patents protect hydrocodone products, and how much of the estate is product-specific?

Hydrocodone’s patent protection is not typically centered on the molecule. Instead, it sits in:

• Formulations (IR vs ER, matrix types, granulation, coatings, drug release control)
• Abuse-deterrent technology claims (where the reference product is branded)
• Method-of-use and dosing-regimen claims tied to specific labeling positions (less common than formulation patents for hydrocodone)

Which jurisdictions matter for enforcement

For US exclusivity and generic-entry timing, the most relevant legal instruments are:

• US patents listed for reference products in FDA’s Orange Book
• US patent term adjustments/extensions (PTA/PTE) that shift expiration dates
• Patent licensing and settlement agreements that control Paragraph IV litigation outcomes

How to assess “how much IP matters” for hydrocodone

For investors and BD teams, the practical IP question is:

• Do any extant US patents cover the specific dosage form strength and release mechanism being targeted by an ANDA?

If not, generic entry risk is high and market prospects are driven by pricing, distribution, and payer coverage rather than exclusivity.

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When does hydrocodone lose exclusivity and what generic entry risks exist?

What “loss of exclusivity” means for hydrocodone

For older opioid actives, exclusivity generally breaks down into:

• Patent expiration (including any granted PTA/PTE)
• Exclusivity periods for branded approvals (where they apply)
• Then the main remaining barrier becomes whether any formulation or method-of-use patents are still in force for the specific dosage form.

Paragraph IV challenge dynamics

Generic entrants commonly use Paragraph IV certifications when:

• A listed patent is expired or not infringed
• The patent is invalid
• Or the product carve-out is achievable via formulation changes that avoid infringement

For hydrocodone, because many competitors are already present, Paragraph IV litigation risk is more likely to be tied to:

• Remaining branded ER/combination products with narrower patent coverage
• Abuse-deterrent claim coverage and whether generic ADF approaches avoid infringement

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What is the Orange Book status of hydrocodone products (IR vs ER, single-entity vs combination)?

Orange Book structure for hydrocodone

The Orange Book typically lists:

• NDA reference products containing hydrocodone (often combinations with acetaminophen)
• Strengths and dosage forms
• Associated US patents with expiration dates
• Exclusivity codes and terms where applicable

Featured-snippet answer

Hydrocodone’s Orange Book landscape is dominated by:

• Many competing ANDA products
• Patent estates that are product-specific, not molecule-wide
• Ongoing listings for ER and abuse-deterrent formulations where available

(Orange Book status is the operative dataset for entry-timing decisions, but accurate, product-by-product status requires the exact NDA/RLD and patent list.)

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Which companies sell hydrocodone and how does the competitive landscape differ by formulation?

Competitive segmentation

Hydrocodone competition splits into:

• Immediate-release (IR) hydrocodone and hydrocodone/acetaminophen generics
• Extended-release (ER) hydrocodone products (smaller segment, more patent/formulation-driven)
• Abuse-deterrent (ADF) niches (more restrictive, but subject to generics that can design around)

What the incumbent strategy typically looks like

For branded niches:

• Maintain ER/ADF differentiation in the face of generic pressure
• Use lifecycle management via reformulation and updated abuse-deterrent evidence
• Leverage payer contracting and REMS-aligned communications where required by product history

What generics can usually do

When no current patents block the specific dosage form:

• ANDA launches can occur quickly after the legal barrier clears
• Differentiation relies on price, distribution, and labeling compliance rather than drug innovation

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How strong is the patent estate for hydrocodone formulations (abuse-deterrent, ER matrices, combination products)?

Typical IP strength profile

In hydrocodone:

• Molecule-level IP is effectively out of play.
• Formulation patents can be the last meaningful IP layer, but they often:
  • Have narrower claim scope than the market expects
  • Are vulnerable to design-around via altered excipients, release profiles, or manufacturing methods

Key technical levers in formulation patents

Patent claim scope often centers on:

• Drug-release kinetics (immediate release vs controlled release)
• Physical barriers to tampering (ADF)
• Co-crystal or chemical modification approaches (less common than matrix/coating)
• Combination stabilization and tolerance profiles for multi-ingredient products

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What hydrocodone clinical evidence matters most for regulatory approval and labeling (PK/BE, abuse deterrence, safety)?

Regulatory evidence typical for US approvals

For most hydrocodone products, the regulatory evidentiary backbone is:

• Bioequivalence (PK/BE) studies for ANDAs
• Safety data aligned to opioid class risks
• Abuse-deterrent assessments for products making ADF claims

Labeling pressure points

Common label-related issues include:

• Dose selection and titration language
• Contraindications and precautions
• Opioid risk communications and guidance on respiratory depression risk

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What patent litigation affects hydrocodone and how do settlements shift generic launch timing?

Litigation pattern for legacy opioids

For older drugs, litigation usually:

• Targets remaining patents on ER/ADF dosage forms
• Drives court timelines and settlement windows that effectively delay or permit launches

How settlements change the commercial calendar

Settlement agreements often:

• Include agreed launch dates
• Define permissible product labeling or formulation design constraints
• Resolve infringement positions while preserving the right to litigate future products

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How does hydrocodone compare with oxycodone, morphine, and tramadol in market and IP risk?

Competitive comparison framework

Hydrocodone generally differs from other opioids in:

• Higher generic penetration across IR products
• A larger share of market constrained by opioid stewardship and payer policy
• IP risk that is dosage-form-specific rather than molecule-specific

Business implication

Compared with newer opioid formulations with more recent lifecycle patents:

• Hydrocodone is more likely to face “immediate generic pressure” once any branded product’s core formulation patents lapse.

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What generic launch scenarios exist for hydrocodone (IR vs ER vs ADF) and what barriers remain?

Scenario map

• Scenario A: Patent-free corridor
  No extant listed patents for the target strength/dosage form. Launch risk is mainly supply and contracting.
• Scenario B: Design-around feasible
  Patents remain but can be avoided by formulation or manufacturing changes. Launch timing depends on certification strategy and litigation risk appetite.
• Scenario C: Litigation creates a hold
  Paragraph IV triggers a stay or settlement delay. Launch date is controlled by agreement or court timeline.

What barriers persist even when patents lapse

Even after patent expiration:

• CMC/validation and manufacturing readiness can bottleneck launch
• Label updates must align to current class safety language
• Payer contracting determines real-world uptake

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Key Takeaways

• Hydrocodone’s R&D activity is mainly formulation and regulatory-bridging rather than new clinical efficacy discovery.
• Market outlook is constrained by opioid stewardship and characterized by generic price pressure and segment-level shifts (IR vs ER, ADF niches).
• Patent protection is product-specific (formulation, ER/ADF, combination features), so generic-entry timing is determined by Orange Book listings for specific NDA strengths and dosage forms.
• Competitive advantage post-barrier is typically operational and commercial (supply, contracting, labeling) more than IP innovation.

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FAQs

1. Do hydrocodone extended-release products have different patent expiration profiles than immediate-release?
2. What abuse-deterrent evidence is usually required to support hydrocodone ADF labeling claims?
3. How do Paragraph IV certifications typically map to hydrocodone formulation patents and design-around strategies?
4. Are hydrocodone clinical trials more likely to be PK/BE studies than outcome trials?
5. Which factors most influence real-world uptake of generic hydrocodone after approval?

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References

1. FDA. Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). U.S. Food and Drug Administration.
2. ClinicalTrials.gov. Hydrocodone trials and study records. National Library of Medicine.