CLINICAL TRIALS PROFILE FOR HYDROMORPHONE HYDROCHLORIDE

505(b)(2) Clinical Trials for HYDROMORPHONE 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
OTC	NCT00245375 ↗	A Trial Comparing Combination Therapy of Acetaminophen Plus Ibuprofen Versus Tylenol #3 for the Treatment of Pain After Outpatient Surgery	Completed	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.	N/A	2005-01-01	Increasingly in general surgery, the investigators are conducting outpatient day surgery. Ambulatory surgery currently comprises 60 to 70% of surgeries performed in North America. These patients all require some form of analgesia which can be taken at home in the first few days after the surgery. The current standard at the investigators' centre and many others in the maritime provinces is to provide a prescription for oral acetaminophen plus codeine or oxycodone (Tylenol #3®, Percocet ®). Some patients may receive more potent opioids such as oral hydromorphone (Dilaudid®). Unfortunately, the most commonly prescribed medication (Tylenol #3®) is often poorly tolerated by patients, has several undesirable side effects, and may not provide effective pain relief. In the investigators' experience, non-steroidal anti-inflammatory drugs (NSAIDs) are uncommonly a routine addition to the home analgesic regimen. Tylenol #3®, in the investigators' experience and opinion, is a poor post surgical pain medication. They hope to show that a combination of ibuprofen and acetaminophen is better for pain relief after these procedures. The combination of acetaminophen and ibuprofen would be a safe, cheap, and readily available regimen. Unfortunately, as the prescribing practices of surgeons are old habits, it will require a very convincing argument to get them to change their practices. A randomized controlled trial comparing these two regimens, the investigators hope, would be a powerful enough argument. The hypothesis of this study, therefore, is that the pain control provided by a combination of acetaminophen plus ibuprofen (650 mg/400 mg four times per day) will be superior to Tylenol #3® (600 mg acetaminophen/60 mg codeine/15 mg caffeine four times per day). This study will attempt to enroll 150 patients in total. Eligible patients will be identified by their attending surgeon and contacted by study personnel. Patients who enroll in the study will undergo their surgery in the usual manner. After the surgery, in the recovery room, once they are ready to go home, they will be randomized to receive combination A or B and be given a week's worth of pain medication. They will then go home and take this medication as directed. They will record their pain intensity and pain relief once per day using a diary provided in the study package. One week after their surgery, they will return to the hospital clinic and be seen by the study nurse. They will hand over the diary and any unused medication. They will also be asked several questions regarding their overall satisfaction, incidence of side effects, and how long until they were pain free. The risks of participating in this study are minimal from the risks inherent to the procedures and medications the patients would receive within the standard of care. Ibuprofen is a commonly used NSAID which is widely available over the counter and has an established safety profile. The most common adverse effects of ibuprofen and other NSAIDs are gastrointestinal bleeding and ulceration. Other less common adverse effects include nephrotoxicity, hypersensitivity reactions, hepatic dysfunction (longterm use), and cognitive dysfunction. The investigators' patients will be selected to exclude those most at risk for these complications (see exclusion criteria). Acetaminophen has few side effects, with no adverse effects on platelet function and no evidence of gastric irritation.
OTC	NCT00245375 ↗	A Trial Comparing Combination Therapy of Acetaminophen Plus Ibuprofen Versus Tylenol #3 for the Treatment of Pain After Outpatient Surgery	Completed	Nova Scotia Health Authority	N/A	2005-01-01	Increasingly in general surgery, the investigators are conducting outpatient day surgery. Ambulatory surgery currently comprises 60 to 70% of surgeries performed in North America. These patients all require some form of analgesia which can be taken at home in the first few days after the surgery. The current standard at the investigators' centre and many others in the maritime provinces is to provide a prescription for oral acetaminophen plus codeine or oxycodone (Tylenol #3®, Percocet ®). Some patients may receive more potent opioids such as oral hydromorphone (Dilaudid®). Unfortunately, the most commonly prescribed medication (Tylenol #3®) is often poorly tolerated by patients, has several undesirable side effects, and may not provide effective pain relief. In the investigators' experience, non-steroidal anti-inflammatory drugs (NSAIDs) are uncommonly a routine addition to the home analgesic regimen. Tylenol #3®, in the investigators' experience and opinion, is a poor post surgical pain medication. They hope to show that a combination of ibuprofen and acetaminophen is better for pain relief after these procedures. The combination of acetaminophen and ibuprofen would be a safe, cheap, and readily available regimen. Unfortunately, as the prescribing practices of surgeons are old habits, it will require a very convincing argument to get them to change their practices. A randomized controlled trial comparing these two regimens, the investigators hope, would be a powerful enough argument. The hypothesis of this study, therefore, is that the pain control provided by a combination of acetaminophen plus ibuprofen (650 mg/400 mg four times per day) will be superior to Tylenol #3® (600 mg acetaminophen/60 mg codeine/15 mg caffeine four times per day). This study will attempt to enroll 150 patients in total. Eligible patients will be identified by their attending surgeon and contacted by study personnel. Patients who enroll in the study will undergo their surgery in the usual manner. After the surgery, in the recovery room, once they are ready to go home, they will be randomized to receive combination A or B and be given a week's worth of pain medication. They will then go home and take this medication as directed. They will record their pain intensity and pain relief once per day using a diary provided in the study package. One week after their surgery, they will return to the hospital clinic and be seen by the study nurse. They will hand over the diary and any unused medication. They will also be asked several questions regarding their overall satisfaction, incidence of side effects, and how long until they were pain free. The risks of participating in this study are minimal from the risks inherent to the procedures and medications the patients would receive within the standard of care. Ibuprofen is a commonly used NSAID which is widely available over the counter and has an established safety profile. The most common adverse effects of ibuprofen and other NSAIDs are gastrointestinal bleeding and ulceration. Other less common adverse effects include nephrotoxicity, hypersensitivity reactions, hepatic dysfunction (longterm use), and cognitive dysfunction. The investigators' patients will be selected to exclude those most at risk for these complications (see exclusion criteria). Acetaminophen has few side effects, with no adverse effects on platelet function and no evidence of gastric irritation.
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.

All Clinical Trials for HYDROMORPHONE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00003115 ↗	Epidural Hydromorphone Compared With Hydromorphone Infusion in Treating Patients With Prostate Cancer Undergoing Radical Prostatectomy	Completed	Roswell Park Cancer Institute	Phase 3	1996-06-01	RATIONALE: Giving hydromorphone in different ways may relieve the pain associated with cancer surgery. PURPOSE: Randomized double-blinded phase III trial to compare the effectiveness of epidural hydromorphone with hydromorphone infusion in patients with prostate cancer undergoing radical prostatectomy.
NCT00125801 ↗	The Pain Pen for Breakthrough Cancer Pain	Terminated	Erasmus Medical Center	Phase 3	2005-08-01	The purpose of this study is to see whether injection of hydromorphone through a subcutaneous injection device is more effective in treating breakthrough cancer pain than oral morphine.
NCT00134875 ↗	Assessing Abuse Potential of Parenteral Buprenorphine/Naloxone in Non-Dependent Opioid Abusers	Terminated	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	2000-12-01	Buprenorphine, a treatment for opioid dependence, can be mixed with another drug, naloxone, to limit abuse potential. Parenteral administration (intravenous or intramuscular injection) of buprenorphine/naloxone causes withdrawal symptoms in opioid dependent individuals. However, naloxone does not cause withdrawal symptoms in non-dependent opioid abusers. This study will investigate whether naloxone decreases the opioid agonist effect from injected buprenorphine, hence decreasing the abuse potential of buprenorphine/naloxone, in non-dependent opioid abusers.
NCT00134888 ↗	Blockade Efficacy of Buprenorphine/Naloxone For Opioid Dependence	Completed	National Institute on Drug Abuse (NIDA)	N/A	2000-12-01	Buprenorphine, a treatment for opioid dependence, can be mixed with naloxone, to limit abuse potential. The purpose of this study is to examine the effectiveness of buprenorphine/naloxone that is given at less than daily intervals, in order to prevent withdrawal symptoms associated with stopping opioid abuse.
NCT00134914 ↗	Effects of Buprenorphine/Naloxone Administered in Different Ways For Treating Opioid Dependence	Completed	National Institute on Drug Abuse (NIDA)	N/A	1996-08-01	Buprenorphine is a treatment for opioid dependence. Naloxone is given in addition to buprenorphine in order to limit the abuse potential that is commonly associated with buprenorphine. The purpose of this study is to examine the effects of buprenorphine/naloxone when given through different routes and at different doses.

Clinical Trial Conditions for HYDROMORPHONE HYDROCHLORIDE

Condition Name

Condition Name for HYDROMORPHONE HYDROCHLORIDE
Intervention	Trials
Pain	64
Pain, Postoperative	30
Postoperative Pain	26
Acute Pain	19

Condition MeSH

Condition MeSH for HYDROMORPHONE HYDROCHLORIDE
Intervention	Trials
Pain, Postoperative	74
Acute Pain	29
Opioid-Related Disorders	28
Cancer Pain	15

Clinical Trial Locations for HYDROMORPHONE HYDROCHLORIDE

Trials by Country

Trials by Country for HYDROMORPHONE HYDROCHLORIDE
Location	Trials
United States	256
Canada	50
China	24
Germany	6
Austria	4

Trials by US State

Trials by US State for HYDROMORPHONE HYDROCHLORIDE
Location	Trials
New York	40
Texas	19
California	19
Illinois	19
North Carolina	16

Clinical Trial Progress for HYDROMORPHONE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for HYDROMORPHONE HYDROCHLORIDE
Clinical Trial Phase	Trials
PHASE4	12
PHASE3	4
PHASE2	7

Clinical Trial Status

Clinical Trial Status for HYDROMORPHONE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	172
Recruiting	53
Terminated	34

Clinical Trial Sponsors for HYDROMORPHONE HYDROCHLORIDE

Sponsor Name

Sponsor Name for HYDROMORPHONE HYDROCHLORIDE
Sponsor	Trials
Montefiore Medical Center	17
National Institute on Drug Abuse (NIDA)	15
Alza Corporation, DE, USA	14

Sponsor Type

Sponsor Type for HYDROMORPHONE HYDROCHLORIDE
Sponsor	Trials
Other	328
Industry	82
NIH	26

HYDROMORPHONE HYDROCHLORIDE Market Analysis and Financial Projection

Last updated: April 28, 2026

Hydromorphone Hydrochloride: Clinical Trials Update, Market Analysis, and Projection

What is Hydromorphone Hydrochloride’s current clinical status in trials?

Hydromorphone hydrochloride is an established opioid analgesic with an extensive legacy of clinical development tied to oral, extended-release, and abuse-deterrent reformulations. Public trial activity in the US and major regions largely clusters around (1) formulation strategy, (2) opioid stewardship endpoints such as abuse-related outcomes, and (3) perioperative or pain-condition comparisons under modern risk management frameworks.

Trial update (by development theme, not molecule-level novelty):

• Abuse-deterrent and tamper-resistant formulations: trials and post-approval studies focus on expected decreases in “liking” and extraction/liquefaction behaviors, and on pharmacokinetic comparability under manipulated administration conditions.
• Pharmacokinetic and food-effect studies: frequent, smaller studies that quantify exposure differences by formulation and administration status.
• Analgesic efficacy and safety refreshers: pain trials that re-check effect size and safety with updated monitoring and risk controls.

Clinical takeaway: current clinical activity is formulation- and risk-management led rather than “new MOA” led, which shapes both development timelines and the probability distribution of follow-on claims.

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What is driving the market for Hydromorphone Hydrochloride?

Hydromorphone hydrochloride sits in the oral and injectable opioid analgesic market. Demand is driven by a mix of guideline-based use in moderate-to-severe pain and the inpatient and outpatient shift toward standardized pain protocols.

Key market demand drivers

• Chronic and acute pain management pipelines: hospital formularies and ambulatory pathways that standardize stepwise opioid use.
• Conversion and rotation among opioids: hydromorphone is commonly used when patients require potency changes after inadequate response or intolerance to other opioids.
• Formulation evolution: extended-release products and abuse-deterrent lines target payer and formulary preferences under opioid-risk governance.

Key constraints

• Policy and payer utilization controls: prior authorization, dose limits, and tighter dispensing rules.
• Safety and regulatory scrutiny: opioid class restrictions affect uptake and pricing leverage, especially for new formulations.
• Generic competition: most active components have extensive generic availability, which compresses pricing power for mature segments.

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How big is the hydromorphone hydrochloride opportunity and what segments matter most?

The market is best understood by format because pricing and access differ sharply between immediate-release, extended-release, and injectable products, and because abuse-deterrent positioning changes payer behavior.

Segment lens used for projection

1. Immediate-release oral: typically higher volume, lower ASP, strongest generic pressure.
2. Extended-release oral: higher ASP, steeper payer scrutiny, greater value if abuse-deterrent claims are accepted.
3. Injectable (where applicable by geography/form factor): meaningful in inpatient care, pricing tied to hospital contracts.

Competitive landscape (high level)

• Generic hydromorphone products dominate availability and volume, especially where payers favor lowest acquisition cost.
• Brand and reformulated products compete on differentiation around controlled-release and abuse deterrence rather than on core analgesic effect.

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What is the near-term market outlook and pricing trajectory?

Hydromorphone’s near-term trajectory is shaped by:

• Ongoing opioid stewardship programs that curb initiation and emphasize appropriate dose and duration.
• Substitution across opioids when payers tighten access.
• Mature competition that keeps hydromorphone’s unit economics sensitive to mix shifts toward controlled-release where justified.

Expected directionality

• Volume: relatively stable to modestly down in sensitive channels due to stricter opioid prescribing rules, with localized growth where hospitals expand standardized pain protocols.
• Price/ASP: pressured by generics; extended-release differentiation can partially offset, but adoption depends on formulary fit and real-world restrictions.
• Revenue mix: improved share in abuse-deterrent and extended-release categories is the main lever for revenue resilience.

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What is the mid- to long-term projection (base case) for hydromorphone hydrochloride?

Without granular SKU-level unit and ASP data, projection should be framed as directional with mix effects: hydromorphone as a molecule stays embedded in pain management, but growth depends on whether reformulated products gain share within constrained opioid use.

Projection framework used

• Scenario 1 (Base): modest growth in controlled-release mix offsets flat-to-declining IR demand. Net revenue trends sideways to low single-digit growth over multi-year horizon.
• Scenario 2 (Downside): tighter payer rules and substitution to alternative opioids continue; IR and injectable segments decline with limited offset from ER mix. Net revenue declines.
• Scenario 3 (Upside): abuse-deterrent acceptance and payer guideline alignment increase ER/AD penetration; better adherence to risk mitigation expands patient access within controlled bounds. Net revenue grows low-to-mid single digits.

Base case directional call

• Revenue: low single-digit CAGR is plausible only if ER and/or abuse-deterrent share rises faster than IR declines.
• Volume: growth depends on policy environment; otherwise it stays flat with churn.
• Margin: constrained by generic competition; margins improve only with protected differentiation.

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Where are the highest-probability commercial opportunities in the next 3 to 7 years?

1. Abuse-deterrent and tamper-resistant variants with clear payer-ready evidence
   • Target: reduce diversion concerns and align with formulary decision criteria.
2. Extended-release optimization
   • Target: improved tolerability and stable exposure profiles, supporting continuation under stewardship.
3. Hospital pathway integration
   • Target: consistent conversion protocols and standardized discharge plans that keep hydromorphone in the formulary.

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What does the risk-control environment imply for development and market access?

Hydromorphone’s commercialization is tied to opioid-risk infrastructure. Products that support prescriber confidence and compliance workflows (dose guidance, risk messaging, and practical monitoring approaches) tend to have smoother adoption than products that require new care pathways.

Impacts

• Higher evidence burden for differentiation
• Slower uptake for new entrants unless differentiation is meaningful to payers
• Greater dependence on channel strategy (hospital systems versus retail pharmacies)

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Key Takeaways

• Hydromorphone hydrochloride market dynamics are driven by formulation mix (IR versus ER) and abuse-deterrent acceptance rather than by new mechanism-of-action innovation.
• Near-term revenue is likely flat to low growth with price pressure from generics offset only partially by controlled-release or abuse-deterrent share gains.
• Mid-term outcomes hinge on payer and regulatory constraints on opioid prescribing and the speed at which reformulated products become formulary standard of care.

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FAQs

1) Is hydromorphone hydrochloride still seeing clinical trial activity?

Yes, but current activity largely centers on formulation-related endpoints, pharmacokinetics, and abuse-risk-relevant outcomes rather than new MOA development.

2) What patient segments create the most demand for hydromorphone?

Moderate-to-severe pain patients in inpatient settings and chronic pain populations where opioid rotation and standardized pain protocols maintain hydromorphone as a treatment option.

3) How does generic competition affect hydromorphone pricing?

It compresses ASP and limits margin expansion, making differentiation in extended-release or abuse-deterrent categories the main route to revenue resilience.

4) What determines whether abuse-deterrent hydromorphone gains formulary share?

Payer-aligned evidence on abuse-related outcomes, ease of prescribing within opioid stewardship workflows, and demonstration of predictable exposure and tolerability in real-world use.

5) What is the most important variable for market projection?

The mix shift toward higher-value formulations (extended-release and abuse-deterrent) versus continued pressure from opioid policy and generic pricing on immediate-release and other lower-differentiated formats.

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References

[1] US Food and Drug Administration. Drug Trials Snapshots: Hydromorphone (various products). FDA website.
[2] National Library of Medicine. ClinicalTrials.gov. Search results for hydromorphone hydrochloride.
[3] Centers for Disease Control and Prevention. CDC Guideline for Prescribing Opioids for Pain (updated opioid stewardship policy context). CDC website.
[4] FDA. Abuse-Deterrent Opioids Guidance and related regulatory materials. FDA website.