CLINICAL TRIALS PROFILE FOR ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE

505(b)(2) Clinical Trials for ACETAMINOPHEN; OXYCODONE 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	NCT01588158 ↗	Patient Satisfaction With Pain Relief After Ambulatory Hand Surgery	Terminated	Massachusetts General Hospital	Phase 4	2012-07-01	Adequate pain relief has been a priority of the Joint Commission and is featured on national inpatient surveys such as the H-CAHPS. When considering methods for improving satisfaction with pain relief in the United States, a great deal of emphasis has been placed on opioid pain medications. Some of this emphasis on opioid pain medication is driven by the pharmaceutical industry and by advocacy groups with ties to the pharmaceutical industry. There is evidence that the "pain is the fifth vital sign" campaign of the Joint Commission led to an increased incidence of prescription of opioids, but there is less evidence of improved satisfaction with pain relief. There is some evidence of an increase in opioid-related adverse events. As the sales of opioids have tripled from 1999-2008, so has the number of deaths caused by opioid overdose; 14,800 in 2008. The number of visits to the Emergency Department for opioid overdose doubled between 2004 and 2008. Patients in other countries take far less opioid pain medication and are equally satisfied with pain relief. For instance, Lindenhovius et al. found in a retrospective study that Dutch patients take a weak (Tramadol) or no opioid pain medication after ankle fracture surgery and have comparable or better satisfaction with pain relief than American patients, most of whom take oxycodone. That study was repeated prospectively (unpublished) and confirmed that Dutch patients do not feel their pain is undertreated. A study of morphine use after a femur fracture demonstrated that American patients used far more than Vietnamese patients (30 mg/kg versus 0.9 mg/kg), but were more dissatisfied with their pain relief. These sociological differences are striking and suggest strongly that personal factors may be the most important determinant of satisfaction with pain relief. It is our impression that most American hand surgeons give patients a prescription for an opioid pain medication after carpal tunnel release, and that is certainly true in our practice. This seems to be based primarily on the outliers, and intended to avoid confrontation with patients that desire opioids; however, most patients take little or no narcotic pain medication, and many who do use the opioids complain of the side effects-nausea and pruritis in particular. It is therefore not clear whether routine opioids is the optimal pain management strategy after carpal tunnel release. In the study of Stahl et al. from Israel, patients were prescribed acetaminophen rather than opioids after carpal tunnel release and only 20 of 50 patients used acetaminophen; 30 patients did not use acetaminophen or other pain medication at all after the operation. Our aim is to determine if there is a difference in satisfaction with pain relief between patients advised to take opioids compared to patients advised to use over the counter acetaminophen after carpal tunnel release under local anesthesia. A secondary aim is to determine if personal factors account for more of the variability in satisfaction with pain relief than opioid strategy.
OTC	NCT01691690 ↗	Analgesic Effect of IV Acetaminophen in Tonsillectomies	Completed	Nationwide Children's Hospital	Phase 2	2012-10-01	Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate pain for pediatric patients. Its common use (particularly in oral form) is underscored by its wide therapeutic window, safety profile, over the counter accessibility, lack of adverse systemic effects (as compared with NSAIDS and opioids) when given in appropriate doses. Although the exact anti-nociceptive mechanisms of acetaminophen continue to be elucidated, these mechanisms appear to be multi-factorial and include central inhibition of the cyclo-oxygenase (COX) enzyme leading to decreased production of prostaglandins from arachidonic acid, interference with serotonergic descending pain pathways, indirect activation of cannabinoid 1 (CB1) receptors and inhibition of nitric oxide pathways through N-methyl-D-aspartate (NMDA) or substance P. Of the above mechanisms, the most commonly known is that of central inhibition of COX enzymes by which the decreased production of prostaglandins diminish the release of excitatory transmitters of substance P and glutamate which are both involved in nociceptive transmission (Anderson, 2008; Smith, 2011). To date, several studies have shown acetaminophen's opioid sparing effect in the pediatric population when given by the rectal or intravenous routes (Korpela et al, 1999; Dashti et al, 2009; Hong et al, 2010).
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 ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00092313 ↗	A Study of Two Approved Drugs in the Treatment of Postoperative Dental Pain (0966-182)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2002-06-01	The purpose of this study is to compare the safety and effectiveness of two approved drugs in the treatment of pain following dental surgery.
NCT00092326 ↗	A Study of Two Approved Drugs in the Treatment of Postoperative Dental Pain (0966-183)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2002-06-01	The purpose of this study is to compare the safety and effectiveness of two approved drugs in the treatment of pain following dental surgery.
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.
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.
NCT00290589 ↗	A Trial of Corticosteroids for Low Back Pain	Completed	Montefiore Medical Center	Phase 3	2003-06-01	Low back pain is a common symptom that functionally disables many people. When the low back pain is accompanied by pain that shoots down the leg, it is felt to be caused by a herniated disc. We are conducting this study to determine if a powerful anti-inflammatory agent will decrease the pain and functional impairment that is associated with this illness.
NCT00312221 ↗	Safety and Efficacy of Buprenorphine Transdermal System (BTDS) in Subjects With Moderate to Severe Osteoarthritis Pain	Terminated	Purdue Pharma LP	Phase 3	2004-04-01	The objective of this study is to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (20 mg) in comparison to the buprenorphine transdermal system (5 mg) and oxycodone immediate release in subjects with moderate to severe osteoarthritis pain currently treated with oral opioids. The double-blind treatment intervention duration is 12 weeks during which time supplemental analgesic medication (acetaminophen, ibuprofen, immediate release oxycodone) will be provided to all subjects in addition to study drug.

Clinical Trial Conditions for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE

Condition Name

Condition Name for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Intervention	Trials
Pain, Postoperative	23
Pain	17
Postoperative Pain	13
Opioid Use	8

Condition MeSH

Condition MeSH for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Intervention	Trials
Pain, Postoperative	56
Acute Pain	12
Osteoarthritis	9
Fractures, Bone	9

Clinical Trial Locations for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE

Trials by Country

Trials by Country for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Location	Trials
United States	271
Canada	13
Norway	1
Lebanon	1
Korea, Republic of	1

Trials by US State

Trials by US State for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Location	Trials
New York	31
California	24
Pennsylvania	18
Texas	12
North Carolina	11

Clinical Trial Progress for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Clinical Trial Phase	Trials
Phase 4	65
Phase 3	29
Phase 2	17

Clinical Trial Status

Clinical Trial Status for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	59
Recruiting	25
Terminated	19

Clinical Trial Sponsors for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE

Sponsor Name

Sponsor Name for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Sponsor	Trials
Montefiore Medical Center	8
Purdue Pharma LP	7
University of California, Los Angeles	7

Sponsor Type

Sponsor Type for ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Sponsor	Trials
Other	154
Industry	37
U.S. Fed	3