Investigator Initiated Research
Currently, our primary area of research interest is opioid overdose reversal. The FDA approval of nalmefene injectable products* provides additional treatment options for the management of known or suspected opioid overdose.
However, there is limited data on the use of nalmefene HCl Injections in today’s opioid overdose environment. Outcomes associated with the use of nalmefene HCl Injections are of particular interest.
Knoa Pharma LLC typically funds investigator-initiated research (IIR) projects based on a competitive request for proposal (RFP) process. The current cycle has completed. Please check back at a later date for new funding opportunities.
Please note, however, that we will consider research proposals received outside the RFP cycle. Such proposals will also be evaluated by a medical and scientific review committee and will be subject to availability of research funds. If you have questions or would like to submit a research proposal, please contact iirprogram@pharma.com.
*Nalmefene HCl Injection is available in vial and auto-injector forms. Nalmefene HCl vial is a sterile solution containing 2 mg/2 mL (1 mg/mL) for intravenous, intramuscular, and subcutaneous injection, and FDA approved in February 2022. Zurnai™ (nalmefene injection) Auto-injector is a sterile, single-dose auto-injector for intramuscular and subcutaneous injection that delivers 1.5 mg/0.5 mL of nalmefene, and FDA approved in August 2024. See Indications and Important Safety Information for nalmefene HCl injection and Zurnai below.
Collaborative Research Initiatives
The Knoa Pharma LLC Medical Affairs department is pursuing collaborative research to better understand opioid overdose reversal and to inform future research to advance patient care.
For more information or if interested in collaborating on any of the research topics described below, please contact Knoa Pharma at 1-888-726-7535, option 1 or via email at KnoaMedInfo@pharma.com.
Recently Completed Research
Clinical Outcomes from Injectable Nalmefene in the Emergency Department
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Study Location |
UC San Diego Health and El Centro Regional Medical Center (California) |
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Objectives |
To assess the utilization of nalmefene HCl injection for the treatment of known or suspected acute opioid toxicity in the ED setting; and the dosage(s) associated with those reversals |
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Methods |
Retrospective observational study of electronic health records (EHR) |
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Key Outcome Variables |
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Attitudes Toward use of Auto-Injectors During a Medical Emergency
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Objectives |
To measure attitudes among non-medical personnel regarding the use of auto-injectors and nasal sprays during a medical emergency involving an opioid overdose. |
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Methods |
Surveys of general U.S. population, including people with an increased likelihood of providing emergency resuscitation during an opioid overdose. |
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Key Outcome Variables |
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2025 ASHP Midyear Clinical Meeting Poster Abstracts. American Journal of Health-System Pharmacy. In press. doi: 10.1093/ajhp/zxaf258
Research Studies Currently In-Progress
Use of Naloxone Infusion to Treat Opioid Overdose in Hospital Settings
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Objectives |
To systematically document the clinical characteristics and resource utilization associated with the use of naloxone infusion to manage opioid overdoses in ED/hospital settings. |
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Methods |
Retrospective evaluation of electronic health records (EHR). |
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Key Outcome Variables |
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Current Research Interests
Patient Outcomes Following Administration of nalmefene HCI Injection for Treatment of Opioid Overdose
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Objectives |
To assess the reversal of respiratory depression following the administration of nalmefene HCl injection in hospital or EMS settings. |
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Methods |
Observational cohort study of patients who are administered nalmefene HCl injections as part of treatment for a known or suspected opioid overdose. |
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Key Outcome Variables |
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Basic Research Requirements |
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Evaluate Patient Acceptance of Addiction Services following Opioid Overdose Reversal Treatment
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Objectives |
To compare the likelihood of accepting addiction services including medications for opioid use disorder (MOUD) following an opioid overdose reversal with the long-acting opioid antagonist nalmefene HCl injection vs. short-acting opioid antagonist naloxone. |
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Methods |
Observational cohort study of patients who accept addiction services following an opioid overdose reversal in the ED. |
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Key Outcome Variables |
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Basic Research Requirements |
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INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR NALMEFENE HYDROCHLORIDE INJECTION AND ZURNAI (NALMEFENE INJECTION) AUTO-INJECTOR
Nalmefene Hydrochloride Injection
INDICATIONS AND USAGE
Nalmefene Hydrochloride Injection is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids.
Nalmefene Hydrochloride Injection is indicated in the management of known or suspected opioid overdose.
IMPORTANT SAFETY INFORMATION
Contraindications
Nalmefene Hydrochloride injection is contraindicated in patients with a known hypersensitivity to the product.
WARNINGS AND PRECAUTIONS
Use of Nalmefene Hydrochloride injection in Emergencies
Nalmefene Hydrochloride injection, like all drugs in this class, is not the primary treatment for ventilatory failure. In most emergency settings, treatment with Nalmefene Hydrochloride injection should follow, not precede, the establishment of a patent airway, ventilatory assistance, administration of oxygen, and establishment of circulatory access.
Risk of Recurrent Respiratory Depression
Accidental overdose with long acting opioids [such as methadone and levo-alpha-acetylmethadol (LAAM)] may result in prolonged respiratory depression. Respiratory depression in both the postoperative and overdose setting may be complex and involve the effects of anesthetic agents, neuromuscular blockers, and other drugs. While Nalmefene Hydrochloride injection has a longer duration of action than naloxone in fully reversing doses, the physician should be aware that a recurrence of respiratory depression is possible, even after an apparently adequate initial response to Nalmefene Hydrochloride injection treatment.
Patients treated with Nalmefene Hydrochloride injection should be observed until, in the opinion of the physician, there is no reasonable risk of recurrent respiratory depression.
Cardiovascular Risks with Narcotic Antagonists
Pulmonary edema, cardiovascular instability, hypotension, hypertension, ventricular tachycardia, and ventricular fibrillation have been reported in connection with opioid reversal in both postoperative and emergency department settings. In many cases, these effects appear to be the result of abrupt reversal of opioid effects.
Although Nalmefene Hydrochloride injection has been used safely in patients with pre-existing cardiac disease, all drugs of this class should be used with caution in patients at high cardiovascular risk or who have received potentially cardiotoxic drugs.
Risk of Precipitated Withdrawal
Nalmefene Hydrochloride injection, like other opioid antagonists, is known to produce acute withdrawal symptoms and, therefore, should be used with extreme caution in patients with known physical dependence on opioids or following surgery involving high doses of opioids.
Imprudent use or excessive doses of opioid antagonists in the postoperative setting has been associated with hypertension, tachycardia, and excessive mortality in patients at high risk for cardiovascular complications.
Incomplete Reversal of Buprenorphine
Preclinical studies have shown that nalmefene at doses up to 10 mg/kg (437 times the maximum recommended human dose) produced incomplete reversal of buprenorphine-induced analgesia in animal models. This appears to be a consequence of a high affinity and slow displacement of buprenorphine from the opioid receptors. Hence, Nalmefene Hydrochloride injection may not completely reverse buprenorphine-induced respiratory depression.
Use in Pediatric Patients
Safety and effectiveness of Nalmefene Hydrochloride Injection in pediatric patients have not been established.
ADVERSE REACTIONS
The most common adverse reactions (>1%) reported in clinical trials with nalmefene injection were nausea (18%), vomiting (9%), tachycardia (5%), hypertension (5%), postoperative pain (4%), fever (3%), and dizziness (3%).
Please read Full Prescribing Information here.
To report SUSPECTED ADVERSE REACTIONS, contact Knoa Pharma LLC at 1-888-726-7535, option 2, or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
ZURNAI (nalmefene injection) Auto-Injector
INDICATIONS AND USAGE
ZURNAI is indicated for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression.
ZURNAI is intended for immediate administration as emergency therapy in settings where opioids may be present.
ZURNAI is not a substitute for emergency medical care.
IMPORTANT SAFETY INFORMATION
Contraindications
ZURNAI is contraindicated in patients known to be hypersensitive to nalmefene hydrochloride or to any other ingredients in the product.
WARNINGS AND PRECAUTIONS
Risk of Recurrent Respiratory and Central Nervous System Depression
A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI if necessary, using a new auto-injector with each dose while awaiting emergency medical assistance.
Risk of Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists
Reversal of respiratory depression by partial agonists or mixed agonists/antagonists such as buprenorphine and pentazocine, may be incomplete. Repeat doses of ZURNAI may be required.
Precipitation of Severe Opioid Withdrawal
The use of ZURNAI in patients who are opioid dependent may precipitate opioid withdrawal.
Abrupt postoperative reversal of opioid depression may result in adverse cardiovascular (CV) effects. These events have primarily occurred in patients who had preexisting CV disorders or received other drugs that may have similar adverse CV effects. Monitor these patients closely in an appropriate healthcare setting after use of ZURNAI.
In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. Monitor the patient for the development of the signs and symptoms of opioid withdrawal.
Risk of Opioid Overdose from Attempts to Overcome the Blockade
Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may lead to opioid intoxication and death.
ADVERSE REACTIONS
Most common adverse reactions (> 5%) are feeling hot, nausea, headache, dizziness, chills, vomiting, allodynia, palpitations, tinnitus, ear discomfort, feeling abnormal, burning sensation, hot flush, and irritability.
USE IN SPECIFIC POPULATIONS
Pregnancy
An opioid overdose is a medical emergency and can be fatal for the pregnant woman and fetus if left untreated. Treatment with ZURNAI for opioid overdose should not be withheld because of potential concerns regarding the effects of ZURNAI in the fetus.
Pediatric Use
The safety and effectiveness of ZURNAI for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, have not been established in pediatric patients younger than 12 years of age.
Geriatric Use
Clinical studies of nalmefene hydrochloride injection did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Please read Full Prescribing Information.
To report SUSPECTED ADVERSE REACTIONS, contact Knoa Pharma LLC at 1-888-726-7535, option 2, or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
Intended for healthcare professionals of the United States of America only.
References:
- Nalmefene HCl Injection Full Prescribing Information. Stamford, CT: Knoa Pharma LLC.
- Zurnai (nalmefene injection) Auto-Injector Full Prescribing Information. Stamford, CT: Knoa Pharma LLC.