Research

 Green background with white lines on left side

Deepening Learning and Collaboration to Address the Evolving Opioid Crisis

Knoa Pharma supports research through two pathways: investigator-initiated research (IIR), in which independent investigators propose and conduct studies, and collaborative research, in which our Medical Affairs team works with external researchers to address shared scientific questions. 

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. 

There is limited data on the use of nalmefene HCl injection in today’s opioid overdose environment. Outcomes associated with the use of nalmefene HCl injection are of particular interest. 

Investigator Initiated Research

We support IIRs through a competitive Request for Proposal (RFP) process. The current funding cycle is now open. Researchers interested in opioid overdose reversal and management are encouraged to submit proposals. Additional information on submission requirements and deadlines is available here. Topline details regarding the current funding opportunity are provided below. 

Evaluating injectable nalmefene as an alternative for continuous naloxone infusions in hospital settings

Objectives

To evaluate the use of nalmefene HCl injection as an alternative or in comparison to the use of continuous naloxone infusion for the treatment of opioid overdose

Key Outcome Variables of Interest

  • Patient outcomes
  • Treatment characteristics
  • Safety
  • Hospital admission rates
  • Resource utilization

Collaborative Research Initiatives

Knoa Pharma’s Medical Affairs Department is interested in conducting collaborative research with nalmefene injection in the emergency department and/or pre-hospital setting for the reversal of opioid overdose.  

Below is a high-level summary of each of our research initiatives.  Interested research collaborators should reach out to their Medical Science Liaison (MSL), email: medicalaffairs@pharma.com, or call 1-888-726-7535, option 1 for discussions or questions.

Recently Completed Research

Clinical Outcomes from Injectable Nalmefene in the Emergency Department

Study Location

UC San Diego Health and El Centro Regional Medical Center (California)

Objectives

To assess the utilization of nalmefene HCl injection for the treatment of known or suspected acute opioid overdose in the ED setting; and the dosage(s) associated with those reversals

Methods

Retrospective observational study of electronic health records (EHR)

Key Outcome Variables

  • Patient outcomes (e.g., hospital admission, discharge, frequency of multiple antagonist administrations)
  • Nalmefene dosages administered
  • Naloxone dosages administered (including any pre-hospital administrations)
  • Frequency of precipitated withdrawal symptoms

https://www.businesswire.com/news/home/20240930742710/en/Study-Examining-Use-of-Nalmefene-HCI-Injection-for-Opioid-Overdose-Reversal-in-Emergency-Departments-Concludes-Observational-Period

Attitudes Toward use of Auto-Injectors During a Medical Emergency

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.

Methods

Surveys of general U.S. population, including people with an increased likelihood of providing emergency resuscitation during an opioid overdose.

Key Outcome Variables

  • Willingness and comfort-level using auto-injectors and nasal sprays
  • Attitudes toward using these devices with loved ones, colleagues and strangers

2025 ASHP Midyear Clinical Meeting Poster Abstracts, American Journal of Health-System Pharmacy, Volume 83, Issue Supplement_2, 6 March 2026, Pages S1–S2907, https://doi.org/10.1093/ajhp/zxaf258

Research Studies Currently In-Progress

Use of Naloxone Infusion to Treat Opioid Overdose in Hospital Settings

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.

Methods

Retrospective evaluation of electronic health records (EHR)

Key Outcome Variables

  • Frequency of naloxone infusion
  • Length (time) of infusion, infusion rate, and total dose administered
  • Patient outcomes (e.g., recurrence of respiratory depression, hospital admission, discharge)
  • Opioids known or suspected to have contributed to the overdose

Current Research Interests

Patient Outcomes Following Administration of nalmefene HCI injection for Treatment of Opioid Overdose

Objectives

To assess the reversal of respiratory depression following the administration of nalmefene HCl injection in hospital or EMS settings.

Methods

Observational cohort study of patients who are administered nalmefene HCl injections as part of treatment for a known or suspected opioid overdose.

Key Outcome Variables

  • Patient outcomes (e.g., opioid reversal, recurrence of respiratory depression)
  • Antagonist dosages administered (including any use of naloxone)
  • Presence of precipitated withdrawal, and any treatments administered to address withdrawal symptoms
  • Resource utilization (e.g., hospital admission, observation time, discharge, patient comorbidities, EMS transport)
  • Opioids known or suspected to have contributed to the overdose

Basic Research Requirements

  • Nalmefene HCl injection on formulary and available to hospital and/or EMS personnel

Evaluate Patient Acceptance of Addiction Services following Opioid Overdose Reversal Treatment

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.

Methods

Observational cohort study of patients who accept addiction services following an opioid overdose reversal in the ED.

Key Outcome Variables

  • Likelihood of accepting addiction services while in the ED
  • Factors such as demographics and clinical characteristics that contribute to accepting addiction services

Basic Research Requirements

  • Nalmefene HCl injection on formulary and available to ED personnel

Comparison of Nalmefene Injection vs Naloxone for Sustained Opioid Overdose Reversal During Prolonged EMS Transport 

Objectives

To determine whether nalmefene reduces recurrent opioid overdose during prolonged transport compared to naloxone, along with assessing patient stability.

Methods

  • Observational, non-interventional study of current nalmefene and naloxone use
  • Data abstracted from electronic patient care records and/or pre-hospital care reports

Key Outcome Variables

  • Recurrence of respiratory depression before arrival to emergency department
  • Frequency of multiple antagonist administrations (e.g., need for repeat dosing)
  • Dosages administered for nalmefene and naloxone
  • Operational impact (e.g., on-scene time, total transport time, level of care necessary during transport)
  • Patient care optimization
  • Frequency of adverse events (e.g., including precipitated withdrawal symptoms)

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.

Opioid Overdose Reversal Publications

To learn more about Knoa Pharma’s published research on medicines for opioid overdose reversal, click here.

References:

  1. Nalmefene HCl Injection Full Prescribing Information. Stamford, CT: Knoa Pharma LLC.
  2. Zurnai (nalmefene injection) Auto-Injector Full Prescribing Information. Stamford, CT: Knoa Pharma LLC.
×