CLINICAL TRIALS PROFILE FOR NALOXONE

505(b)(2) Clinical Trials for NALOXONE

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	NCT02137213 ↗	Feasibility Study of Oral Naloxone for Treatment of Methadone-induced Constipation	Completed	Academic Health Science Centres	Phase 2	2014-08-01	At least 30% of patients receiving methadone maintenance therapy (MMT) are suffering from constipation that often affects effectiveness of MMT and increases its impact on health care system. Existing treatments include several over-the-counter medications which do not target the pathobiological basis of opioid-induced constipation and have limited effectiveness. At the same time well-known medication, naloxone, was already shown to help with constipation in patients receiving methadone for chronic pain, but was never tried in patients receiving methadone for opioid dependence. This study is aimed to try naloxone for treatment of opioid-induced constipation in MMT settings. The investigators will enroll 20 patients receiving MMT and suffering from opioid-induced constipation. The study has a crossover design - all patients will receive one week of their regular methadone doses and one week of their regular methadone doses with naloxone added. Normal saline will be added to methadone-only formulations as placebo. Order of the weeks will be chosen randomly. Both subjects and investigators will be blinded to the study condition (i.e. whether naloxone or normal saline is added to methadone preparation on a given week). Primary hypothesis: Patients receiving combination of oral methadone/naloxone in ratio 50:1 will have less severe symptoms of constipation compared to those receiving methadone only. Secondary hypothesis: Addition of oral naloxone to methadone in a ratio 50:1 will not cause clinically significant opioid withdrawal symptoms.
OTC	NCT02137213 ↗	Feasibility Study of Oral Naloxone for Treatment of Methadone-induced Constipation	Completed	Centre for Addiction and Mental Health	Phase 2	2014-08-01	At least 30% of patients receiving methadone maintenance therapy (MMT) are suffering from constipation that often affects effectiveness of MMT and increases its impact on health care system. Existing treatments include several over-the-counter medications which do not target the pathobiological basis of opioid-induced constipation and have limited effectiveness. At the same time well-known medication, naloxone, was already shown to help with constipation in patients receiving methadone for chronic pain, but was never tried in patients receiving methadone for opioid dependence. This study is aimed to try naloxone for treatment of opioid-induced constipation in MMT settings. The investigators will enroll 20 patients receiving MMT and suffering from opioid-induced constipation. The study has a crossover design - all patients will receive one week of their regular methadone doses and one week of their regular methadone doses with naloxone added. Normal saline will be added to methadone-only formulations as placebo. Order of the weeks will be chosen randomly. Both subjects and investigators will be blinded to the study condition (i.e. whether naloxone or normal saline is added to methadone preparation on a given week). Primary hypothesis: Patients receiving combination of oral methadone/naloxone in ratio 50:1 will have less severe symptoms of constipation compared to those receiving methadone only. Secondary hypothesis: Addition of oral naloxone to methadone in a ratio 50:1 will not cause clinically significant opioid withdrawal symptoms.
New Formulation	NCT02158117 ↗	Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use	Completed	St. Olavs Hospital	Phase 1	2014-03-01	Overdose with potential deadly outcome is a serious problem among opioid abusers, not least in Norway. The annual death toll from overdose is about 250, twice the annual death toll from traffic accidents. Those who inject heroin or other opioids are considered to have the highest risk for death from overdose. To save lives, immediate treatment with a μ-opioid antidote such as naloxone is required. Usually naloxone is injected into a muscle or a blood vessel. Administration of naloxone via the nose has been suggested as an alternative for use by emergency teams and possibly also bystanders. This is not only an easier way to give naloxone, but would also eliminate the risk for needle stick injuries and blood contamination. A pilot study in this hospital has shown no significant side effects or adverse reaction. While significant benefits are expected from developing an adequately formulated naloxone nasal spray for pre-hospital use, the risks to participants are minimal. Therefore this preclinical study in healthy volunteers will be undertaken.
New Formulation	NCT02158117 ↗	Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use	Completed	Norwegian University of Science and Technology	Phase 1	2014-03-01	Overdose with potential deadly outcome is a serious problem among opioid abusers, not least in Norway. The annual death toll from overdose is about 250, twice the annual death toll from traffic accidents. Those who inject heroin or other opioids are considered to have the highest risk for death from overdose. To save lives, immediate treatment with a μ-opioid antidote such as naloxone is required. Usually naloxone is injected into a muscle or a blood vessel. Administration of naloxone via the nose has been suggested as an alternative for use by emergency teams and possibly also bystanders. This is not only an easier way to give naloxone, but would also eliminate the risk for needle stick injuries and blood contamination. A pilot study in this hospital has shown no significant side effects or adverse reaction. While significant benefits are expected from developing an adequately formulated naloxone nasal spray for pre-hospital use, the risks to participants are minimal. Therefore this preclinical study in healthy volunteers will be undertaken.
New Formulation	NCT00637000 ↗	Induction of Opioid-Dependent Individuals Onto Buprenorphine and Buprenorphine/Naloxone	Completed	Indivior Inc.	Phase 2	2008-03-01	The purpose of this study is to compare the presence, degree, time course and profile of opioid withdrawal symptoms associated with induction onto new formulations of buprenorphine or buprenorphine/naloxone in persons with active opioid dependence. The primary outcome measure is the severity of withdrawal symptoms measured using the Clinical Opiate Withdrawal Scale (COWS). The primary study hypothesis is that neither drug formulation will precipitate an opioid withdrawal syndrome.

All Clinical Trials for NALOXONE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000192 ↗	Neurobiology of Opioid Dependence: 1 - 1	Withdrawn	National Institute on Drug Abuse (NIDA)	Phase 2	1993-01-01	The purpose of this study is to evaluate the effects of lamotrigine on naloxone-precipitated opiate withdrawal.
NCT00000192 ↗	Neurobiology of Opioid Dependence: 1 - 1	Withdrawn	Yale University	Phase 2	1993-01-01	The purpose of this study is to evaluate the effects of lamotrigine on naloxone-precipitated opiate withdrawal.
NCT00000193 ↗	Neurobiology of Opioid Dependence: 2 - 2	Withdrawn	National Institute on Drug Abuse (NIDA)	Phase 2	1993-01-01	The purpose of this study is to evaluate the effects of gamma hydroxybutyric on naloxone-precipitated opiate withdrawal.
NCT00000193 ↗	Neurobiology of Opioid Dependence: 2 - 2	Withdrawn	Yale University	Phase 2	1993-01-01	The purpose of this study is to evaluate the effects of gamma hydroxybutyric on naloxone-precipitated opiate withdrawal.
NCT00000194 ↗	Neurobiology of Opioid Dependence: 3 - 3	Withdrawn	National Institute on Drug Abuse (NIDA)	Phase 2	1993-01-01	The purpose of this study is to study the effects of cycloserine on naloxone-precipitated opiate withdrawal.

Clinical Trial Conditions for NALOXONE

Condition Name

Condition Name for NALOXONE
Intervention	Trials
Opioid-Related Disorders	40
Pain	29
Opioid Use Disorder	23
Opioid Dependence	21

Condition MeSH

Condition MeSH for NALOXONE
Intervention	Trials
Opioid-Related Disorders	125
Substance-Related Disorders	35
Disease	20
Constipation	18

Clinical Trial Locations for NALOXONE

Trials by Country

+

−

Trials by Country for NALOXONE
Location	Trials
United States	467
Canada	23
China	22
Norway	14
Germany	12

Trials by US State

+

−

Trials by US State for NALOXONE
Location	Trials
New York	42
Maryland	36
California	32
Massachusetts	22
Pennsylvania	19

Clinical Trial Progress for NALOXONE

Clinical Trial Phase

Clinical Trial Phase for NALOXONE
Clinical Trial Phase	Trials
Phase 4	85
Phase 3	55
Phase 2/Phase 3	11

Clinical Trial Status

Clinical Trial Status for NALOXONE
Clinical Trial Phase	Trials
Completed	206
Recruiting	42
Not yet recruiting	39

Clinical Trial Sponsors for NALOXONE

Sponsor Name

Sponsor Name for NALOXONE
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	66
Indivior Inc.	14
Johns Hopkins University	13

Sponsor Type

Sponsor Type for NALOXONE
Sponsor	Trials
Other	340
Industry	124
NIH	79

NALOXONE: Clinical Trials, Market Analysis, and Projections

Introduction to Naloxone

Naloxone is a life-saving medication used to reverse opioid overdoses by counteracting the effects of opioids on the brain. Its importance has grown significantly due to the escalating opioid epidemic. Here, we will delve into the current clinical trials, market analysis, and projections for naloxone.

Clinical Trials and Efficacy

Opioid Associated Out of Hospital Cardiac Arrest (NOPACA)

A significant clinical trial underway is the NOPACA (Naloxone for Opioid Associated Out of Hospital Cardiac Arrest) study. This randomized, double-blind, controlled trial aims to determine the efficacy of naloxone versus a placebo in patients experiencing opioid-associated out-of-hospital cardiac arrest (OA-OHCA)[4].

• Objective: To assess whether early administration of naloxone by emergency medical services (EMS) improves survival and neurological outcomes in patients with OA-OHCA.
• Methodology: The trial involves administering 2mg of naloxone via IV or IO route immediately after the first dose of epinephrine. The control group receives saline.
• Outcomes: The study will measure sustained return of spontaneous circulation (ROSC), survival to hospital discharge, and neurological outcomes using the modified Rankin Scale.
• Feasibility: The pilot phase will determine the feasibility of enrolling and randomizing participants, treatment fidelity, and retention rates.

This trial addresses a critical knowledge gap and has the potential to save thousands of lives annually in the context of the worsening opioid epidemic.

Community-Based Naloxone Distribution

Another crucial aspect of naloxone's clinical impact is its distribution strategies. Studies have shown that increasing naloxone availability and the probability of witnessed overdoses can significantly reduce opioid overdose deaths (OODs).

• Distribution Strategies: Modeling results indicate that distributing more naloxone, supported by opioid settlement funds, could reduce OODs by 6.3% to 8.8% in 2025, depending on the distribution approach (supply-based or demand-based)[1].
• Witnessed Overdoses: Increasing the probability of witnessed overdoses by 20% to 60% could further reduce OODs, with the most significant reduction seen when combining increased naloxone distribution with a 60% increase in witnessed overdoses, potentially reducing OODs by 33.5% to 37.4% in 2025[1].

Market Analysis and Projections

Global Market Growth

The naloxone spray market is experiencing rapid growth driven by the increasing prevalence of opioid overdoses and growing awareness of naloxone's life-saving potential.

• Market Size: The global naloxone spray market is projected to grow from $285.09 million in 2020 to $785.35 million by 2025, at a compound annual growth rate (CAGR) of 22.3%[2].
• Segmentation: The market is segmented by application (hospitals, EMS, pharmacies) and type (0.4 mg/mL and 1 mg/mL spray devices). The EMS segment is expected to dominate due to the widespread use of naloxone in emergency situations[5].

Regional Market

North America is anticipated to hold a significant market share due to the high prevalence of opioid overdoses and the availability of advanced healthcare infrastructure in the region[5].

Key Players

Major players in the naloxone market include Teva Pharmaceutical Industries Ltd. and Emergent BioSolutions Inc. These companies are driving innovation and accessibility of naloxone products[5].

Forms of Naloxone

Naloxone is available in several forms, each with its own advantages and uses:

• Injection Formulations: Historically the most common form, often used in non-retail settings such as hospitals and clinics[3].
• Auto-Injectors: Designed for ease of use, particularly beneficial for laypersons.
• Nasal Sprays: The most user-friendly form, which has seen significant growth and is expected to continue dominating the market due to its lower cost and availability as a generic medication[3][5].

Regulatory Considerations

The FDA is considering converting individual naloxone products to over-the-counter (OTC) status, which could further expand access to this critical medication[3].

Cost-Effectiveness and Accessibility

The cost-effectiveness of naloxone distribution strategies is a key consideration. Studies have shown that making naloxone available to people most likely to observe an opioid overdose can be highly effective in reducing overdose fatalities. The goal is to make naloxone accessible beyond healthcare providers, reaching at-risk individuals, their social networks, and communities[3].

Public Health Impact

The public health impact of naloxone is substantial. By reducing the ratio of fatal to nonfatal opioid overdoses, naloxone distribution strategies contribute significantly to lowering opioid overdose mortality. For instance, a combination of increased naloxone distribution and a 60% increase in witnessed overdoses could result in the lowest ratio of fatal to nonfatal opioid overdoses, indicating a significant reduction in fatality risk per overdose[1].

"Compared with the status quo naloxone and baseline probability of witnessed overdoses, the combination (with the probability of witnessed overdoses increased by 60%) could avert as many as 129 (95% SI, 63-190; relative reduction, 33.5%; 95% SI, 17.1%-50.4%) and 144 (95% SI, 74-206; relative reduction, 37.4%; 95% SI, 19.6%-56.3%) OODs in 2025 with supply-based and demand-based distribution approaches." - *Source: JAMA Network Open*[1]

Key Takeaways

• Clinical Trials: Ongoing trials like NOPACA are crucial for understanding the efficacy of naloxone in specific scenarios such as out-of-hospital cardiac arrests.
• Market Growth: The naloxone spray market is expected to grow significantly, driven by the increasing prevalence of opioid overdoses and government initiatives.
• Distribution Strategies: Combining increased naloxone distribution with interventions to increase witnessed overdoses can significantly reduce opioid overdose deaths.
• Accessibility: Efforts to make naloxone available over-the-counter and expand its distribution beyond healthcare settings are vital for public health impact.
• Forms of Naloxone: Nasal sprays are becoming increasingly popular due to their ease of use and lower cost.

FAQs

What is the primary use of naloxone?

Naloxone is used to reverse opioid overdoses by counteracting the effects of opioids on the brain.

How is the naloxone market expected to grow?

The global naloxone spray market is expected to reach $785.35 million by 2025, growing at a CAGR of 22.3% from 2020 to 2025.

What forms of naloxone are available?

Naloxone is available in injection formulations, auto-injectors, and nasal sprays.

What is the NOPACA trial?

The NOPACA trial is a clinical study aimed at determining the efficacy of naloxone versus a placebo in patients experiencing opioid-associated out-of-hospital cardiac arrest.

How effective is naloxone in reducing opioid overdose deaths?

Studies indicate that combining increased naloxone distribution with interventions to increase witnessed overdoses can reduce opioid overdose deaths by up to 37.4% in certain scenarios.

Sources

1. JAMA Network Open: "Evaluation of Strategies to Enhance Community-Based Naloxone Distribution to Reduce Opioid Overdose Deaths"[1].
2. EIN Presswire: "Naloxone Spray Global Market To Grow At Rate Of 22% Through 2025"[2].
3. LDI at Penn: "Expanding Access to Naloxone: A Review of Distribution Strategies"[3].
4. UCSF Clinical Trials: "Naloxone for Opioid Associated Out of Hospital Cardiac Arrest"[4].
5. Data Insights Market: "Naloxone Spray 2025 to Grow at XX CAGR with XXX million Market"[5].