What side effects are associated with this type of intervention?

Common treatments for acute pain, such as hydrocodone and other opioids, are associated with several side effects. These include constipation, nausea, vomiting, sedation, impaired psychomotor function, and urinary retention. There is also a risk of respiratory depression, particularly when combined with other central nervous system depressants like benzodiazepines or alcohol. The O2P Hydrocodone Prodrugs (ETR028 and ETR029) are designed to reduce the risk of overdose by modifying the release and absorption of hydrocodone, potentially mitigating some of these risks.

What prior FDA approvals exist?

The FDA has approved several opioid medications for the treatment of acute pain, including hydrocodone, oxycodone, and morphine. These medications are often formulated to manage pain effectively while minimizing the risk of abuse and overdose. For instance, extended-release formulations like OROS® hydromorphone and sustained-release oxycodone have been developed to provide consistent pain relief with reduced dosing frequency. The O2P Hydrocodone Prodrugs (ETR028 and ETR029) are designed to further enhance safety by modifying the release and absorption of hydrocodone, aiming to lower the risk of overdose. These advancements reflect ongoing efforts to balance effective pain management with the need to mitigate opioid-related risks.

What other types of research exist?

Promising alternatives to O2P Hydrocodone Prodrugs for acute pain management include: 1) Extended-release hydromorphone, which has shown efficacy and safety in cancer pain management and may offer benefits in acute pain settings. 2) Abuse-deterrent formulations of oxycodone, which have been designed to reduce misuse and overdose risks. 3) Buprenorphine, particularly in its sublingual or transdermal forms, which provides effective pain relief with a ceiling effect on respiratory depression, reducing overdose risk.

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Opioid Analgesic

ETR028 + ETR029 for Acute Pain

Q: What is the mechanism of action of this treatment?

Opioids, such as hydrocodone, are commonly used to treat acute pain by binding to opioid receptors in the brain and spinal cord, thereby reducing the perception of pain. Hydrocodone is metabolized into hydromorphone, which provides the analgesic effect. The O2P Hydrocodone Prodrugs (ETR028 and ETR029) are designed to modify the release and absorption of hydrocodone, reducing the risk of overdose by preventing rapid spikes in drug levels. This approach is crucial for acute pain patients as it aims to deliver effective pain relief while minimizing the potential for misuse and adverse effects.

Phase 1

Recruiting

Led By Leela Vrishabhendra, MD

Research Sponsored by Elysium Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must be male or female, 18 to 55 years of age, at the Screening Visit

Subjects must have an estimated glomerular filtration rate (eGFR) of >= 60 mL/min/1.73 m2 at the Screening Visit

Must not have

Subjects with a clinically significant history or presence of gastrointestinal pathology or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug

Subjects with clinically relevant abnormal physical findings, ECG, or laboratory values at or during the Screening Visit

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time zero (just prior to dose) to 48 hours post dose timepoints: pre-dose and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests new, safer forms of hydrocodone in healthy adults to see how safe they are and how the body processes them. The new drugs are designed to reduce overdose risk by limiting how much the body can absorb. Hydrocodone has been reclassified as a more controlled substance to reduce prescription drug abuse.

Who is the study for?

Healthy adults aged 18-55, with a BMI of 18-32 kg/m2 and good overall health are eligible for this trial. They must have previously tolerated opioids, have normal kidney function and blood tests, agree to contraception rules if applicable, and follow study procedures including eating a high-fat meal.

What is being tested?

The trial is testing the safety and how the body processes two new hydrocodone drugs (ETR028 & ETR029) compared to an existing drug (HCBT). Participants will take single doses under different conditions (with or without food) while also taking naltrexone to block opioid effects.

What are the potential side effects?

Possible side effects may include typical opioid-related issues such as nausea, vomiting, constipation, drowsiness or dizziness. Since it's a Phase 1 trial focused on healthy individuals, detailed side effect profiles will be determined during the study.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 55 years old.

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My kidney function, measured by eGFR, is 60 mL/min/1.73 m2 or higher.

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I am following the required contraception guidelines.

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I have taken prescription opioids before without severe side effects.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I don't have stomach or intestine problems affecting drug absorption.

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I have abnormal test results or physical findings from my screening visit.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time zero (just prior to dose) to 48 hours post dose timepoints: pre-dose and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time zero (just prior to dose) to 48 hours post dose timepoints: pre-dose and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose.

This trial's timeline: 3 weeks for screening, Varies for treatment, and time zero (just prior to dose) to 48 hours post dose timepoints: pre-dose and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours post-dose. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pyruvate Kinase

Subjects reporting at least one Adverse Event (AE)

Subjects reporting at least one Serious Adverse Event (SAE)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

17Treatment groups

Experimental Treatment

Active Control

Group I: B6. [ETR028 + ETR029] blend "1", "2", "3", or "4"Experimental Treatment1 Intervention

8-fold higher dose of \[ETR028 + ETR029\] blend "1", "2", "3", or "4" single oral dose (fed)

Group II: B5. [ETR028 + ETR029] blend "1", "2", "3", or "4"Experimental Treatment1 Intervention

8-fold higher dose of \[ETR028 + ETR029\] blend "1", "2", "3", or "4" single oral dose (fasted)

Group III: B4. [ETR028 + ETR029] blend "1", "2", "3", or "4"Experimental Treatment1 Intervention

4-fold higher dose of \[ETR028 + ETR029\] blend "1", "2", "3", or "4" single oral dose (fasted)

Group IV: B3. [ETR028 + ETR029] blend "1", "2", "3", or "4" (fed)Experimental Treatment1 Intervention

\[ETR028 - dose TBD + ETR029 - \<=30mg\] single oral dose (fed)

Group V: B3. [ETR028 + ETR029] blend "1", "2", "3", or "4" (fasted)Experimental Treatment1 Intervention

2-fold higher dose of \[ETR028 + ETR029\] blend "1", "2", "3", or "4" single oral dose (fasted)

Group VI: B2. [ETR028 + ETR029] blend "4"Experimental Treatment1 Intervention

\[ETR028 - dose TBD + ETR029 - \<=30mg\] single oral dose (fasted)

Group VII: B2. [ETR028 + ETR029] blend "3"Experimental Treatment1 Intervention

\[ETR028 - dose TBD + ETR029 - \<=30mg\] single oral dose (fasted)

Group VIII: B1. [ETR028 + ETR029] blend "2"Experimental Treatment1 Intervention

\[ETR028 - dose TBD + ETR029 - \<=30mg\] single oral dose (fasted)

Group IX: B1. [ETR028 + ETR029] blend "1"Experimental Treatment1 Intervention

\[ETR028 - dose To Be Determined (TBD) + ETR029 - \<=30mg\] single oral dose (fasted)

Group X: A2. <=60mg ETR028Experimental Treatment1 Intervention

\<=60 mg ETR028 single oral dose (fasted)

Group XI: A1.2. 30 mg ETR029Experimental Treatment1 Intervention

30 mg ETR029 single oral dose (fasted)

Group XII: A1.2. 30 mg ETR028Experimental Treatment1 Intervention

30 mg ETR028 single oral dose (fasted)

Group XIII: A1.1. 30 mg ETR029 SentinelExperimental Treatment1 Intervention

30 mg ETR029 single oral dose (fasted)

Group XIV: A1.1. 30 mg ETR028 SentinelExperimental Treatment1 Intervention

30 mg ETR028 single oral dose (fasted)

Group XV: A2. <= 80mg HCBTActive Control1 Intervention

\<= 80mg HCBT single oral dose (fasted)

Group XVI: A1.1. 5 mg HCBTActive Control1 Intervention

5 mg hydrocodone bitartrate (HCBT) single oral dose (fasted)

Group XVII: A1.1. 10 mg HCBTActive Control1 Intervention

10 mg HCBT single oral dose (fasted)

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Opioids, such as hydrocodone, are commonly used to treat acute pain by binding to opioid receptors in the brain and spinal cord, thereby reducing the perception of pain. Hydrocodone is metabolized into hydromorphone, which provides the analgesic effect. The O2P Hydrocodone Prodrugs (ETR028 and ETR029) are designed to modify the release and absorption of hydrocodone, reducing the risk of overdose by preventing rapid spikes in drug levels. This approach is crucial for acute pain patients as it aims to deliver effective pain relief while minimizing the potential for misuse and adverse effects.

A fixed nitrous oxide/oxygen mixture as an analgesic for trauma patients in emergency department: study protocol for a randomized, controlled trial.The landscape of pain management in people with dementia living in care homes: a mixed methods study.Analgesic Prodrugs for Combating their Side-Effects: Rational Approach.