Evaluate the Safety and Pharmacokinetic Profile of ETR028 and ETR029 in Healthy Adult Subjects

NCT05572190 | Unknown Phase 1 FDA Drug

• 2 other identifiers: O2P-001R01DA046102
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this Phase 1 clinical study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of O2P (Oral Overdose Protected) hydrocodone prodrugs (ETR028 and ETR029) relative to hydrocodone bitartrate hemipentahydrate (HCBT) comparator following single oral doses in healthy adult subjects under fasted and fed conditions with naltrexone blockade

Conditions

Acute Pain

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic (PK) profile

  Plasma concentration-time profile (ng/ml) of ETR028, ETR029, \[ETR028 + ETR029\] blend, O2P hydrocodone-derived 3 major metabolites (e.g., 3-hydroxy-arylguanadine \[3-HAG\], 4-hydroxy-arylguanadine \[4-HAG\], and ETR106), and hydrocodone

  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.

• Subjects reporting at least one Adverse Event (AE)

  An AE can be any unfavorable and/or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the investigational medicinal product, whether or not related to the investigational medicinal product.

  From the time a subject is dosed until 8 day post-dose Follow-Up Visit

• Subjects reporting at least one Serious Adverse Event (SAE)

  A Serious Adverse Event is an AE that results in any of the following outcomes; Death, Life-threatening, inpatient hospitalization or causes prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical event (i.e., based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent 1 of the outcomes listed above)

  From the time a subject is dosed up to 30 days post-dose

Study Arms (17)

A1.1. 30 mg ETR028 Sentinel

EXPERIMENTAL

30 mg ETR028 single oral dose (fasted)

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A1.1. 30 mg ETR029 Sentinel

EXPERIMENTAL

30 mg ETR029 single oral dose (fasted)

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A1.1. 5 mg HCBT

ACTIVE COMPARATOR

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A1.1. 10 mg HCBT

ACTIVE COMPARATOR

10 mg HCBT single oral dose (fasted)

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A1.2. 30 mg ETR028

EXPERIMENTAL

30 mg ETR028 single oral dose (fasted)

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A1.2. 30 mg ETR029

EXPERIMENTAL

30 mg ETR029 single oral dose (fasted)

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A2. <=60mg ETR028

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

A2. <= 80mg HCBT

ACTIVE COMPARATOR

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B1. [ETR028 + ETR029] blend "1"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B1. [ETR028 + ETR029] blend "2"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B2. [ETR028 + ETR029] blend "3"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B2. [ETR028 + ETR029] blend "4"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B3. [ETR028 + ETR029] blend "1", "2", "3", or "4" (fed)

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B3. [ETR028 + ETR029] blend "1", "2", "3", or "4" (fasted)

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B4. [ETR028 + ETR029] blend "1", "2", "3", or "4"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B5. [ETR028 + ETR029] blend "1", "2", "3", or "4"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

B6. [ETR028 + ETR029] blend "1", "2", "3", or "4"

EXPERIMENTAL

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

Drug: ETR028, ETR029, [ETR028 + ETR029] or HCBT

Interventions

ETR028, ETR029, [ETR028 + ETR029] or HCBT DRUG

Hydrocodone prodrugs

Also known as: O2P hydrocodone

A1.1. 10 mg HCBT; A1.1. 30 mg ETR028 Sentinel; A1.1. 30 mg ETR029 Sentinel; A1.1. 5 mg HCBT; A1.2. 30 mg ETR028; A1.2. 30 mg ETR029; A2. <= 80mg HCBT; A2. <=60mg ETR028; B1. [ETR028 + ETR029] blend "1"; B1. [ETR028 + ETR029] blend "2"; B2. [ETR028 + ETR029] blend "3"; B2. [ETR028 + ETR029] blend "4"; B3. [ETR028 + ETR029] blend "1", "2", "3", or "4" (fasted); B3. [ETR028 + ETR029] blend "1", "2", "3", or "4" (fed); B4. [ETR028 + ETR029] blend "1", "2", "3", or "4"; B5. [ETR028 + ETR029] blend "1", "2", "3", or "4"; B6. [ETR028 + ETR029] blend "1", "2", "3", or "4"

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be male or female, 18 to 55 years of age, inclusive, at the Screening Visit;
• Subjects must be willing and able to give written informed consent for participation in the study prior to the initiation of any screening or study-specific procedures;
• Subjects must have a body mass index (BMI) within the range of 18 kg/m2 to 32 kg/m2(\> 45 kg), inclusive;
• Subjects must be in general good health, based upon the results of medical history, physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram (ECG), as judged by the Investigator;
• Subjects must have normal hematologic function at the Screening Visit, defined as the following:
• o Hemoglobin \>= 11.5 (female) or \>= 12.5 (male); Note: Subjects with non-clinically significant out-of-range values may be rescreened once for purposes of determining study eligibility.
• Subjects must have all safety laboratory parameters (serum chemistry, hematology, and urinalysis) within normal limits (laboratory reference range) at the Screening and Check-in (Day -1) Visit or, if outside of the normal limits, must meet both of the following criteria:
• Considered by the Investigator to not be clinically significant; and
• Abnormal liver function test results (alanine aminotransferase, aspartate aminotransferase, or total bilirubin level) must be \< 1.5 × upper limit of normal of the laboratory reference range.
• Note: Subjects with non-clinically significant out-of-range values may be rescreened once for purposes of determining study eligibility.
• Subjects must confirm they have previously tolerated prescription opioids;
• Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, bilateral salpingectomy, and/or bilateral oophorectomy at least 26 weeks prior to the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at the Screening Visit based on the central laboratory's ranges;
• Female subjects of childbearing potential must not be pregnant, lactating, or planning a pregnancy from the Screening Visit to 30 days after administration of the last dose of study drug and must have a negative serum pregnancy test result at the Screening Visit and a negative urine pregnancy test result at Day -1 of each treatment period;
• Female subjects of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) with male partners must agree to use a medically accepted contraceptive regimen during their participation in the study and for 30 days after the last administration of study drug. All male subjects with female partners of childbearing potential must agree to use a medically accepted contraceptive regimen during their participation in the study and for 90 days after the last administration of study drug. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy;
• For male subjects enrolled in the study:

You may not qualify if:

• Subjects with a history or presence of significant cardiovascular, hepatic, renal, hematologic, gastrointestinal, infectious, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease, or have any other condition that in the opinion of the Investigator, could potentially impact the safety of the subject or metabolism of the study drug;
• Subjects with a clinically significant history or presence of any gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), liver or kidney disease, gastric bypass, gastric stapling, use of Lapband, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug;
• Subjects who are positive for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), or hepatitis C virus antibody (HCVAb) at the Screening Visit;
• Subjects who have a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within 2 years prior to the Screening Visit or are unwilling to agree to abstain from alcohol and drugs throughout the study;
• Subjects with positive screen results for drugs of abuse, alcohol, or cotinine at Screening or Check-in (Day -1) Visit;
• Subjects who have lost or donated \> 480 mL of whole blood or blood products within 60 days prior to the Screening Visit;
• Subjects who have used any prescription or over-the-counter medication or vitamins/herbal supplements (with the exception of hormonal contraceptives and sporadic use of acetaminophen or ibuprofen) within 7 days or 5 half-lives (whichever is longer) prior to randomization until completion of the End of Study Visit, and that in the Investigator's opinion may impact subject safety or the validity of the study results; Note: Within 14 days if the drug is known or suspected to effect hepatic or renal clearance capacity or if the drug is known to be a potential moderate or strong inhibitor/inducer of cytochrome P450 enzymes (e.g., barbiturates, phenothiazine, cimetidine, carbamazepine, etc).18 Vaccinations, including the Coronavirus Disease of 2019 (COVID-19) vaccine, are allowed as long as the vaccines are administered at least 72 hours prior to Check-in (Day -1) Visit.
• Subjects who have used medications that affect gastrointestinal motility, gastric emptying, or gastric pH (potential hydrogen), such as metoclopramide, proton pump inhibitors, and/or H2 blockers, within 14 days prior to randomization until completion of the End of Study Visit;
• Subjects who have used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, electronic cigarettes, chewing tobacco, nicotine patch, or nicotine gum) within 28 days prior to Check-in (Day -1) Visit;
• Subjects who have a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Check-in (Day -1) Visit;
• Subjects who have clinically relevant abnormal physical findings, ECG, or laboratory values at or during the Screening Visit that, in the opinion of the Investigator, could interfere with the objectives of the study or the safety of the subjects;
• Subjects with a known hypersensitivity to any component in the formulations of hydrocodone or other opioids;
• Subjects with any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subjects' participation in the study;
• Subjects must not consume beverages and foods containing alcohol, poppy seeds, or caffeine/xanthine, or energy drinks from 24 hours prior to Check-in (Day -1) Visit until after the last sample collection of each treatment period;
• Subjects must not consume products containing grapefruit from 48 hours prior to Check-in (Day -1) Visit until after the last sample collection of each treatment period;

Sponsors & Collaborators

• Elysium Therapeutics, Inc.: lead
• Medpace, Inc.: collaborator
• Charles River Laboratories International Inc.: collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• Ohio Third Frontier: collaborator

Study Sites (1)

Medpace

Cincinnati, Ohio, 45227, United States

RECRUITING

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Leela Vrishabhendra, MD

  Medpace, Inc.

  PRINCIPAL INVESTIGATOR

• Lynn Webster, MD

  Elysium Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Brady Hamel, MS

CONTACT

866.872.2349; B.Hamel@Medpace.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 7, 2022
• Study Start: September 27, 2022
• Primary Completion: March 20, 2024
• Study Completion: March 31, 2024
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)