ENA-001 for Opioid Induced Respiratory Depression

NCT06967259 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: ENA-001-1094R44DA057133-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a Phase I clinical trial to assess the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles with single intravenous (IV) and intramuscular (IM) doses of ENA-001.

Conditions

Respiratory Depression

Outcome Measures

Primary Outcomes (6)

• Range values of laboratory tests (Safety)

  To determine the safety of single-dose safety of ENA-001 compared to placebo in healthy volunteers after Intravenous (IV) and Intramuscular (IM) injection. Primary endpoints include the laboratory range values of safety laboratory tests (hematology, coagulation, clinical chemistry, and urinalysis). Any measurement out of range will be assessed for adverse event.

  From screening to follow up visit (approx. 8 weeks)

• Range values of special chemistry tests (Safety)

  To determine the safety of single-dose safety of ENA-001 compared to placebo in healthy volunteers after Intravenous (IV) and Intramuscular (IM) injection. Primary endpoints include special chemistry assessments (Ca+2 and HCO3- or venous CO2). Any measurement out of range will be assessed for adverse event.

  From screening to follow up visit (approx. 8 weeks)

• Vital Sign measurements (Safety and tolerability)

  To determine the single-dose safety and tolerability of ENA-001 compared to placebo in healthy volunteers after Intravenous (IV) and Intramuscular (IM) injection. Primary endpoints include vital sign measurements (blood pressure and heart rate). Any measurement out of range may indicate an adverse event, meet stopping criteria, and/or indicate intolerability of ENA-001. Systolic and diastolic blood pressure (mmHg), pulse rate (HR), body temperature (°C) will be graded according to the FDA guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.

  From screening to follow up visit (approx. 8 weeks)

• Measurement of ECG parameters (Safety and tolerability)

  To determine the safety and tolerability of single-dose safety of ENA-001 compared to placebo in healthy volunteers after Intravenous (IV) and Intramuscular (IM) injection. Primary endpoints include ECG measurement. Any measurement out of range may indicate an adverse event and/or indicate intolerability of ENA-001.

  From screening to follow up visit (approx. 8 weeks)

• Complete Physical Exam Findings (Safety and tolerability)

  To determine the safety and tolerability of single-dose safety of ENA-001 compared to placebo in healthy volunteers after Intravenous (IV) and Intramuscular (IM) injection. Primary endpoints include physical examination findings. Complete physical examination will include: head, eyes, ears, nose, throat, neck, heart, chest, lungs, abdomen, extremities, skin, and neurological exam. Any post-baseline findings of the physical examination will be assessed for adverse event.

  From screening to follow up visit (approx. 8 weeks)

• Incidence of Adverse Events (Safety and tolerability)

  To determine the safety and tolerability of single-dose safety of ENA-001 compared to placebo in healthy volunteers after Intravenous (IV) and Intramuscular (IM) injection. Number of participant with adverse events and grade of AEs will be used to inform on safety and tolerability of ENA-001.

  From screening to follow up visit (approx. 8 weeks)

Secondary Outcomes (7)

• Evaluation of spirometry values (PD)

  Each dosing day (Day 1) - Approximately 3 weeks

• Evaluation of capnography values (PD)

  Each dosing day (Day 1) - Approximately 3 weeks

• Evaluation of Pulse Oximetry (PD)

  Each dosing day (Day 1) - Approximately 3 weeks

• Evaluation of ABG measurements (PD)

  Each dosing day (Day 1) - Approximately 3 weeks

• Evaluation of Cmax (Maximum observed plasma concentration) value (PK)

  Each dosing day (Day 1) - Approximately 3 weeks

Study Arms (2)

ENA-001 Treatment Arm

EXPERIMENTAL

ENA-001 for intravenous injection will be given over 3-5 seconds and will be administered via a suitable arm vein with an indwelling catheter. ENA-001 for intramuscular injection will be administered over 3-5 seconds via both deltoid muscles.

Drug: ENA-001

Placebo Treatment Arm

PLACEBO COMPARATOR

Placebo for intravenous injection will be given over 3-5 seconds and will be administered via a suitable arm vein with an indwelling catheter. Placebo for intramuscular injection will be administered over 3-5 seconds via both deltoid muscles.

Drug: Placebo Comparator

Interventions

ENA-001 DRUG

Concentration for ENA-001 IV formulation is 10 mg/mL. Concentration for ENA 001 IM formulation is 30 mg/mL.

ENA-001 Treatment Arm

Placebo Comparator DRUG

Placebo comes in 5 mL/vial. Placebo matches ENA-001 injection; however, no ENA-001 is included.

Placebo Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Subjects must be willing to give written informed consent for the trial and able to adhere to dose and visit schedules.
• Male and female, \>18 to ≤55 years of age.
• Subject must weigh ≥50 to ≤100 kg.
• Subjects must have Body Mass Index \[weight/height2 (kg/m2)\] between 18 to 30 kg/m2 (inclusive).
• Have no clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator with normal cardiac intervals appropriate for their gender. The Screening 12 lead electrocardiogram (ECG) conduction intervals must be within gender specific normal range (e.g., QTcf female \< 450 msec QT corrected for heart rate by Fridericia's cube root formula (QTcF) males \< 430 msec, PR interval ≤ 220 msec). ECGs are to be judged by the investigator or sub-investigator as per standardized procedures.
• Subjects' clinical laboratory tests (blood hematology, blood chemistry, coagulation and urinalysis and liver enzymes must be in normal range. Where applicable, normal range is defined as in the FDA guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials.
• Vital sign measurements must be within the following ranges during screening and on Day -1:
• body temperature, \>35.5 C to ≤37.5 C
• systolic blood pressure, \>90 to ≤140 mmHg
• diastolic blood pressure, \>40 to ≤95 mmHg
• pulse rate, \>55 to ≤100 bpm
• Non-vasectomized men must agree to use a condom with spermicide (when marketed in the country), double-barrier contraception, abstain from heterosexual intercourse, or have a sole sexual partner of non-childbearing potential during the trial and for 3 months after stopping the medication. Male subjects must agree not to donate sperm from the time of dosing until 90 days after dosing.
• Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative pregnancy test prior to enrollment as well as prior to each subsequent period of dosing administration, and must agree to at least one of the following contraception requirements from screening through at least 3 months after the last dose of study drug:
• Be sexually inactive (abstinent)
• Hormonal or non-hormonal intrauterine device in place for at least 3 months prior to dosing with a barrier method (condom or diaphragm) and spermicide at least 3 months after last dose of study drug.

You may not qualify if:

• Current diagnosis of psychiatric disease requiring daily medication, including controlled or uncontrolled schizophrenia and current or recently treated depressive disorders.
• Current diagnosis of Generalized Anxiety Disorder (DSM-5) requiring treatment.
• History of alcohol abuse (more than an average of two (2) drinks per day) within the past two (2) years.
• History of drug abuse within the past two years.
• Failure to take or test positive of the drug of abuse tests or alcohol urine test at screening or check-in.
• Positive for HIV, or Hepatitis B or C at screening.
• Blood donation or blood loss within 60 days of screening or plasma donation within 7 days of screening.
• Subjects with a history of bleeding disorders or coagulopathies.
• History of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary disease, sleep apnea or any other ventilatory / lung disease.
• Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening.
• History of moderate to severe motion sickness.
• Subjects who are unwilling to remove excessive facial hair preventing sealing of the occlusive face mask.
• Subjects who, in the opinion of the investigator, will not be able to participate optimally in the study.
• Any surgical or medical condition which might significantly alter the distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following, and be discussed with the Sponsor prior to enrollment into the trial:
• history of pancreatic injury or pancreatitis;

Sponsors & Collaborators

• Enalare Therapeutics Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

Dr. Vince Clinical Research

Overland Park, Kansas, 66212, United States

Location

Clinilabs

Eatontown, New Jersey, 07724, United States

Location

MeSH Terms

Conditions

Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be double-blind for treatment but not dose level. The research pharmacist at the study center will not be blinded to treatment.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study protocol is an 8-period ascending, repeated, single dose, safety and tolerability study comparing the effects of ENA-001 with placebo in 4 panels of screened healthy volunteers after single doses. The study periods will be conducted for IV (4-periods) and for IM dosing (4-periods). The study will be randomized, double-blinded, and placebo-controlled.

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: May 13, 2025
• Study Start: May 14, 2025
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)