Study to Investigate the Safety, Tolerability and Pharmacokinetics of QEV-817 Oral Suspension

NCT06585163 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: QEV-817-1015R44DA055336
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This study has been designed to assess the safety, tolerability, and pharmacokinetics of a therapeutic dose of hydrocodone bitartrate with and without an oral dose of doxapram hydrochloride in healthy volunteers who are naltrexone-blocked.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

  Incidence, nature, and severity of TEAEs

  Day 1 to Day 5

• Number of Participants with Abnormal Laboratory Assessments, 12-Lead Electrocardiogram (ECG), and Vital Signs

  Changes from baseline in physical examination, vital signs, 12-lead ECG assessment and pulse oximetry

  Day 1 to Day 5

Secondary Outcomes (3)

• Plasma PK Parameters (Cmax)

  Day 2 and Day 4

• Plasma PK Parameters (AUC0-inf)

  Day 2 and Day 4

• Plasma PK Parameters (Tmax)

  Day 2 and Day 4

Study Arms (2)

Sequence A - Hydrocodone alone followed by combined (hydrocodone + doxapram)

EXPERIMENTAL

Subjects randomized to Sequence A will first receive a single oral administration of hydrocodone bitartrate alone on Study Day-2 and then receive a combination of hydrocodone bitartrate and doxapram hydrocholoride on study Day-4 (after a 48 hour wash-out).

Drug: Hydrocodone Bitartrate; Drug: Doxapram Hydrochloride

Sequence B - Combined (hydrocodone + doxapram) followed by hydrocodone alone

EXPERIMENTAL

Subjects randomized to Sequence B will first receive a single combined administration of hydrocodone bitartrate and doxapram hydrocholoride on Study Day-2 and then receive hydrocodone alone on study Day-4 (after a 48 hour wash-out).

Drug: Hydrocodone Bitartrate; Drug: Doxapram Hydrochloride

Interventions

Hydrocodone Bitartrate DRUG

Hydrocodone bitartrate oral suspension

Also known as: NDC 51634-0014

Sequence A - Hydrocodone alone followed by combined (hydrocodone + doxapram); Sequence B - Combined (hydrocodone + doxapram) followed by hydrocodone alone

Doxapram Hydrochloride DRUG

Doxapram hydrocholoride oral suspension

Also known as: NDC 10920-601

Sequence A - Hydrocodone alone followed by combined (hydrocodone + doxapram); Sequence B - Combined (hydrocodone + doxapram) followed by hydrocodone alone

Eligibility Criteria

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

You may qualify if:

• Male or female aged 18-55 years, inclusive, on the day of screening.
• Willing to abstain from alcohol and strenuous physical activity (i.e., strenuous, or unaccustomed weightlifting, running, bicycling, etc.) from 48 hours prior to study treatment administration until discharge from the clinical unit and prior to each outpatient visit.
• Have normal laboratory values, as defined per protocol, at screening.
• Absence of cardiac arrythmias, as well as corrected QT interval (QTc) \< 450 ms in males and QTc \< 460 ms in females based on 12-lead ECG findings at screening.
• Body weight ≥50 kg and body mass index (BMI) within the range of 19-32 kg/m2 (inclusive).
• Has never used opioids for non-therapeutic purposes (i.e., for recreational effects). Subjects with a history of valid medical use under prescription must have not used an opioid for at least three (3) months prior to Day 1.
• Women of childbearing potential (WOCBP), as defined in Section 10.4, must have a negative serum pregnancy test within one (1) week AND a negative urine pregnancy test on Day 2, prior to the start of study treatment; Must not be breastfeeding, lactating, or planning a pregnancy during the study and for at least 32 days (5 half-lives plus 30-days) after the last dose of study intervention
• Postmenopausal females must have a documented serum follicle-stimulating hormone (FSH) level \>40 mIU/mL (milli international units per milliliter) at screening to confirm menopause.
• Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 92 days (5 half-lives + 90-day spermatogenesis cycle) after the last dose of study intervention; must not donate sperm for at least 92 days (5 half-lives + 90-day spermatogenesis cycle) after the last dose of study intervention.

You may not qualify if:

• Female subject who is pregnant or lactating.
• Have any vital sign abnormalities as described in the protocol.
• Recreational opioid user who has used opioids for non-therapeutic purposes (i.e., for psychoactive effects) or who is physically dependent on any illicit or prescription opioid, and/or currently participating in a treatment program for individuals with opioid dependence.
• Known allergy or history of significant adverse reaction to hydrocodone or its metabolites, other opioids, or related compounds, doxapram hydrochloride, naltrexone, naloxone, or to any of the excipients in QEV-817.
• History of or currently has hypoventilation syndrome or sleep apnea and is on non-invasive ventilation (e.g., CPAP).
• Clinically meaningful infection/injury/illness within one month prior to screening.
• Active malignancy (excluding squamous or basal cell carcinoma of the skin) within 5 years of screening.
• Subjects with hepatic impairment as defined by screening alanine transaminase (ALT), aspartate transaminase (AST) or total bilirubin \>3× upper limit of normal (ULN).
• Subjects with renal impairment as defined by screening estimated creatinine clearance/eGFR (estimated glomerular filtration rate) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is \<60 mL/min/1.73 m2.
• Donation of blood (\>450 mL) or significant blood loss within 56 days.
• Current (or recent history of) psychiatric illness or mental impairment.
• Clinically meaningful current (or history of) unstable chronic disease; medical abnormality; or significant cardiovascular (including significant cardiovascular impairment, uncompensated heart failure, severe coronary artery disease, severe hypertension), endocrine, gastrointestinal, neurological disorder (including cognitive disorders); or metabolic disease.
• Currently active (or history of) epilepsy, seizure disorder, serious head injury, cerebral vascular accident, or cerebral edema.
• Current treatment with monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, sympathomimetic drugs, neuromuscular blocking agents, narcotics, antihistamines, antipsychotics, antianxiety agents, or other central nervous system (CNS) depressants.
• Use of any prescription or over the counter (OTC) medications including food supplements and herbal medications (e.g., St. John's wort), with the exception of contraceptive medications or a daily multivitamin, within fourteen (14) days prior to study treatment administration. Use of CYP3A4 inhibitors or inducers is prohibited within 28 days prior to the first treatment and throughout the treatment and follow-up periods.

Sponsors & Collaborators

• Quivive Pharma, Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Interventions

Hydrocodone; Doxapram

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Ryu Komatsu, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huan Hsu, MD

CONTACT

216-444-2200; HSUH@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized to receive A) hydrocodone and B) hydrocodone + doxapram in one of two possible sequences (ie. A followed by B or B followed by A).

Study Record Dates

• First Submitted: September 1, 2024
• First Posted: September 5, 2024
• Study Start: September 1, 2024
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: September 5, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Anyone who wishes to access the data for any purpose.

Locations

US (1)