Study of LYN-014 in Individuals With Opioid Use Disorder Who Are Stable on Methadone Therapy

NCT05251376 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: LYN-014-C-1014UH3DA050310-02
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Phase 1, Single Dose, Open-label, Safety, Tolerability, and Pharmacokinetic Study of LYN-014 in Individuals with Opioid Use Disorder Who are Stable on Methadone Therapy

Conditions

Opioid Use Disorder, Moderate

Outcome Measures

Primary Outcomes (11)

• To evaluate the safety and tolerability of the LYN-014 dose when administered orally as a single dose

  Incidence of treatment-emergent adverse events and serious adverse events

  52 days

• To characterize the PK of levomethadone for LYN-014 (Cmin)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Cmin (minimum concentration)

  52 days

• To characterize the PK of levomethadone for LYN-014 (Tmin)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Tmin (Time at minimum concentration)

  52 days

• To characterize the PK of levomethadone for LYN-014 (Cmax)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Cmax (maximum concentration)

  52 days

• To characterize the PK of levomethadone for LYN-014 (Tmax)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Tmax (Time at maximum concentration)

  52 days

• To characterize the PK of levomethadone for LYN-014 (Kel)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Kel (Elimination Rate Constant)

  52 days

• To characterize the PK of levomethadone for LYN-014 (AUC0-20)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-20 (Area under the curve from 0-24 hours)

  52 days

• To characterize the PK of levomethadone for LYN-014 (AUC0-t)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-t (Area under the curve from 0 to t hours)

  52 days

• To characterize the PK of levomethadone for LYN-014 (AUC0-∞t)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-∞t (Area under the curve from 0 to infinity)

  52 days

• To characterize the PK of levomethadone for LYN-014 (C last)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate C last (Last measurable concentration)

  52 days

• To characterize the PK of levomethadone for LYN-014 (T last)

  PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate T last (Time at last measurable concentration)

  52 days

Secondary Outcomes (22)

• To characterize the PK of methadone enantiomers after methadone dosing (Cmin)

  52 days

• To characterize the PK of methadone enantiomers after methadone dosing (Tmin)

  52 days

• To characterize the PK of methadone enantiomers after methadone dosing (Cmax)

  52 days

• To characterize the PK of methadone enantiomers after methadone dosing (Tmax)

  52 days

• To characterize the PK of methadone enantiomers after methadone dosing (Kel)

  52 days

Study Arms (1)

LYN-014 Extended-Release Levomethadone HCl

EXPERIMENTAL

Extended-release levomethadone HCl 187 mg administered orally once on Day 8 of the study.

Drug: Levomethadone HCl; Drug: Methadone; Drug: Morphine Sulfate; Diagnostic Test: x-ray; Diagnostic Test: blood tests

Interventions

Levomethadone HCl DRUG

One dose given orally on Day 8 of the study.

Also known as: extended-release levomethadone

LYN-014 Extended-Release Levomethadone HCl

Methadone DRUG

Daily usual oral dose given on Day 1 and Day 2 of the study.

Also known as: oral methadone

LYN-014 Extended-Release Levomethadone HCl

Morphine Sulfate DRUG

Administered daily and as needed from Day 3 of the study until subject back on usual daily methadone dose.

Also known as: morphine

LYN-014 Extended-Release Levomethadone HCl

x-ray DIAGNOSTIC_TEST

Abdominal x-rays done at specific study timepoints to assess the location of the LYN-014.

Also known as: abdominal x-ray

LYN-014 Extended-Release Levomethadone HCl

blood tests DIAGNOSTIC_TEST

Done at specific timepoints throughout the study for PK (pharmacokinetics), genotyping and safety labs.

Also known as: Blood draws, lab tests

LYN-014 Extended-Release Levomethadone HCl

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged ≥18 and ≤59 years. Body mass index of ≥18 kg/m2 and ≤33 kg/m2. Moderate or severe OUD according to the DSM-5 criteria. Clinically stable (for at least 6 months) on oral daily methadone therapy at a dose of 80 to 100 mg and have been taking the same dose for at least 3 months, and are stably engaged in a methadone program, confirmed by a methadone provider and defined as (1) demonstrates evidence of regular attendance, (2) has not had problems with missed visits, and (3) consistently demonstrates drug-negative urine samples (except for cannabis).
• Agree to provide the study site with contact information for the clinic where they get methadone and agree that a study physician can contact the clinician providing methadone to confirm appropriateness for study participation and to manage their transition into the study and from the study back to their opioid treatment program.
• Able to read and understand study procedures and provide written informed consent before the initiation of any protocol-specific procedures.
• Willing to comply with all protocol-specified procedures and availability for the duration of the study (e.g., participant is not aware of any emergent life-changes or potential family emergencies that would interfere with a 40+ day inpatient stay).

You may not qualify if:

• \. Known clinically significant esophageal or GI disease, including but not limited to:
• a. Known strictures such as esophageal web, pyloric stenosis, small intestinal stricture, or individuals with high risk of stricture, ie, Crohn's disease b. Diagnosis of a condition known to elevate or lower gastric pH, eg, achlorhydria or hypochlorhydria c. Prior small or large bowel obstructions or varices d. Prior abdominal or upper GI surgery (prior uncomplicated laparoscopic procedures are permitted) e. History of dysphagia or aspiration in the last 5 years f. History of an esophageal motility disorder or undergoing treatment for a gastric motility disorder g. Significant history of diarrhea or constipation (non-methadone related) within 3 months of Screening h. Fewer than 3 bowel movements per week, on average i. Multiple episodes of abdominal pain in the prior 3 months j. Moderate or severe dysmenorrhea or menorrhagia (with use of pain medication) in the prior 3 months.
• k. History of gastroparesis, rumination, autoimmune gastritis, H.pylori gastritis, or irritable bowel syndrome l. History compatible with acid reflux (heartburn, regurgitation, dysphagia, chest pain, water brash, globus sensation, odynophagia) m. Medical history compatible with Achlorhydria (i.e., history of autoimmune gastritis, pernicious anemia, H. plylori infection, partial gastrectomy).
• History of moderate to severe Acid Reflux Disease or a score of ≥2 on the Acid Reflux Severity Scale (ARSS), indicating moderate to severe symptoms. The ARSS scale is as follows:
• None = 0 no symptoms Mild = 1 awareness of symptom, but easily tolerated Moderate = 2 discomfort sufficient to cause interference with normal activities Severe = 3 incapacitating, with inability to perform normal activities.
• Individuals with PILL 5 swallowing questionnaire score of 5 or greater.
• Medical history or current diagnoses indicating the presence of any of the following conditions:
• Presence of an uncontrolled, unstable, or clinically significant medical condition, mental impairment, or psychiatric disease (e.g., schizophrenia, bipolar, major depression, or borderline personality disorder) that could put the subject at risk because of participation in the study, interfere with the subject's ability to participate in the study or influence the interpretation of safety or PK evaluations
• History of a major cardiovascular event (myocardial infarction, cardiac surgery or revascularization, unstable angina, stroke, or transient ischemic attack) or a hospitalization for heart failure within 6 months of Screening
• Presence of Long QT Syndrome
• Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of Screening, in the opinion of the Sponsor/designee or Principal Investigator
• Known immunocompromised status, including individuals who have undergone organ transplantation, on immunosuppression for an immune mediated disease, or are positive for HIV
• Positive test for active hepatitis B at Screening, unless hepatitis B infection has been resolved for ≥1 year
• Donated more than 250 mL of blood within 4 weeks of Screening
• Difficulties with venipuncture/cannulation, including difficulty accessing veins for blood sampling and/or history of coagulopathy or endocarditis

Sponsors & Collaborators

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

MeSH Terms

Conditions

Opioid-Related Disorders; Lymphoma, Follicular

Interventions

Methadone; Morphine; X-Rays; Radiography, Abdominal; Hematologic Tests; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; 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; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Clinical Laboratory Techniques; Investigative Techniques; Specimen Handling; Punctures; Surgical Procedures, Operative

Study Officials

• Richard Scranton, MD, MPH

  Lyndra Therapeutics INC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: February 22, 2022
• Study Start: February 28, 2022
• Primary Completion: December 19, 2022
• Study Completion: December 19, 2022
• Last Updated: January 19, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share