Opioid Use Disorder, ModeratePhase 1NCT05251376

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

A Phase 1 study testing Levomethadone HCl, Methadone and Morphine Sulfate in people with Opioid Use Disorder, Moderate, run by Lyndra Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 18 to 59 years
Conditions the study is for: Opioid Use Disorder, Moderate
What is being tested?: Levomethadone HCl, Methadone and Morphine Sulfate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 28 Feb 2022to 19 Dec 2022
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 59 years
All sexes
No healthy volunteers
Adult

Who may be able to join

To be eligible to participate in the study, individuals must meet all the following inclusion criteria at Screening (and at other timepoints, where specified):
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).

Who cannot join

To be eligible to participate in the study, individuals must not meet any of the following exclusion criteria at Screening (and at other timepoints, where specified):
1. Known clinically significant esophageal or GI disease, including but not limited to:
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.
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.

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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
Suicidal ideation associated with actual intent and a method or plan in the past 6 months, as measured by the C-SSRS (i.e., "Yes" answers on items 4 or 5) at Screening or Day 1, or has a history of suicide attempt within the last 2 years
Chronic pain that requires chronic opioid treatment
Active SARS-CoV-2 infection, as defined in the site-specific COVID 19 Risk Mitigation Plan
History of pernicious anemia
History of advanced cirrhosis
Use of the below in the 2 weeks before enrollment:
Proton pump inhibitors and H2 blockers
Prokinetics
Grapefruit juice, blood oranges, Seville (bitter) oranges, and star fruit
Medications that may interfere with the absorption, metabolism, or excretion of methadone (see Appendix 18.1)
Medications that have a known risk of Torsades des Pointes (see Appendix 18.2)
Concomitant medications, natural remedies, supplements, or vitamins that are associated with changes to gastric motility or pH. Use of antacids is permissible, except for within 2 hours of dosing with LYN 014
Benzodiazepines except for treatment of insomnia (short/medium acting benzodiazepines used occasionally (1 or 2 times per week)
Hormonal contraceptives
Use of blood products within 3 months of Screening.
Medical history or current diagnosis of chronic obstructive pulmonary disorder, restrictive lung disease, asthma, or any condition that could contribute to respiratory distress during study participation.
Clinically significant abnormal safety (e.g., physical examination, vital signs) or safety laboratory assessments at Screening, specifically:
Presence of a clinically significant abnormal laboratory result on blood or urine safety tests
Anemia (hemoglobin below lower limit of normal reference range and considered to be clinically significant)
Alanine aminotransferase or aspartate aminotransferase ≥3.0 × upper limit of normal or total bilirubin ≥1.5 × upper limit of normal
Moderate or severe renal insufficiency (Glomerular Filtration Rate <60 mL/min as determined using the Cockcroft Gault formula)
Heart rate <60 beats per minute (bpm)
Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg
Glycated hemoglobin (hemoglobin A1c; HbA1c) ≥6.5 mmol/L
Thrombocytopenia (platelets <150 × 109/L) or bleeding diathesis (International Normalization Ratio > 1.4)
Positive fecal occult blood test (FOBT) at Screening
The following specified patterns of substance use:
Concomitant substance use disorder other than OUD, caffeine use disorder, or nicotine use disorder
Positive urine drug screen for cocaine, amphetamine, methamphetamine, barbiturates, propoxyphene, phencyclidine, or buprenorphine
Cannabis use disorder
Positive ethanol breathalyzer result
Women of childbearing potential and men, who are unwilling to use acceptable means of contraception through the EOS. For clarity, women who are at least 1 year post menopausal are considered not of childbearing potential and can be included in the study. Acceptable means of contraception include:
Individuals who have been surgically sterilized
Females of childbearing potential: diaphragm, contraceptive sponge, or intrauterine device in use before enrollment, in combination with use of a condom for their male partners
Males: condom in combination with any of the above means of contraception for their female partners
All individuals: abstinence is only acceptable if a subject chooses not to be sexually active
Individuals who are nursing or have a positive or indeterminate pregnancy test at Screening (serum test) or Day 1 (urine test).
Use of any experimental agent within 3 months or 5 half lives of Screening, whichever is longer.
Employees or immediate family members of employees of the site, Sponsor, or study related vendors.
History of a serious allergic or hypersensitivity reaction to LYN 014 components or any components of morphine sulfate or ancillary medications.
History of X ray, computed tomography scan or angiogram of the abdomen within 1 year of Screening.

About this study

Official title: 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

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

Read the detailed description

Lyndra Therapeutics is currently developing extended release (ER) capsules for weekly administration across therapeutic areas with certain medications for which consistent pharmacokinetics (PK) or enhanced adherence may translate to improved efficacy, and possibly better safety. LYN-014 ER capsules are intended to provide comparable levomethadone exposure to daily treatment with racemic methadone for people with opioid use disorder (OUD). Compared to daily methadone dosing, LYN-014 could provide greater accessibility to methadone therapy and reduce the time devoted to obtaining medication the number of visits to methadone clinics, and thus reduce the stigma associated with methadone treatment, improve the quality of life for patients, and reduce the potential for diversion. This single dose study will evaluate the safety, tolerability, and PK of LYN-014 in individuals with OUD who are stable on daily methadone treatment. Data from this study will inform formulation optimization and dose selection for further development.

Conditions: Opioid Use Disorder, Moderate
Being tested: Levomethadone HCl, Methadone, Morphine Sulfate, x-ray, blood tests
Medical subject headings: Opioid-Related Disorders, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Levomethadone HClDrug
Also called extended-release levomethadone
One dose given orally on Day 8 of the study.
MethadoneDrug
Also called oral methadone
Daily usual oral dose given on Day 1 and Day 2 of the study.
Morphine SulfateDrug
Also called morphine
Administered daily and as needed from Day 3 of the study until subject back on usual daily methadone dose.
x-rayDiagnostic test
Also called abdominal x-ray
Abdominal x-rays done at specific study timepoints to assess the location of the LYN-014.
blood testsDiagnostic test
Also called Blood draws, lab tests
Done at specific timepoints throughout the study for PK (pharmacokinetics), genotyping and safety labs.

Study groups in NCT05251376
Study group	Role	What they receive
LYN-014 Extended-Release Levomethadone HCl	Experimental	Extended-release levomethadone HCl 187 mg administered orally once on Day 8 of the study. Receives: Drug: Levomethadone HCl; Drug: Methadone; Drug: Morphine Sulfate; Diagnostic Test: x-ray; Diagnostic Test: blood tests

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 52 days

Secondary outcomes (22)

To characterize the PK of methadone enantiomers after methadone dosing (Cmin)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Cmin (Minimum Concentration)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Tmin)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Tmin (Time at minimum concentration)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Cmax)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Cmax (Maximum concentration)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Tmax)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Tmax (Time at maximum concentration)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Kel)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Kel (Elimination Rate Constant)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (AUC0-24)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate AUC0-24 (Area under the curve from 0 to 24 hours)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (AUC0-t)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate AUC0-t (Area under the curve from 0 to t hours)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (AUC0-∞)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate AUC0-∞ (Area under the curve from 0 to infinity)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Clast)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Clast (Last measurable concentration)
Measured: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Tlast)
PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Tlast (Time at last measurable concentration)
Measured: 52 days
To characterize the PK of LYN 014 compared with that of daily methadone Cmax Extended Release to Cmax Immediate Release
Compare the PK ratio of Cmax (maximum concentration) ER (LYN-014) to Cmax (maximum concentration) IR (methadone).
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Cmin)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Cmin (minimum concentration)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Tmin)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Tmin (Time at minimum concentration)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Cmax)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Cmax (Maximum concentration)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Tmax)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Tmax (Time at maximum concentration)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Kel)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Kel (elimination rate constant)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-24)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-24 (Area under the curve from 0 to 24 hours)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-t)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-t (Area under the curve from 0 to t hours)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-∞)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-∞ (Area under the curve from 0 to infinity)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Clast)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Clast (last measurable concentration)
Measured: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Tlast)
PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Tlast (Time at last measurable concentration)
Measured: 52 days
To assess gastrointestinal (GI) transit and exit properties of LYN 014.
GI transit and exit properties of LYN 014 assessed by X ray imaging and fecal recovery.
Measured: 52 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Feb 202219 Dec 2022

First posted22 Feb 2022
Study start28 Feb 2022
Primary completion19 Dec 2022
Study completion19 Dec 2022

Why it stopped: Sponsor decision.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Opioid Use Disorder, ModerateStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05251376
Sponsor's protocol ID: LYN-014-C-101
Other IDs: 4UH3DA050310-02
Status last verified: Jan 2023
First submitted: 20 Jan 2022
Last updated: 19 Jan 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Enrolling by invitation
TRTME: Improving Outpatient Initiation of Medication for Opioid Use Disorder Following Hospitalization
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RecruitingPhase 2
Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the Treatment of Opioid Use Disorder
Opioid Use Disorder, Opioid Use Disorder, Moderate
Not yet recruiting
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Opioid Use Disorder, Opioid Use Disorder, Moderate

All Opioid Use Disorder, Moderate trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT05251376
Acronym / sponsor ID: LYN-014-C-101
Conditions: Opioid Use Disorder, Moderate
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Sponsor decision.
Enrolment: 0 participants (actual)
Lead sponsor: Lyndra Inc.Industry (pharma, biotech, devices)
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 28 Feb 2022 (actual)
Primary completion: 19 Dec 2022 (actual)
Study completion: 19 Dec 2022 (actual)
First posted: 22 Feb 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
LYN-014 Extended-Release Levomethadone HCl	Experimental	Drug: Levomethadone HCl, Drug: Methadone, Drug: Morphine Sulfate, Diagnostic Test: x-ray, Diagnostic Test: blood testsExtended-release levomethadone HCl 187 mg administered orally once on Day 8 of the study.

Who may qualify

Ages: 18 to 59 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (5 listed)

To be eligible to participate in the study, individuals must meet all the following inclusion criteria at Screening (and at other timepoints, where specified):
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).

Key exclusion criteria (57 listed)

To be eligible to participate in the study, individuals must not meet any of the following exclusion criteria at Screening (and at other timepoints, where specified):
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.
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Levomethadone HClAlso: extended-release levomethadoneOne dose given orally on Day 8 of the study.	Drug	LYN-014 Extended-Release Levomethadone HCl
MethadoneAlso: oral methadoneDaily usual oral dose given on Day 1 and Day 2 of the study.	Drug	LYN-014 Extended-Release Levomethadone HCl
Morphine SulfateAlso: morphineAdministered daily and as needed from Day 3 of the study until subject back on usual daily methadone dose.	Drug	LYN-014 Extended-Release Levomethadone HCl
x-rayAlso: abdominal x-rayAbdominal x-rays done at specific study timepoints to assess the location of the LYN-014.	Diagnostic test	LYN-014 Extended-Release Levomethadone HCl
blood testsAlso: Blood draws, lab testsDone at specific timepoints throughout the study for PK (pharmacokinetics), genotyping and safety labs.	Diagnostic test	LYN-014 Extended-Release Levomethadone HCl

Primary outcome

To evaluate the safety and tolerability of the LYN-014 dose when administered orally as a single dose
Time frame: 52 days
Incidence of treatment-emergent adverse events and serious adverse events
To characterize the PK of levomethadone for LYN-014 (Cmin)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Cmin (minimum concentration)
To characterize the PK of levomethadone for LYN-014 (Tmin)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Tmin (Time at minimum concentration)
To characterize the PK of levomethadone for LYN-014 (Cmax)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Cmax (maximum concentration)
To characterize the PK of levomethadone for LYN-014 (Tmax)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Tmax (Time at maximum concentration)
To characterize the PK of levomethadone for LYN-014 (Kel)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate Kel (Elimination Rate Constant)
To characterize the PK of levomethadone for LYN-014 (AUC0-20)
Time frame: 52 days
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)
To characterize the PK of levomethadone for LYN-014 (AUC0-t)
Time frame: 52 days
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)
To characterize the PK of levomethadone for LYN-014 (AUC0-∞t)
Time frame: 52 days
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)
To characterize the PK of levomethadone for LYN-014 (C last)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate C last (Last measurable concentration)
To characterize the PK of levomethadone for LYN-014 (T last)
Time frame: 52 days
PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate T last (Time at last measurable concentration)

22 secondary outcomes

To characterize the PK of methadone enantiomers after methadone dosing (Cmin)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Tmin)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Cmax)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Tmax)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Kel)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (AUC0-24)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (AUC0-t)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (AUC0-∞)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Clast)
Time frame: 52 days
To characterize the PK of methadone enantiomers after methadone dosing (Tlast)
Time frame: 52 days
To characterize the PK of LYN 014 compared with that of daily methadone Cmax Extended Release to Cmax Immediate Release
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Cmin)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Tmin)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Cmax)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Tmax)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Kel)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-24)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-t)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-∞)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Clast)
Time frame: 52 days
To evaluate possible conversion of Levomethadone to Dextromethadone (Tlast)
Time frame: 52 days
To assess gastrointestinal (GI) transit and exit properties of LYN 014.
Time frame: 52 days

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2023.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Richard Scranton, MD, MPH principal investigator

Lyndra Therapeutics INC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Levomethadone HCl, Methadone and Morphine Sulfate in people with Opioid Use Disorder, Moderate, run by Lyndra Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 57 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 19 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the safety and tolerability of the LYN-014 dose when administered orally as a single dose (time frame: 52 days). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05251376.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2023.