Opioid Use Disorder, Moderate
Conditions
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
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.
Interventions
DRUGLevomethadone HCl
One dose given orally on Day 8 of the study.
DRUGMethadone
Daily usual oral dose given on Day 1 and Day 2 of the study.
DRUGMorphine Sulfate
Administered daily and as needed from Day 3 of the study until subject back on usual daily methadone dose.
DIAGNOSTIC_TESTx-ray
Abdominal x-rays done at specific study timepoints to assess the location of the LYN-014.
DIAGNOSTIC_TESTblood tests
Done at specific timepoints throughout the study for PK (pharmacokinetics), genotyping and safety labs.
Sponsors
National Institute on Drug Abuse (NIDA)
Lyndra Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
No
Inclusion criteria
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).
Exclusion criteria
To be eligible to participate in the study, individuals must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of the LYN-014 dose when administered orally as a single dose | 52 days | Incidence of treatment-emergent adverse events and serious adverse events |
| To characterize the PK of levomethadone for LYN-014 (Cmin) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 52 days | PK of levomethadone after oral administration of LYN-014, to include where possible and appropriate T last (Time at last measurable concentration) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate possible conversion of Levomethadone to Dextromethadone (Cmin) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Cmin (minimum concentration) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (Tmin) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Tmin (Time at minimum concentration) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (Cmax) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Cmax (Maximum concentration) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (Tmax) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Tmax (Time at maximum concentration) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (Kel) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Kel (elimination rate constant) |
| To characterize the PK of methadone enantiomers after methadone dosing (Tmax) | 52 days | 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) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-t) | 52 days | 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) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-∞) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate AUC0-∞ (Area under the curve from 0 to infinity) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (Clast) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Clast (last measurable concentration) |
| To evaluate possible conversion of Levomethadone to Dextromethadone (Tlast) | 52 days | PK of dextromethadone after oral administration of LYN-014, to include where possible and appropriate Tlast (Time at last measurable concentration) |
| To assess gastrointestinal (GI) transit and exit properties of LYN 014. | 52 days | GI transit and exit properties of LYN 014 assessed by X ray imaging and fecal recovery. |
| To evaluate possible conversion of Levomethadone to Dextromethadone (AUC0-24) | 52 days | 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) |
| To characterize the PK of methadone enantiomers after methadone dosing (Cmin) | 52 days | PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Cmin (Minimum Concentration) |
| To characterize the PK of methadone enantiomers after methadone dosing (Tmin) | 52 days | 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) |
| To characterize the PK of methadone enantiomers after methadone dosing (Cmax) | 52 days | PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Cmax (Maximum concentration) |
| To characterize the PK of methadone enantiomers after methadone dosing (Kel) | 52 days | PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Kel (Elimination Rate Constant) |
| To characterize the PK of methadone enantiomers after methadone dosing (AUC0-24) | 52 days | 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) |
| To characterize the PK of methadone enantiomers after methadone dosing (AUC0-t) | 52 days | 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) |
| To characterize the PK of methadone enantiomers after methadone dosing (AUC0-∞) | 52 days | 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) |
| To characterize the PK of methadone enantiomers after methadone dosing (Clast) | 52 days | PK of levomethadone and dextromethadone (S-enantiomer of methadone) after oral administration of methadone, to include where possible and appropriate Clast (Last measurable concentration) |
| To characterize the PK of methadone enantiomers after methadone dosing (Tlast) | 52 days | 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) |
| To characterize the PK of LYN 014 compared with that of daily methadone Cmax Extended Release to Cmax Immediate Release | 52 days | Compare the PK ratio of Cmax (maximum concentration) ER (LYN-014) to Cmax (maximum concentration) IR (methadone). |
Outcome results
None listed