Opioid Use Disorder
Conditions
Brief summary
The purpose of this study is to evaluate the safety and blood levels of a medicine, naltrexone, contained within an implant in healthy volunteers age 18 to 65 years. To do this, the implant containing the drug will be inserted under the skin, left in place for 3 months and then removed.
Detailed description
Naltrexone (NTX) is a medication that helps people with opioid and alcohol dependence. It works by blocking the effects of opioids like heroin in the body. In the United States, participants can get NTX in two forms: a pill participants take once a day (Revia) and a shot participants get once a month (Vivitrol). Even though NTX is good at stopping the effects of opioids, some people find it hard to take it regularly. That's why scientists are looking into making a new version of NTX that participants only need to take once a month. This could make it easier for people with opioid use problems to stick with their treatment plan. The device being tried out in this research is called BIOPIN-6. It's made to stay in the body for more than a month. The study will go on for three months and aims to check if the BIOPIN-6 is safe and how much medicine it releases into the blood. Once the three months are up, the device will be taken out.
Interventions
COMBINATION_PRODUCTBIOPIN-6 Active Implant with Naltrexone
An extended release formulation of naltrexone implanted in the subcutaneous space.
DEVICEBIOPIN-6 Placebo Implant
The placebo will be an implant consisting of the poly-d-l Lactic Acid and polycaprolactone contained in BIOPIN 6 without naltrexone.
Sponsors
Akyso Therapeutics, LLC
National Institute on Drug Abuse (NIDA)
Laboratory Corporation of America
Cognitive Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The surgeon and the team performing the subcutaneous implant and removal will be unmasked. All other staff and subjects will be masked.
Intervention model description
Determine naltrexone and 6b-naltrexole pharmacokinetic parameters in subjects administered a single dose of BIOPIN 6 \[BIOPIN 6 implants containing 4.8g (dose-level #1) or 9.6g (dose-level #2) naltrexone\]. Each of the two dose groups will be compared to a placebo implant group. The initial study design had 3 groups and a high dose group receiving 14.4 g naltrexone. After the PK data became available for the second cohort, the sponsor chose to not proceed with the final cohort because the target PK parameters had been achieved with the 9.6 gram group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all of the following criteria to be included in the study: * Healthy male or female volunteer, aged 18-to-55 years, inclusive. * BMI must be between 18 and 32 kg/m2 (inclusive) and weigh a minimum of 50 kg (110 lbs). * If female, be postmenopausal (at least 2 years prior to dosing) or agree to use an acceptable form of birth control from screening until 12 weeks after dosing. Subjects who claim postmenopausal status will have status confirmed with a follicle stimulating hormone (FSH) test. Acceptable forms of birth control for females include the following: * Vasectomized partner (at least 6 months prior to dosing) * Surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) at least 6 months prior to dosing * Non-surgical permanent sterilization (eg, Essure procedure) at least 3 months prior to dosing. * Abstinence (must agree to use a double barrier method if they become sexually active during the study) * Double barrier (diaphragm with spermicide; condoms with spermicide) * Oral hormonal contraceptives * Not Breast feeding * Negative tests for human immunodeficiency virus (HIV), Hepatitis C antibody, Hepatitis B surface antigen, and Covid * Able and willing to comply with the requirements of the protocol * Able and willing to provide written informed consent * Willing to undergo a minor surgical procedure under local anesthetic to allow for investigational drug administration in the subcutaneous tissue * Agree to avoid blunt trauma to the implantation site * Agree that after implantation, not to shower for 2 days and not to bathe/swim for 4 weeks
Exclusion criteria
Subjects must have none of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Naltrexone Plasma Concentration Area Under the Curve (AUC₀-Day 98) | Predose and 1, 3, 6, 12, 24, 48, and 72 hours post-implant; Days 7 and 10; Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 post-implant; Week 12 pre-explant and 1, 3, 6, 12, 24, 48, 72, and 96 hours post-explant; and Week 14 (Day 98). | Area under the plasma naltrexone concentration-time curve (AUC) from implant placement through Day 98, calculated using noncompartmental pharmacokinetic methods based on serial plasma concentration measurements. Plasma concentrations below the lower limit of quantification (LLOQ) were represented as 0 in the reported results; therefore, 0 values do not represent placeholder entries. |
| Naltrexone Plasma Levels (Peak) | Predose and 1, 3, 6, 12, 24, 48, and 72 hours post-implant; Days 7 and 10; Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 post-implant; Week 12 pre-explant and 1, 3, 6, 12, 24, 48, 72, and 96 hours post-explant; and Week 14 (Day 98). | Naltrexone Peak Plasma Concentration (Cmax) \[ng/ml\]. Plasma concentrations below the lower limit of quantification (LLOQ) were represented as 0 in the reported results; therefore, 0 values do not represent placeholder entries. |
| Time to Peak Plasma Concentration of Naltrexone (Tmax) | Predose and 1, 3, 6, 12, 24, 48, and 72 hours post-implant; Days 7 and 10; Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 post-implant; Week 12 pre-explant and 1, 3, 6, 12, 24, 48, 72, and 96 hours post-explant; and Week 14 (Day 98). | Time to maximum observed plasma concentration (Tmax) of naltrexone following implant placement. |
| 6-β-naltrexol Plasma Concentration Area Under the Curve (AUC₀-98 Days) | Predose and 1, 3, 6, 12, 24, 48, and 72 hours post-implant; Days 7 and 10; Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 post-implant; Week 12 pre-explant and 1, 3, 6, 12, 24, 48, 72, and 96 hours post-explant; and Week 14 (Day 98). | Area under the plasma concentration-time curve (AUC) of 6-β-naltrexol from implant placement through Day 98. Plasma concentrations below the lower limit of quantification (LLOQ) were represented as 0 in the reported results; therefore, 0 values do not represent placeholder entries. |
| 6-β-naltrexol Peak Plasma Concentration (Cmax) | Predose and 1, 3, 6, 12, 24, 48, and 72 hours post-implant; Days 7 and 10; Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 post-implant; Week 12 pre-explant and 1, 3, 6, 12, 24, 48, 72, and 96 hours post-explant; and Week 14 (Day 98). | Maximum observed plasma concentration (Cmax) of 6-β-naltrexol following implant placement.\[ng/ml\]. Plasma concentrations below the lower limit of quantification (LLOQ) were represented as 0 in the reported results; therefore, 0 values do not represent placeholder entries. |
| Time to Peak Plasma Concentration of 6-β-naltrexol (Tmax) | Day 0 to Day 98 | Time to maximum observed plasma concentration (Tmax) of 6-β-naltrexol following implant placement. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTodd Bertoch, MD
Cenexel JBR
Participant flow
Recruitment details
Healthy adult volunteers were recruited at a single U.S. clinical research site (JBR Clinical Research, Salt Lake City, UT) between June 2024 and January 2025.
Pre-assignment details
Participants provided informed consent and underwent screening including medical history, physical exam, laboratory testing, ECG, urine drug screen, infectious disease testing, pregnancy testing (if applicable), and naloxone challenge to confirm absence of opioid dependence. Eligible subjects were randomized to receive BIOPIN 6 implant (4.8 g or 9.6 g) or placebo implant.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 30 Years STANDARD_DEVIATION 2.5 |
| BMI | 26.78 kg/m² STANDARD_DEVIATION 3.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 5 / 6 | 6 / 6 | 2 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
None listed