Study of the BIOPIN 6 Naltrexone Implant in Healthy Adults

NCT06216132 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: BIOPIN1015UG3DA048338-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (6)

• Naltrexone Plasma Concentration Area Under the Curve (AUC₀-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.

  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 Plasma Levels (Peak)

  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.

  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 Peak Plasma Concentration of Naltrexone (Tmax)

  Time to maximum observed plasma concentration (Tmax) of naltrexone following implant placement.

  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).

• 6-β-naltrexol Plasma Concentration Area Under the Curve (AUC₀-98 Days)

  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.

  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).

• 6-β-naltrexol Peak Plasma Concentration (Cmax)

  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.

  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 Peak Plasma Concentration of 6-β-naltrexol (Tmax)

  Time to maximum observed plasma concentration (Tmax) of 6-β-naltrexol following implant placement.

  Day 0 to Day 98

Study Arms (2)

BIOPIN-6 active implant

EXPERIMENTAL

Two sequential cohorts receiving 4.8 or 9.6 BIOPIN 6 implanted into a subcutaneous pocket in the upper abdominal wall.

Combination Product: BIOPIN-6 Active Implant with Naltrexone

BIOPIN-6 placebo implant

PLACEBO COMPARATOR

The placebo will be an implant consisting of the poly-d-l Lactic Acid and polycaprolactone contained in BIOPIN 6 without naltrexone.

Device: BIOPIN-6 Placebo Implant

Interventions

BIOPIN-6 Active Implant with Naltrexone COMBINATION_PRODUCT

An extended release formulation of naltrexone implanted in the subcutaneous space.

Also known as: BIOPIN, Subcutaneous naltrexone implant, Extended release naltrexone implant

BIOPIN-6 active implant

BIOPIN-6 Placebo Implant DEVICE

The placebo will be an implant consisting of the poly-d-l Lactic Acid and polycaprolactone contained in BIOPIN 6 without naltrexone.

BIOPIN-6 placebo implant

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Clinically significant abnormal finding on the physical exam, medical history, electrocardiogram (EKG), or clinical laboratory results at screening. In particular, values of liver function tests (ALT, AST, bilirubin, albumin, GGT) and kidney function tests (creatinine, blood urea nitrogen) and reticulocytes shall not deviate by more than 25% from the ranges of normal.
• Blood pressure: systolic \>140 mmHg, diastolic \>90 mmHg. \[Europe Soc Hypertension guidelines\]
• Heart rate: \>100 beats/minute.
• Hemoglobin for female \<11.5 and for male \<12.5 are excluded.
• Have a known or suspected history or family history of adverse reactions or hypersensitivity to the study drugs or to drugs with a similar chemical structure.
• History or presence of gastrointestinal, hepatic or renal disease, or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Is on anticoagulant medications other than aspirin or NSAIDs. Agree to stop aspirin or NSAIDs 1 week prior to Biopin 6 implantation
• Used any over-the-counter (OTC) medication, nutritional or dietary supplements, herbal preparations, or vitamins within 7 days prior to the first dose of medication.
• Used any prescription medication within 14 days prior to the first dose of study medication.
• More than moderate drinking averaged over the last month as assessed by history:
• o Moderate drinking is here defined as up to 3 drinks per week. The standard drink will be defined by the guidelines of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and will contain no more than 14 g of alcohol.
• Positive urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, cannabinoids, phencyclidine, propoxyphene, methadone, methaqualone, and alcohol at the screening and Day -1 tests.
• Any methadone use 14 days prior to screening, and up to Study Day -1.
• Has had a naltrexone implant in the past 24 months.
• Has received treatment with an extended naltrexone product (e.g. Vivitrol) in the past 12 months.

Sponsors & Collaborators

• Akyso Therapeutics, LLC: lead
• Laboratory Corporation of America: collaborator
• Cognitive Research Corporation: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

JBR Clinical Research

Salt Lake City, Utah, 84107, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; 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

Limitations and Caveats

This was a small Phase 1 safety and pharmacokinetic study with limited sample size and short follow-up duration. The study was not powered to detect differences in clinical efficacy or rare adverse events. Participants were healthy volunteers, which may limit generalizability to patients with opioid use disorder.

Results Point of Contact

• Title: Steven M. Cohen, MD, FACS
• Organization: Akyso Therapeutics, LLC

scohen@akyso.com

7272700659

Study Officials

• Todd Bertoch, MD

  Cenexel JBR

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The surgeon and the team performing the subcutaneous implant and removal will be unmasked. All other staff and subjects will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: January 22, 2024
• Study Start: June 24, 2024
• Primary Completion: April 18, 2025
• Study Completion: April 25, 2025
• Last Updated: April 28, 2026
• Results First Posted: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)