iSTEP-N 101b: Pharmacokinetics and Safety Study of Low- and High-Dose Naltrexone Implants vs Monthly Vivitrol in Healthy Volunteers

NCT07064564 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: iSTEP-N 101bUH3DA048338
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

Brief Summary

This Phase 1b clinical study is evaluating iSTEP-N, an investigational extended-release implant containing naltrexone, a medication used to block the effects of opioids. The implant is placed under the skin of the thigh and is designed to release medication continuously over many months. The main purpose of the study is to measure blood levels of naltrexone over time after administration of two different doses of the iSTEP-N implant and to compare those levels with the blood levels achieved by Vivitrol®, an FDA-approved injectable extended-release naltrexone given once every month. The study will enroll healthy adult volunteers aged 18 to 65 years. Participants will be randomly assigned to one of three groups:

• Low-dose iSTEP-N implant
• High-dose iSTEP-N implant
• Monthly Vivitrol injections Participants will be followed closely for approximately 12 months to measure medication levels and monitor safety, side effects, and overall health. The study will help determine whether the iSTEP-N implant can maintain naltrexone levels comparable to or higher than those achieved with monthly injections, especially during periods when protection from relapse is most important. Participants who receive an iSTEP-N implant and still have detectable implant material or measurable medication levels at the end of the first year may continue in a long-term follow-up period lasting up to two additional years. During this period, researchers will monitor how long the implant remains detectable and how long medication continues to be released. If the implant remains after two years, participants may choose to have it surgically removed or simply end study participation. The study is sponsored by Akyso Therapeutics, LLC, with clinical operations conducted at a dedicated clinical research center and oversight provided by an independent Institutional Review Board. All participants undergo screening examinations to confirm eligibility and are carefully monitored throughout participation. Results from this study will help determine the appropriate dose of iSTEP-N for future clinical trials and support development of long-acting treatment options for opioid use disorder that may reduce the need for frequent injections.

Conditions

Opioid Use Disorder

Keywords

naltrexone; biopin; oud; implant; opioid use disorder; extended-release; vivtrol

Outcome Measures

Primary Outcomes (1)

• Average plasma naltrexone concentration on the last day of each 4-week interval through Week 52

  The average of plasma naltrexone concentrations measured on the final day of each 4-week period through 12 months. This composite measure is used to assess sustained drug exposure and compare treatment arms.

  Day 28, 56, 84, 112, 140, 168, 196, 224, 252, 280, 308, and 336

Secondary Outcomes (6)

• Area Under the Curve (AUC) for Naltrexone

  Day 1 through Week 52

• Maximum plasma concentration (Cmax) of naltrexone

  Day 1 through Week 52

• Minimum plasma concentration (Cmin) of naltrexone

  Day 1 through Week 52

• Plasma concentration of 6β-naltrexol (naltrexone metabolite)

  Day 1 through Week 52

• Number of participants with treatment-emergent adverse events

  Day 1 through Week 52

Study Arms (3)

iSTEP-N High Dose Implant

EXPERIMENTAL

Participants in this arm will receive a single subcutaneous implant of iSTEP-N at a high dose level (14.4 grams of naltrexone) on Day 1. Participants will undergo pharmacokinetic and safety evaluations for 12 months. Participants with a detectable implant or measurable naltrexone levels at the end of this period may continue in a longer-term follow-up phase. Intervention: Drug: iSTEP-N Naltrexone Implant - High Dose Single 14.4 g subcutaneous implant administered on Day 1.

Drug: Naltrexone implant, 14.4 grams

Low-Dose iSTEP-N Implant

EXPERIMENTAL

Arm Description (Revised - Low-Dose iSTEP-N) Participants in this arm will receive a single subcutaneous implant of iSTEP-N containing 9.6 grams of naltrexone on Day 1. Participants will undergo pharmacokinetic and safety evaluations for 12 months. Participants with a detectable implant or measurable naltrexone levels at the end of this period may continue in a longer-term follow-up phase. Intervention: Drug: iSTEP-N Naltrexone Implant (Low Dose) Single 9.6 g subcutaneous implant administered on Day 1.

Drug: Naltrexone implant, 9.6 grams

Vivitrol Injection

ACTIVE COMPARATOR

Participants in this arm will receive 380 mg of extended-release naltrexone (Vivitrol) by intramuscular injection every 4 weeks for 12 months. Blood samples will be collected to evaluate pharmacokinetics and safety. Intervention: Drug: Vivitrol (Extended-Release Naltrexone Injection) 380 mg IM injection every 4 weeks for 52 weeks.

Drug: Extended-release naltrexone injection, 380 mg

Interventions

Naltrexone implant, 9.6 grams DRUG

Subcutaneous bioresorbable implant containing 9.6 grams of naltrexone, inserted into the thigh on Day 1 and designed to release drug steadily over 12 months.

Low-Dose iSTEP-N Implant

Naltrexone implant, 14.4 grams DRUG

Subcutaneous bioresorbable implant containing 14.4 grams of naltrexone, inserted into the thigh on Day 1 and designed to release drug steadily over 12 months.

iSTEP-N High Dose Implant

Extended-release naltrexone injection, 380 mg DRUG

Intramuscular injection of 380 mg extended-release naltrexone (Vivitrol), administered every 4 weeks for 12 months as the active comparator.

Vivitrol Injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for the study:
• Healthy adult male or female volunteers, ages 18 to 55 years.
• Able and willing to provide written informed consent prior to any study procedures.
• In good general health as determined by medical history, physical examination, vital signs, ECG, and laboratory tests (chemistry, hematology, and coagulation).
• No clinically significant abnormalities in lab results, as determined by the investigator.
• Negative urine drug screen for opioids, cocaine, amphetamines, benzodiazepines, cannabinoids, and other substances of abuse.
• Negative breath alcohol test at screening and baseline.
• Negative naloxone challenge test, indicating no physiological opioid dependence.
• For females of childbearing potential:
• Negative serum pregnancy test at screening and Day 0.
• Agreement to use acceptable contraception (including oral hormonal contraception) for the duration of the study.
• For males with female partners of childbearing potential:
• Agreement to use effective contraception throughout the study.
• Negative infectious disease panel, including HIV, hepatitis B surface antigen, and hepatitis C antibody.
• No evidence of suicidal ideation or behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening.

You may not qualify if:

• Participants who meet any of the following conditions will be excluded:
• Current or recent history (past 12 months) of opioid use disorder, substance use disorder, or alcohol dependence.
• Positive urine drug test or breath alcohol test at screening or prior to randomization.
• Failure of the naloxone challenge test, indicating possible physical opioid dependence.
• Use of any investigational drug or device within 30 days prior to screening.
• Use of any opioid-containing medications (prescription or OTC) within 14 days prior to screening.
• Known hypersensitivity or allergy to naltrexone, polycaprolactone (PCL), polylactic acid (PLA), polymeric implants, or any other component of the study drug.
• History of chronic pain, neurological or psychiatric disorders, or any condition requiring regular use of medications.
• Active medical condition or past medical history that, in the opinion of the investigator, could interfere with the study or pose an undue risk, including:
• Cardiovascular disease
• Hepatic or renal impairment
• Gastrointestinal disorders affecting absorption
• Respiratory disease
• Seizure disorder
• Autoimmune or inflammatory disorders

Sponsors & Collaborators

• Akyso Therapeutics, LLC: lead
• National Institute on Drug Abuse (NIDA): collaborator
• Cenexel JBR: collaborator
• Fast-Track Drugs & Biologics, LLC: collaborator
• Aliri Bioanalysis: collaborator
• Ardena: collaborator
• Element Analytics: collaborator

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

Study Officials

• Todd Bertoch

  MD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven Cohen, MD

CONTACT

727-270-0659; scohen@akyso.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study. No masking is used due to the differences in route of administration between the implant and injectable comparator.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomized to one of three parallel groups: (1) low-dose iSTEP-N implant, (2) high-dose iSTEP-N implant, or (3) monthly Vivitrol injections. All groups are followed concurrently for 12 months to assess pharmacokinetics and safety. Participants who receive an iSTEP-N implant may continue in a longer-term follow-up phase to evaluate implant persistence and extended pharmacokinetics.

Study Record Dates

• First Submitted: July 5, 2025
• First Posted: July 14, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 31, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share