Pharmacokinetic and Safety Study of Naltrexone Release From Subcutaneous BICX104 Pellets Compared to Vivitrol Injections

• BICX104 (Drug): Erodable implantable pellet containing 1 g naltrexone and 11 mg magnesium stearate.
• Vivitrol (Drug): Intramuscular injection containing 380 mg of naltrexone.

Primary outcomes

• Pharmacokinetic parameter: Cmax. [140 Days]: Maximum observed mean plasma concentration \[Cmax\] of naltrexone and 6-beta-naltrexol.
• Pharmacokinetic parameter: Tmax. [140 Days]: Time to mean maximum observed drug concentration (Tmax) of naltrexone and 6-beta-naltrexol.
• Pharmacokinetic parameter: Css. [140 Days]: Changes in the mean observed steady state plasma concentration \[Css\] of naltrexone and 6-beta-naltrexol.
• Pharmacokinetic parameter: AUC [140 Days]: Area Under the Plasma Concentration Versus Time Curve (AUC) of naltrexone and 6-beta-naltrexol.
• Pharmacokinetic parameter: Tlast ≥ 1ng/ml naltrexone. [140 Days]: Time of Last Quantifiable Plasma Concentration (Tlast) of naltrexone greater than or equal to 1ng/ml.
• Pharmacokinetic parameter: Tlast. [140 Days]: Time of Last Quantifiable Plasma Concentration (Tlast) of naltrexone and 6-beta-naltrexol.

Secondary outcomes

• Safety Parameter: AEs [168 Days]: Incidence and severity of adverse events (AEs)

Sex: All, ages: 18 Years to 50 Years, accepts healthy volunteers

Inclusion Criteria:

1. Willing and able to provide informed consent.
2. Female or male subjects aged 18-50 years old.
3. Without current non-remitted DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) - Substance Use Disorders diagnoses; subjects with a sustained remission diagnosis are not excluded.
4. In good health, as determined by the study physician, based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests within normal ranges, to permit treatment.
5. Weight of 100-180 pounds, and a BMI of 18.5 to 30 kg/m2, inclusive.
6. Must agree to comply with all study requirements and be willing to complete entire study.
7. Females of childbearing potential and males willing to practice an effective method(s) of birth control for the duration of participation in the study (<1% failure rate per year).

Exclusion Criteria:

1. Is pregnant, is planning to become pregnant or breastfeed infants during the study.
2. Is currently treated with naltrexone or has had a naltrexone implant in the past 2 years or received Vivitrol treatment in the past year.
3. Clinically significant medical/psychological condition or abnormality at screening (i.e., physical examination, electrocardiogram \[ECG\], hematology or blood chemistry evaluation, or urinalysis findings), including any diagnosis of Hepatitis B, Hepatitis C or HIV infection.
4. Presence of opiates, cocaine, methamphetamine or other significant drugs of abuse in the urine (as determined by urine drug test).
5. Any active hepatitis or hepatic failure or dysfunction evidenced by the following: aspartate transaminase (AST) or alanine transaminase (ALT) higher than 1.5 times the upper limit of normal (1.5xULN), hyperbilirubinemia (bilirubin >10% above ULN), creatine phosphokinase (CPK) higher than 2.5xULN, prolonged prothrombin time (international normalized ratio ≥1.7), ascites, or esophageal variceal disease.
6. Manifestation of suicidal ideation, psychotic symptoms (including significant violent behavior), or psychiatric or neurological disorders that would compromise ability to complete the study.
7. Participation in a methadone program currently or within past 3 years, or 3 or more previous medically supervised detoxification treatments in past 3 years.
8. If a healthy volunteer fails one naloxone challenge, the subject will not be suitable for the study. The only exceptions will be made when a 'false positive' test result is received for the first test.
9. Intolerance and/or hypersensitivity to naltrexone, naloxone, or polylactide-co-polymers such as polylactide-co-glycolide (PLG).
10. Participation in a clinical trial within 30 days of screening.
11. Has a condition which requires or may require treatment with opioid based medication.
12. Is prone to skin rashes, irritation or has a chronic skin condition.
13. Alcohol Use Disorder diagnosis.
14. Has a predisposition to poor response to an implant site reaction, as judged by the study physician.
15. Has a history of keloid formation, connective tissue disease, e.g., scleroderma, or history of recurrent MRSA infections.

NIH grants: UG3DA047925