Nalmefene implant in healthy volunteers

Inclusion Criteria:

\- Subjects must meet all of the following criteria to be included in the study:

1. Male or female, non-smoker, ≥18 and ≤55 years of age, with body mass index (BMI) \>18.5 and \<35.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
2. Healthy as defined by:

   1. the absence of clinically significant illness and surgery within 4 weeks prior to implant insertion.
   2. the absence of clinically significant history of dermatologic, neurological, musculoskeletal, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
3. Female subjects of non-childbearing potential must be:

   1. post-menopausal with confirmation by documented follicle-stimulating hormone (FSH) test; or
   2. surgically sterile .
4. Female subjects of childbearing potential who are sexually active with a non-sterile male partner must be willing to use an acceptable contraceptive methods throughout the study and for 30 days after the implant is removed:
5. Male subjects who are not vasectomized for at least 3 months prior to implant insertion and who are sexually active with a female partner of childbearing potential must be willing to use an acceptable contraceptive methods from implant insertion and for 30 days after the implant is removed:

6 Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria:

* Subjects to whom any of the following applies will be excluded from the study:

  1. Any clinically significant abnormal finding at physical examination at screening.
  2. Clinically significant history of or current evidence of suicidal ideation or active suicidal behavior as based on the C-SSRS.
  3. Clinically significant history or current evidence of depression as based on the MADRS.
  4. Clinically significant abnormal laboratory test results or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening.
  5. Positive pregnancy test or lactating female subject.
  6. Positive urine drug screen, urine cotinine test, or alcohol breath test.
  7. Known medically significant intolerance or allergic reactions to nalmefene or to ethylene vinyl acetate
  8. Hypersensitivity to lidocaine or other local anesthetics of the amide type, epinephrine, antiseptic solution
  9. Clinically significant ECG abnormalities or vital signs abnormalities
  10. History of drug use within 1 year prior to screening or recreational use of marijuana within 1 month
  11. History of alcohol abuse within 1 year prior to screening
  12. Use of medications for the timeframes specified below:

      1. depot injection or implant within 3 months prior to implant insertion;
      2. any drug known to induce hepatic drug metabolism within 30 days prior to implant insertion;
      3. prescription medications within 14 days prior to implant insertion;
      4. any vaccine within 14 days prior to implant insertion;
      5. over-the-counter medications and natural health products within 7 days prior to implant insertion
  13. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to implant insertion,
  14. Donation of plasma within 7 days prior to dosing or donation or
  15. Intolerant to venipuncture and/or have difficulty with venous access.
  16. History of wound healing problems.
  17. Lymphedema, scarring, or tattoos on his/her inner upper arms within 2 months prior to screening or a history of keloid scarring.
  18. Any dermatologic disorder, including cancer, that precludes the safety of the implant
  19. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.