A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants
Condition: Opioid Use Disorder
MeSH terms: Opioid-Related Disorders
Intervention: ASP8082; morphine; Placebo
Intervention description: oral; oral; oral
Intervention MeSH terms: Morphine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Opioid Use Disorder; pharmacokinetic; ASP8062; morphine

Summary:

      The primary purpose of this study was to assess the safety and tolerability of multiple doses
      of ASP8062 or placebo alone and in combination with a single dose of morphine.

      This study also assessed the potential for pharmacokinetic interaction between ASP8062 and
      morphine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is a recreational opioid user who has used opioids for nontherapeutic
             (recreational) purposes on at least 10 occasions within their lifetime, with at least
             1 opioid use in the last 90 days.

          -  Participant has a body mass index (BMI) range of 18 to 36 kg/m^2, inclusive and weighs
             at least 50 kg at screening.

          -  Female participant is not pregnant and at least 1 of the following conditions apply:

               -  Not a woman of childbearing potential (WOCBP)

               -  WOCBP who agrees to follow the contraceptive guidance from the time of informed
                  consent through at least 28 days after final investigational product (IP)
                  administration.

          -  Female participant must agree not to breastfeed starting at screening and throughout
             the study period and for 28 days after final IP administration.

          -  Female participant must not donate ova starting at first dose of IP and throughout the
             study period and for 28 days after final IP administration.

          -  Male participant with female partner(s) of childbearing potential (including
             breastfeeding partner[s]) must agree to use contraception throughout the treatment
             period and for 90 days after final IP administration.

          -  Male participant must not donate sperm during the treatment period and for 90 days
             after final IP administration.

          -  Male participant with a pregnant partner(s) must agree to remain abstinent or use a
             condom with spermicide for the duration of the pregnancy throughout the study period
             and for 90 days after final IP administration.

          -  Participant agrees to not participate in another interventional study while
             participating in the present study.

        Exclusion Criteria:

          -  Participant has received any investigational therapy within 28 days or 5 half-lives,
             whichever is longer, prior to screening.

          -  Participant has any condition which makes the participant unsuitable for study
             participation.

          -  Female participant who has been pregnant within 6 months prior to screening or
             breastfeeding within 3 months prior to screening.

          -  Participant has a known or suspected hypersensitivity to ASP8062 or morphine and/or
             other opioids, or any components of the formulations used.

          -  Participant has had previous exposure with ASP8062.

          -  Participant has any of the liver function tests (alkaline phosphatase [ALP], alanine
             aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase
             and total bilirubin [TBL]) ≥ 1.5 × upper limit of normal (ULN) on day -1. In such a
             case, the assessment may be repeated once.

          -  Participant has any clinically significant history of allergic conditions (including
             drug allergies, asthma or anaphylactic reactions, but excluding untreated,
             asymptomatic, seasonal allergies) prior to first IP administration.

          -  Participant has any history or evidence of any clinically significant cardiovascular,
             gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic,
             urologic, pulmonary, neurologic, dermatologic, renal and/or other major disease or
             malignancy with exception of history of cholecystectomy.

          -  Participant has a history of moderate or severe use disorder for any substance other
             than caffeine or tobacco (based on the Diagnostic and Statistical Manual of Mental
             Disorders, edition 5 (DSM-5) criteria).

          -  Participant has a history or presence of any clinically significant psychiatric
             disorders such as, bipolar 1, schizophrenia, schizoaffective disorder or major
             depressive disorders.

          -  Participant has had recent suicidal ideation within the last 12 months or participant
             who is at significant risk to commit suicide using the Baseline/Screening
             Columbia-suicide severity rating scale (C-SSRS) at screening and the Since Last Visit
             C-SSRS on day -1.

          -  Participant has/had febrile illness or symptomatic, viral, bacterial (including upper
             respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day
             -1.

          -  Participant has any clinically significant abnormality following an investigator's
             review of the physical examination, ECG and protocol-defined clinical laboratory tests
             at screening or on day -1.

          -  Participant has a mean pulse < 50 or > 90 bpm; mean systolic blood pressure > 150
             mmHg; mean diastolic blood pressure > 95 mmHg (measurements taken in duplicate after
             participant has been resting in the supine position for at least 5 minutes) on day -1.
             If the mean blood pressure exceeds the limits above, 1 additional duplicate may be
             taken.

          -  Participant has a mean corrected QT interval using Fridericia's formula (QTcF) of >
             450 msec (for male participants) and > 470 msec (for female participants) on day -1.
             If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.

          -  Participant has a positive test for amphetamines, barbiturates, benzodiazepines,
             cocaine, phencyclidine, alcohol and/or opiates on day -1. Positive
             tetrahydrocannabinol is not exclusionary and a cannabis intoxication evaluation will
             be performed. Participant may be reconsidered.

          -  Participant has used any prescribed or nonprescribed drugs (including vitamins and
             natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to first IP
             administration, except for occasional use of acetaminophen (up to 2 g/day), topical
             dermatological products, including corticosteroid products, hormonal contraceptives
             and hormone replacement therapy (HRT).

          -  Participant must be willing to abstain from smoking (including use of
             tobacco-containing products and nicotine or nicotine-containing products [e.g.,
             electronic vapes]) from at least 1 hour predose through at least 8 hours postdose on
             days 9 and 10.

          -  Participant has used any inducer of metabolism (e.g., barbiturates and rifampin) in
             the 3 months prior to day -1.

          -  Participant has had significant blood loss, donated approximately 500 mL of whole
             blood (excluding plasma donation) within 56 days prior to screening or donated plasma
             within 7 days prior to day -1.

          -  Participant has a positive serology test for hepatitis B surface antigen, hepatitis C
             virus antibodies or antibodies to human immunodeficiency virus (HIV) type 1 and/or
             type 2 at screening.

          -  Participant has loss of ability to freely provide consent through imprisonment or
             involuntary incarceration for treatment of either a psychiatric or physical (e.g.,
             infectious disease) illness.

          -  Participant is an employee of Astellas, the study-related contract research
             organizations (CROs) or the clinical unit.