A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder
Condition: Opioid Use Disorder
MeSH terms: Opioid-Related Disorders; Substance-Related Disorders
Intervention: ASP8062; Placebo ASP8062; buprenorphine/naloxone
Intervention description: Oral; Oral; Sublingual
Intervention MeSH terms: Buprenorphine; Buprenorphine, Naloxone Drug Combination; ASP8062; Naloxone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Suboxone®; Opioid Use Disorder; buprenorphine/naloxone; ASP8062; pharmacokinetic

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has a body mass index range of 18 to 36 kg/m^2, inclusive and weighs at least
             50 kg at screening.

          -  Subject has a diagnosis of moderate or severe opioid use disorder (OUD) according to
             the Diagnostic and Statistical Manual of Mental Disorders, edition 5 (DSM-5) at
             screening.

          -  Subject tests positive for opioids at screening and/or on day -1 or subject shows
             signs of opioid withdrawal on day -1.

          -  Subject is willing to take buprenorphine/naloxone and is not taking buprenorphine or
             buprenorphine/naloxone at screening.

          -  Female subject 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 30 days after final investigational product (IP)
                  administration.

          -  Female subject must agree not to breastfeed starting at screening and throughout the
             study period and for 30 days after final IP administration.

          -  Female subject must not donate ova starting at first dose of IP and throughout the
             study period and for 30 days after final IP administration.

          -  Male subject with female partner(s) of childbearing potential (including breastfeeding
             partner) must agree to use contraception throughout the study period and for 90 days
             after final IP administration.

          -  Male subject must not donate sperm during the treatment period and for 90 days after
             final IP administration.

          -  Male subject with pregnant partner(s) must agree to remain abstinent or use a condom
             and spermicide for the duration of the pregnancy throughout the study period and for
             90 days after final IP administration.

          -  Subject agrees not to participate in another interventional study while participating
             in the present study.

          -  Subject 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 11 and 12.

        Exclusion Criteria:

          -  Subject has received any investigational therapy within 28 days or 5 half-lives,
             whichever is longer, prior to screening.

          -  Subject has any condition which makes the subject unsuitable for study participation.

          -  Female subject who has been pregnant within 6 months prior to screening or
             breastfeeding within 3 months prior to screening.

          -  Subject has a known or suspected hypersensitivity to ASP8062, buprenorphine, naloxone
             or any components of the formulations used.

          -  Subject has had previous exposure with ASP8062.

          -  Subject has any of the liver function tests (alkaline phosphatase [ALP], alanine
             aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase
             and total bilirubin [TBL]) > 2 × upper limit of normal (ULN) on day -1. In such a
             case, the assessment may be repeated once.

          -  Subject 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.

          -  Subject 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.

          -  Subject has current or recent diagnosis (within the last 12 months) of moderate or
             severe alcohol, sedative, hypnotic, anxiolytic, cocaine or any other substance use
             disorder (except for opioids, caffeine, tobacco or nicotine) according to the DSM-5 at
             screening.

          -  Subject has a history or presence of any clinically significant psychiatric disorders
             such as, bipolar 1, schizophrenia, schizoaffective disorder or major depressive
             disorders.

          -  Subject tests positive for alcohol, benzodiazepine or methadone on day -1. Subject
             tests positive for buprenorphine on day -1.

          -  Subject has had recent suicidal ideation within the last 12 months or subject who is
             at significant risk to commit suicide using the Columbia-Suicide Severity Rating Scale
             (C-SSRS) at screening or since the last visit on day -1.

          -  Subject has/had febrile illness or symptomatic, viral, bacterial (including upper
             respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day
             -1.

          -  Subject has any clinically significant abnormality following physical examination,
             electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or
             on day -1.

          -  Subject has a mean pulse < 45 or > 110 beats per minute (unless out of range [> 110
             beats per minute] pulse is deemed to be secondary to opioid withdrawal); mean systolic
             blood pressure > 150 mmHg; mean diastolic blood pressure > 95 mmHg (unless out of
             range blood pressure is deemed to be secondary to opioid withdrawal)(measurements
             taken in duplicate after subject has been resting in the supine position for at least
             5 minutes; pulse will be measured automatically) on day -1. If the mean blood pressure
             exceeds the limits above, 1 additional duplicate may be taken.

          -  Subject has a mean corrected QT interval using Fridericia's formula (QTcF) of > 450
             msec (for male subjects) and > 470 msec (for female subjects) on day -1. If the mean
             QTcF exceeds the limits above, 1 additional duplicate ECG may be taken.

          -  Subject has used any prescribed drugs, vitamins and natural or herbal remedies
             (including, St. John's Wort) in the 2 weeks prior to first IP administration, except
             for rescue medications, milk of magnesia, acetaminophen, topical dermatological
             products, including corticosteroid products, hormonal contraceptives and hormone
             replacement therapy (HRT).

          -  Subject has used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3
             months prior to day -1.

          -  Subject has had significant blood loss or 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.

          -  Subject has a positive serology test for antibodies to human immunodeficiency virus
             type 1 and/or type 2, acute hepatitis B virus infection or acute hepatitis C virus
             infection, excluding asymptomatic hepatitis C virus infection at screening.

          -  Subject 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.

          -  Subject is an employee of Astellas, the study-related contract research organizations
             or the clinical unit.

          -  Subject has used any inducer of CYP2C8, 2C9 or 3A4-related metabolism (e.g.,
             barbiturates, rifampin, aprepitant, ritonavir, apalutamide, carbamazepine,
             enzalutamide, mitotane, phenytoin, rifampin, St. John's wort, bosentan, efavirenz,
             etravirine, phenobarbital, primidone, armodafinil, modafinil, and rufinamide) in the 3
             months prior to day -1.