A Bioavailability Study With Alternate Methods of Administration of Naloxegol Tablets, and Solution
Condition: Bioavailability; Healthy Subjects
Intervention: Naloxegol 25 mg tablet, crushed, suspended in water, given orally; Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube; Naloxegol 25 mg (10 mL oral solution); Naloxegol 25 mg tablet, given orally
Intervention description: naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally; naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube; naloxegol 25 mg (10 mL oral solution); naloxegol 25 mg (1 tablet) whole tablet, given orally
Intervention MeSH terms: Naloxegol
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: naloxegol tablet crushed; naloxegol oral solution; naloxegol whole tablet; relative bioavailability; Phase I; healthy subjects

Summary:

      This clinical study is an open-label, randomized, 4-period, 4-treatment, crossover,
      single-center, single-dose bioavailability study with alternate methods of administration of
      crushed naloxegol tablets, 25 mg and of a naloxegol solution formulation, 25 mg, compared to
      whole naloxegol tablets, 25 mg, in healthy subjects.

      The main objective of this study is to determine the bioavailability of each of three
      alternative methods of naloxegol administration compared to whole naloxegol tablets given
      orally by assessment of the primary pharmacokinetic (PK) parameters of naloxegol
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male and female subjects aged 18 to 55 years with suitable veins for
             cannulation or repeated venipuncture.

          -  Females must have a negative pregnancy test at screening and on admission to the
             clinical unit, must not be lactating and must be of non childbearing potential,
             confirmed at screening by fulfilling one of the following criteria:

               -  Post-menopausal defined as amenorrhea for at least 12 months or more following
                  cessation of all exogenous hormonal treatments and follicle-stimulating hormone
                  (FSH) levels in the post-menopausal range.

               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy; but not tubal ligation.

          -  Have a body mass index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weigh at least
             50 kg and no more than 100 kg inclusive.

          -  Able to understand, read and speak the German language.

        Exclusion Criteria:

          -  History of any clinically significant disease or disorder which, in the opinion of the
             investigator, may either put the potential subject at risk because of participation in
             the study, or influence the results or the potential subject's ability to participate
             in the study.

          -  Current smokers or those who have smoked or used nicotine products within the previous
             3 months.

          -  Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks
             prior to the first administration of IMP.

        Drugs include known CYP3A4 and/or P-gp inhibitors and inducers, e.g., diltiazem, verapamil,
        and erythromycin

        - Use of any prescribed or non-prescribed medication including antacids, analgesics (other
        than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600
        times the recommended daily dose) and minerals during 2 weeks prior to the first
        administration of IMP or longer if the medication has a long half-life.

        For females, hormonal replacement therapy is not allowed.

          -  Subject with a relevant history of a suicide attempt or suicidal behavior. Any recent
             suicidal ideation within the last 6 months (a level of 4 or 5), or who are at
             significant risk to commit suicide, as judged by the investigator using the
             Columbia-Suicide Severity Rating Scale (C-SSRS).

          -  Applicable to subjects willing to participate in genetic research: Non-leukocyte
             depleted whole blood transfusion within 120 days of the date of the genetic sample
             collection or previous bone marrow transplant.