Study to Compare a Dose of Telotristat Etiprate in Subjects With Renal Impairment With Matched Subjects With Normal Renal Function
Condition: Renal Impairment
MeSH terms: Renal Insufficiency
Intervention: Telotristat etiprate
Intervention description: Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Renal excretion is a minor elimination route of telotristat etiprate. So this trial is
      intended to assess the drug behaviour in subjects with decreased renal function.

      This is a staged study with Part B contingent upon the results of Part A. Part A will enrol a
      total of 16 subjects, eight with severely impaired renal function and eight healthy subjects.
      Part B with enrol a total of 16 subjects, eight subjects in each additional renal function
      group, i.e. mildly impaired renal function group and moderately impaired group.
    

Eligibility criteria:

        Inclusion Criteria:

        All subjects:

          -  Provision of written informed consent prior to any study related procedure.

          -  Men and women enrolling in the study must be at least 18 years of age at the time of
             giving informed consent.

          -  Women of childbearing potential must agree to use an adequate double-barrier method of
             contraception during the study and for 30 days after discharge.

          -  Men must agree to use an adequate, double barrier method of contraception during the
             study and for 30 days after discharge.

        Additionally, for subjects with renal impaired function:

          -  Clinical diagnosis of renal impaired function that has been stable for more than 3
             months prior to dosing

          -  Renal impaired function classified as mild, moderate, or severe.

          -  Under stable medication regimen, i.e. not starting new therapy(ies) or significant
             changing dosage(s) within at least 1 month prior to dosing, as determined by the
             investigator.

          -  Stable and appropriately managed relative to chronic diseases (e.g. diabetes,
             hypertension) as determined by medical history, physical examination, ECGs, and
             clinical laboratory tests.

        Additionally, for healthy subjects with normal renal function:

          -  Each subject will be demographically-matched to one of the subjects with severely
             impaired renal function for gender, age (± 10 years), BMI (± 20%).

          -  Clinical laboratory test results must be strictly within the normal laboratory
             reference ranges for urea, creatinine, protein, and albumin.

        Exclusion Criteria:

        All subjects:

          -  Existence of any surgical or medical condition that, in the judgment of the
             investigator, might interfere with the absorption, distribution, metabolism, or
             excretion of telotristat etiprate (including bariatric surgery, or any other
             gastrointestinal surgery, excepting appendectomy and hernia repair, which are
             acceptable).

          -  History of any major surgery within six months or anticipated surgery prior to Day-1.

          -  Patients with hereditary problems of galactose intolerance (lactase deficiency or
             glucose-galactose malabsorption).

          -  History of any active infection within 30 days prior to Day-1, if deemed clinically
             significant by the investigator.

          -  Positive hepatitis panel results (including hepatitis B surface antigen and hepatitis
             virus C ribonucleic acid).

          -  Positive results for human immunodeficiency virus, or who has received diagnosis for
             acquired immunodeficiency syndrome.

          -  Positive urine screen for drugs of abuse (not including cotinine).

          -  Consumption of alcohol within 48 hours prior to Day-1 (as confirmed by alcohol breath
             screen) and for the duration of the confinement period.

          -  Smoking more than ten cigarettes per day or equivalent; unable or unwilling to refrain
             from smoking and tobacco use for two hours prior to dosing and four hours after dose
             administration.

          -  Consumption of caffeine- and/or xanthine-containing products (e.g. cola, coffee, tea,
             chocolate) on Day-1 until 24 hours postdose.

          -  Consumption of grapefruit, Seville oranges, and grapefruit- or Seville
             orange-containing products within 72 hours prior to Day-1 and for the duration of the
             confinement period.

          -  Use of any medication (prescription or over-the-counter), Chinese herbal medications
             or herbal tea, energy drinks, herbal products (e.g. St. John's wort, garlic), or
             supplements/supra therapeutic doses of vitamins within 14 days prior to Day-1 and up
             to Day 4 after dosing, apart from those approved by the investigator.

          -  Women who are breastfeeding or are planning to become pregnant during the study.

        Additionally, for renal impaired subjects:

          -  Clinically significant physical (e.g. oedema in heavy subjects with renal impaired
             function), laboratory, or ECG findings (apart from those parameters which are related
             to impaired renal function or underlying disease e.g. diabetes, hypertension) that, in
             the opinion of the investigator, may interfere with any aspect of the study conduct or
             interpretation of the results.

          -  Glycated haemoglobin A1c ≥ 9%.

        Additionally, for healthy subjects with normal renal function:

          -  Clinically significant illness or disease including cardiac, pulmonary,
             hepato-biliary, gastrointestinal, or endocrinology, or cancer within the last 5 years
             (except localised or in situ non-melanoma skin cancer), as determined by medical
             history, physical examination, laboratory tests, and 12-lead ECGs.

          -  Clinically significant physical, laboratory, or ECG findings that, in the opinion of
             the investigator, may interfere with any aspect of the study conduct or interpretation
             of the results.

          -  History of renal disease.

          -  History of alcohol or drug abuse within 2 years prior to screening.