Study to Compare a Dose of Telotristat Etiprate in Subjects With Renal Impairment With Matched Subjects With Normal Renal Function

Ipsen

Status and phase: Completed; Phase 1

Conditions: Renal Impairment

Treatments: Drug: Telotristat etiprate

Study type: Interventional

Funder types: Industry

Identifiers

NCT03442725

2017-003948-20 (EudraCT Number)

D-FR-01017-002

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 4 patient groups

Severely decreased renal function group

Experimental group

Description:

Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).

Treatment:

Drug: Telotristat etiprate

Normal renal function group

Active Comparator group

Description:

Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).

Treatment:

Drug: Telotristat etiprate

Mildly decreased renal function group

Experimental group

Description:

Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).

Treatment:

Drug: Telotristat etiprate

Moderately decreased renal function group

Experimental group

Description:

Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).

Treatment:

Drug: Telotristat etiprate