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

NCT ID: NCT03442725

Last Updated: 2020-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-09
• Study Completion Date: 2018-05-13

Brief 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.

Conditions

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Severely decreased renal function group

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).

Group Type: EXPERIMENTAL

Telotristat etiprate

Intervention Type: DRUG

Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.

Normal renal function group

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).

Group Type: ACTIVE_COMPARATOR

Telotristat etiprate

Intervention Type: DRUG

Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.

Mildly decreased renal function group

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).

Group Type: EXPERIMENTAL

Telotristat etiprate

Intervention Type: DRUG

Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.

Moderately decreased renal function group

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).

Group Type: EXPERIMENTAL

Telotristat etiprate

Intervention Type: DRUG

Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.

Interventions

Telotristat etiprate

Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.

Intervention Type: DRUG

Other Intervention Names

Xermelo®

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

A.T.C. s.a., Clinical Pharmacology Unit, CHU Sart-Tilman

Liège, , Belgium

CRS Clinical Research Services Kiel GmbH

Kiel, , Germany

ARENSIA Exploratory Medicine Phase I Unit, Republican Clinical Hospital

Chisinau, , Moldova

ARENSIA Unit in Spitalul de Nefrologie

Bucharest, , Romania

Countries

Belgium; Germany; Moldova; Romania

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2017-003948-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D-FR-01017-002

Identifier Type: -

Identifier Source: org_study_id