Clinical trial NCT02683577: Study to Evaluate a Dose of Telotristat Etiprate in Male and Female With Mild, Moderate and Severe Hepatic Insufficiency and Matched Healthy Subjects
Official title: A Phase 1, Open-label Study to Evaluate the Single Dose Pharmacokinetics of Telotristat Etiprate in Male and Female Subjects With Mild, Moderate and Severe Hepatic Impairment and Matched Subjects With Normal Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2016-02-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the protocol is to assess the pharmacokinetics, safety and tolerability of a single dose of telotristat etiprate in subjects with various stages of hepatic impairment compared to healthy control subjects.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) between 18 and 34 kg/m², inclusive, at screening. BMI 35 may be accepted in case of 3-point scored ascites.
* Minimum body weight of 50 kg.
* Vital signs (after 5 minutes resting in a supine position) that are within study specified ranges
* Female subjects of childbearing potential must agree to use an adequate double-barrier method of contraception during the study and for 30 days after discharge.
* Subjects with impaired hepatic function: Clinical diagnosis of chronic hepatic disease (stable for more than 3 months) with a documented history of underlying hepatic insufficiency and no acute episodes of illness within 30 days prior to Day -1, and no significant change in disease status (ie, up to 1 point in the Child-Pugh classification) from screening to Day -1.
* Control subjects with normal hepatic function: Clinical laboratory test results must be strictly within the normal laboratory reference ranges for liver function, and mean corpuscular volume (MCV) or, for other parameters, deemed as not clinically significant by the investigator.

Exclusion Criteria:

* Presence of clinically significant physical, laboratory, or Electrocardiogram (ECG) findings (with the exception of those parameters that are resulting from the underlying hepatic disease) that, in the opinion of the investigator, may interfere with any aspect of study conduct or interpretation of results.
* Clinically significant illness or disease as determined by medical history, including cardiac, pulmonary, hepatic (other than reason for their hepatic impairment), biliary, Gastrointestinal (GI), endocrinologic, or renal disorders, or cancer within the last 5 years (except localised or in situ nonmelanoma skin cancer), physical examination, clinical laboratory tests, and 12-lead ECGs.
* Receipt of any investigational agent or study drug within 30 days or 10 half-lives, whichever is longer, prior to dosing.
* Smoking more than 20 cigarettes (eg, 1 pack) per day or equivalent (eg, e-vapour cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum); unable or unwilling to refrain from smoking and tobacco use for 2 hours prior to dosing and 4 hours after dose administration.
* History of any serious adverse reaction or hypersensitivity to any inactive component of telotristat etiprate (ie, microcrystalline cellulose, croscarmellose sodium (disintegrant), talc, silicon dioxide, and magnesium stearate (nonbovine)).
* Existence of any surgical or medical condition that, in the judgment of the investigator and the sponsor's, medical monitor, might interfere with the absorption, distribution, metabolism, or excretion of telotristat etiprate.
* History of any major surgery within 6 months or anticipated surgery prior to Day -1.
* History of renal disease or significantly abnormal kidney function test.
* History of any active infection within 30 days prior to Day 1, if deemed clinically significant by the investigator.

Primary outcomes:
measure: Assessment of Maximum Observed Plasma Drug Concentration (Cmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours [h] post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of Time to Maximum Observed Plasma Concentration (Tmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of Area Under the Plasma Concentration Time Curve From 0 to Time t Corresponding to the Last Quantifiable Concentration (AUC[0-tlast]) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC[0-inf]) for Telotristat Ethyl
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of Cmax for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of Tmax for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group and Comparison Between Each Hepatic Impairment Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of AUC(0-tlast) for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of AUC(0-inf) for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of t1/2 for Telotristat Ethyl and LP-778902 (Active Metabolite)
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
measure: Assessment of Apparent Terminal Elimination Rate Constant (λz) for Telotristat Ethyl and LP-778902 (Active Metabolite)
timeFrame: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Secondary outcomes:
Other outcomes:
Locations:
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Exploratory Medicine
city: Bucharest
country: Romania
facility: ARENSIA Exploratory Medicine
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: