- ICH GCP
- US Clinical Trials Registry
- 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
January 24, 2019 updated by: Ipsen
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
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Chisinau, Moldova, Republic of, MD-2025
- ARENSIA Exploratory Medicine
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Bucharest, Romania, 050159 Distr
- ARENSIA Exploratory Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Telotristat etiprate 500 mg
1 single oral dose (2 x 250-mg tablets)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of Maximum Observed Plasma Drug Concentration (Cmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
Time Frame: 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).
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Blood was sampled for the purpose of determining pharmacokinetic (PK) parameters for total telotristat ethyl using a validated, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method.
The method was selective, linear, precise and accurate within the range from 0.5 to 500 nanograms per millilitre (ng/mL) for telotristat ethyl and the lower limit of quantification (LoQ) was 0.5 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
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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).
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Assessment of Time to Maximum Observed Plasma Concentration (Tmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
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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).
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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
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
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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).
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Assessment of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC[0-inf]) for Telotristat Ethyl
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
AUC(0-inf) was not determined when the apparent terminal elimination half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%.
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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).
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Assessment of Cmax for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group
Time Frame: 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).
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Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
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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).
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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
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
|
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).
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Assessment of AUC(0-tlast) for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
|
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).
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Assessment of AUC(0-inf) for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL.
Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
AUC(0-inf) was not determined when terminal half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%.
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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).
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Assessment of t1/2 for Telotristat Ethyl and LP-778902 (Active Metabolite)
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902.
The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively.
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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).
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Assessment of Apparent Terminal Elimination Rate Constant (λz) for Telotristat Ethyl and LP-778902 (Active Metabolite)
Time Frame: 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).
|
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method.
The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902.
The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively.
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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).
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2016
Primary Completion (Actual)
July 1, 2016
Study Completion (Actual)
July 1, 2016
Study Registration Dates
First Submitted
February 5, 2016
First Submitted That Met QC Criteria
February 11, 2016
First Posted (Estimate)
February 17, 2016
Study Record Updates
Last Update Posted (Actual)
January 25, 2019
Last Update Submitted That Met QC Criteria
January 24, 2019
Last Verified
January 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D-FR-01017-001
- 2015-004120-64 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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