Renal ImpairmentPhase 1NCT03442725

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

A Phase 1 study testing Telotristat etiprate in people with Renal Impairment, run by Ipsen at 4 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Renal Impairment
What is being tested?: Telotristat etiprate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 4 sitesin 4 countries
Study dates: 9 Feb 2018to 13 May 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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:

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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.

Who cannot join

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).

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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 locations and contacts

4 sites in 4 countries.

Country

City, postcode or hospital

4 sites in 4 countries

Belgium1 site

A.T.C. s.a., Clinical Pharmacology Unit, CHU Sart-Tilman
Liège, B-4000

Other trials in Belgium

Germany1 site

CRS Clinical Research Services Kiel GmbH
Kiel, D-24105

Other trials in Germany

Moldova1 site

ARENSIA Exploratory Medicine Phase I Unit, Republican Clinical Hospital
Chisinau, MD-2025

Other trials in Moldova

Romania1 site

ARENSIA Unit in Spitalul de Nefrologie
Bucharest

Other trials in Romania

About this study

Official title: A Phase I, Open-label Study to Compare the Pharmacokinetics of Telotristat Ethyl and Its Metabolite in Subjects With Impaired Renal Function to Healthy Subjects With Normal Renal Function After a Single Dose of Telotristat Etiprate

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
Being tested: Telotristat etiprate
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03442725
Study group	Role	What they receive
Severely decreased renal function group	Experimental	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). Receives: Drug: Telotristat etiprate
Normal renal function group	Active comparator	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). Receives: Drug: Telotristat etiprate
Mildly decreased renal function group	Experimental	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). Receives: Drug: Telotristat etiprate
Moderately decreased renal function group	Experimental	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). Receives: Drug: Telotristat etiprate

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method with a lower limit of quantitation (LOQ) of 0.5 nanograms (ng)/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757.
Cmax was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757.
Tmax was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757.
T1/2 was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757.
AUC0-inf was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Area Under the Plasma Concentration-Time Curve From Time 0 to Time Corresponding to the Last Quantifiable Concentration (AUC0-tlast) of Total Telotristat Ethyl, LP-778902 and LP-951757
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757.
AUC0-tlast was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757.
λz was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Apparent Total Clearance From Plasma (CL/F) of Total Telotristat Ethyl
Blood samples were collected to determine plasma levels of telotristat ethyl using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL.
CL/F was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Apparent Volume of Distribution (Vd/F) of Total Telotristat Ethyl
Blood samples were collected to determine plasma levels of telotristat ethyl using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL.
Vd/F was determined using non-compartmental analysis.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757
Plasma protein binding was assessed using equilibrium dialysis followed by LC-MS/MS for determination of unbound drug concentrations. The plasma protein binding of telotristat ethyl, LP-778902 and LP-951757 was assessed and the percentage of fu was calculated as the mean over time of the mean of the available replicates.
Measured: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Cmaxu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis.
Measured: Day 1 (0.5, 1, 2 and 3 hours post-dose)
AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
AUC0-infu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis.
Measured: Day 1 (0.5, 1, 2 and 3 hours post-dose)
AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
AUC0-tlastu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis.
Measured: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl)
The following MRs of Cmax were calculated:
MRCmax = (Cmax LP-778902)/(Cmax telotristat ethyl)
MRCmaxTotal = (Cmax LP-778902)/(Cmax LP-778902+Cmax telotristat ethyl)
The ratios were also normalised by molecular weight (MW) of the metabolites (telotristat ethyl: MW=575 grams/mole (g/mol) and LP-778902: MW=547 g/mol). Both the normalised and not normalised ratios are presented.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)

Secondary outcomes (1)

Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine.
For assessment of urine PK parameters, the amount of unchanged telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) excreted in urine was determined.
Measured: Day 1 (predose and 0 to 4 hours, 4 to 8 hours, 8 to 12 hours, 12 to 24 hours post-dose), Day 2 (24 to 48 hours post-dose), Day 3 (48 to 72 hours post-dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Feb 201813 May 2018

First posted22 Feb 2018
Study start9 Feb 2018
Primary completion27 Apr 2018
Study completion13 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by IpsenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03442725
Sponsor's protocol ID: D-FR-01017-002
Other IDs: 2017-003948-20, 2017
Status last verified: Mar 2020
First submitted: 26 Jan 2018
Last updated: 8 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-label Study to Compare the Pharmacokinetics of Telotristat Ethyl and Its Metabolite in Subjects With Impaired Renal Function to Healthy Subjects With Normal Renal Function After a Single Dose of Telotristat Etiprate
ClinicalTrials.gov ID: NCT03442725
Acronym / sponsor ID: D-FR-01017-002
Conditions: Renal Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: IpsenIndustry (pharma, biotech, devices)
Study start: 9 Feb 2018 (actual)
Primary completion: 27 Apr 2018 (actual)
Study completion: 13 May 2018 (actual)
First posted: 22 Feb 2018 (actual)
Results: Posted 13 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Severely decreased renal function group	Experimental	Drug: Telotristat etiprateSubjects 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).
Normal renal function group	Active comparator	Drug: Telotristat etiprateSubjects 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).
Mildly decreased renal function group	Experimental	Drug: Telotristat etiprateSubjects 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).
Moderately decreased renal function group	Experimental	Drug: Telotristat etiprateSubjects 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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.
Clinical diagnosis of renal impaired function that has been stable for more than 3 months prior to dosing

Key exclusion criteria (22 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Telotristat etiprateAlso: Xermelo®Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.	Drug	Mildly decreased renal function group, Moderately decreased renal function group, Normal renal function group, Severely decreased renal function group

Primary outcome

Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method with a lower limit of quantitation (LOQ) of 0.5 nanograms (ng)/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. Cmax was determined using non-compartmental analysis.
Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. Tmax was determined using non-compartmental analysis.
Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. T1/2 was determined using non-compartmental analysis.
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. AUC0-inf was determined using non-compartmental analysis.
Area Under the Plasma Concentration-Time Curve From Time 0 to Time Corresponding to the Last Quantifiable Concentration (AUC0-tlast) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. AUC0-tlast was determined using non-compartmental analysis.
Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. λz was determined using non-compartmental analysis.
Apparent Total Clearance From Plasma (CL/F) of Total Telotristat Ethyl
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL. CL/F was determined using non-compartmental analysis.
Apparent Volume of Distribution (Vd/F) of Total Telotristat Ethyl
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Blood samples were collected to determine plasma levels of telotristat ethyl using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL. Vd/F was determined using non-compartmental analysis.
Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Plasma protein binding was assessed using equilibrium dialysis followed by LC-MS/MS for determination of unbound drug concentrations. The plasma protein binding of telotristat ethyl, LP-778902 and LP-951757 was assessed and the percentage of fu was calculated as the mean over time of the mean of the available replicates.
Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Cmaxu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis.
AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
AUC0-infu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis.
AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
AUC0-tlastu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis.
Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl)
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
The following MRs of Cmax were calculated: MRCmax = (Cmax LP-778902)/(Cmax telotristat ethyl) MRCmaxTotal = (Cmax LP-778902)/(Cmax LP-778902+Cmax telotristat ethyl) The ratios were also normalised by molecular weight (MW) of the metabolites (telotristat ethyl: MW=575 grams/mole (g/mol) and LP-778902: MW=547 g/mol). Both the normalised and not normalised ratios are presented.

1 secondary outcome

Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine.
Time frame: Day 1 (predose and 0 to 4 hours, 4 to 8 hours, 8 to 12 hours, 12 to 24 hours post-dose), Day 2 (24 to 48 hours post-dose), Day 3 (48 to 72 hours post-dose)

Results and safety

Results posted to the registry on 13 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Subjects (Control Group)	8	8
Severe Renal Impairment (Test Group)	8	8

Primary outcome: Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757

Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours). Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Healthy Subjects (Control Group) n = 8	Severe Renal Impairment (Test Group) n = 8
Telotristat Ethyl	3.81 (98.9)	4.94 (116)
LP-778902	533 (58.1)	759 (52.9)
LP-951757	65.2 (46.0)	45.6 (80.2)

Healthy Subjects (Control Group) vs Severe Renal Impairment (Test Group): Geometric Mean Ratio: 1.297 (90% CI 0.600 to 2.805)
Healthy Subjects (Control Group) vs Severe Renal Impairment (Test Group): Geometric Mean Ratio: 1.423 (90% CI 0.901 to 2.247)

Population analysed: The pharmacokinetic (PK) population included all subjects who received the single oral dose of study drug and had no major protocol deviations affecting the PK variables and for whom the renal function group was assessable and who had a sufficient number of plasma concentrations to estimate the main PK parameters.

Primary outcome: Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757

Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours). Median (Full Range). Unit: hours

Measure	Healthy Subjects (Control Group) n = 8	Severe Renal Impairment (Test Group) n = 8
Telotristat Ethyl	1.03 (0.500 to 3.00)	1.00 (0.500 to 3.00)
LP-778902	2.00 (1.00 to 4.00)	2.50 (1.00 to 3.00)
LP-951757	4.00 (3.00 to 8.00)	4.00 (2.02 to 6.00)

Healthy Subjects (Control Group) vs Severe Renal Impairment (Test Group): Median Difference: 0.000 (90% CI -1.000 to 0.950), p = 0.7452, Wilcoxon (Mann-Whitney)
Healthy Subjects (Control Group) vs Severe Renal Impairment (Test Group): Median Difference: 0.000 (90% CI -1.000 to 1.000), p = 0.7039, Wilcoxon (Mann-Whitney)

Population analysed: The PK population included all subjects who received the single oral dose of study drug and had no major protocol deviations affecting the PK variables and for whom the renal function group was assessable and who had a sufficient number of plasma concentrations to estimate the main PK parameters.

Primary outcome: Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757

Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours). Mean (Standard Deviation). Unit: hours

Measure	Healthy Subjects (Control Group) n = 8	Severe Renal Impairment (Test Group) n = 8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	9.05 (3.02)	8.31 (1.51)
LP-951757	11.5 (4.65)	9.93 (4.45)

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757

Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours). Geometric mean (Geometric Coefficient of Variation). Unit: ng*hour/mL

Measure	Healthy Subjects (Control Group) n = 8	Severe Renal Impairment (Test Group) n = 8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	1652 (42.7)	2488 (77.9)
LP-951757	876 (66.0)	511 (115)

Healthy Subjects (Control Group) vs Severe Renal Impairment (Test Group): Geometric Mean Ratio: 1.506 (90% CI 0.914 to 2.480)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Treatment emergent adverse events were recorded from Day 1 to the end of study visit between Day 8 and Day 15 (overall timeframe: up to 15 days).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Healthy Subjects (Control Group)	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Severe Renal Impairment (Test Group)	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8

Limitations and caveats (from the sponsor): In accordance with the statistical analysis plan, PK parameters were not calculated if more than one-third of the values were BLQ at a single time point. No statistical comparisons were performed on PK parameters for LP-951757.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ipsen Medical Director study director

Ipsen

4 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Telotristat etiprate in people with Renal Impairment, run by Ipsen at 4 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Belgium, Germany, Moldova, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 (time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03442725.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2020.