Renal Impairment
Conditions
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.
Interventions
Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.
Sponsors
Ipsen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | 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. |
| Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | 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) | 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. |
Countries
Belgium, Germany, Moldova, Romania
Participant flow
Recruitment details
A total of 16 subjects were recruited in this open label, single dose study between February and May 2018. Recruited subjects were split evenly between 2 groups (control group and test group).
Pre-assignment details
The control group comprised 8 healthy subjects with normal renal function and who were demographically matched to test group by age (±10 years), sex and body mass index (BMI) (±20%). 8 subjects with severely impaired renal function but not requiring dialysis were recruited into the test group.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Subjects (Control Group) Subjects with normal renal function (eGFR ≥90 mL/min/1.73 m²) received a single oral dose of 250 mg telotristat etiprate given under fed conditions (between 15 minutes before and 1 hour after the meal or snack) on Day 1. | 8 |
| Severe Renal Impairment (Test Group) Subjects with severely decreased renal function (eGFR \<30 mL/min/1.73 m², not requiring dialysis) received a single oral dose of 250 mg telotristat etiprate given under fed conditions (between 15 minutes before and 1 hour after the meal or snack) on Day 1. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Healthy Subjects (Control Group) | Severe Renal Impairment (Test Group) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 16 Participants |
| Region of Enrollment Belgium | 1 participants | 3 participants | 4 participants |
| Region of Enrollment Germany | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Moldova | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Romania | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA hour^-1 | — |
| Healthy Subjects (Control Group) | Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 0.0890 hour^-1 | Standard Deviation 0.0469 |
| Healthy Subjects (Control Group) | Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.0686 hour^-1 | Standard Deviation 0.0238 |
| Severe Renal Impairment (Test Group) | Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA hour^-1 | — |
| Severe Renal Impairment (Test Group) | Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 0.0871 hour^-1 | Standard Deviation 0.0236 |
| Severe Renal Impairment (Test Group) | Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.0821 hour^-1 | Standard Deviation 0.0381 |
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA hours | — |
| Healthy Subjects (Control Group) | Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 9.05 hours | Standard Deviation 3.02 |
| Healthy Subjects (Control Group) | Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 11.5 hours | Standard Deviation 4.65 |
| Severe Renal Impairment (Test Group) | Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA hours | — |
| Severe Renal Impairment (Test Group) | Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 8.31 hours | Standard Deviation 1.51 |
| Severe Renal Impairment (Test Group) | Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 9.93 hours | Standard Deviation 4.45 |
Primary
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.
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)
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Healthy Subjects (Control Group) | Apparent Total Clearance From Plasma (CL/F) of Total Telotristat Ethyl | NA Litres/hour |
| Severe Renal Impairment (Test Group) | Apparent Total Clearance From Plasma (CL/F) of Total Telotristat Ethyl | NA Litres/hour |
Primary
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.
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)
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Healthy Subjects (Control Group) | Apparent Volume of Distribution (Vd/F) of Total Telotristat Ethyl | NA Litres |
| Severe Renal Impairment (Test Group) | Apparent Volume of Distribution (Vd/F) of Total Telotristat Ethyl | NA Litres |
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng*hour/mL | — |
| Healthy Subjects (Control Group) | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 1652 ng*hour/mL | Geometric Coefficient of Variation 42.7 |
| Healthy Subjects (Control Group) | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 876 ng*hour/mL | Geometric Coefficient of Variation 66 |
| Severe Renal Impairment (Test Group) | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng*hour/mL | — |
| Severe Renal Impairment (Test Group) | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 2488 ng*hour/mL | Geometric Coefficient of Variation 77.9 |
| Severe Renal Impairment (Test Group) | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 511 ng*hour/mL | Geometric Coefficient of Variation 115 |
Comparison: ANOVA comparison of AUC0-inf for LP-778902 between test group versus the control group.90% CI: [0.914, 2.48]
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | 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 | LP-951757 | 845 ng*hour/mL | Geometric Coefficient of Variation 64.4 |
| Healthy Subjects (Control Group) | 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 | Telotristat Ethyl | NA ng*hour/mL | — |
| Healthy Subjects (Control Group) | 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 | LP-778902 | 1637 ng*hour/mL | Geometric Coefficient of Variation 43.3 |
| Severe Renal Impairment (Test Group) | 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 | LP-778902 | 2475 ng*hour/mL | Geometric Coefficient of Variation 78.3 |
| Severe Renal Impairment (Test Group) | 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 | LP-951757 | 494 ng*hour/mL | Geometric Coefficient of Variation 118 |
| Severe Renal Impairment (Test Group) | 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 | Telotristat Ethyl | NA ng*hour/mL | — |
Comparison: ANOVA comparison of AUC0-tlast for LP-778902 between test group versus the control group.90% CI: [0.915, 2.498]
Primary
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.
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng*hour/mL | — |
| Healthy Subjects (Control Group) | AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 1.72 ng*hour/mL | Geometric Coefficient of Variation 90.3 |
| Healthy Subjects (Control Group) | AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.955 ng*hour/mL | Geometric Coefficient of Variation 237 |
| Severe Renal Impairment (Test Group) | AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng*hour/mL | — |
| Severe Renal Impairment (Test Group) | AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 3.14 ng*hour/mL | Geometric Coefficient of Variation 99.2 |
| Severe Renal Impairment (Test Group) | AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 1.06 ng*hour/mL | — |
Comparison: ANOVA comparison of AUC0-infu for LP-778902 between test group versus the control group.90% CI: [0.903, 3.699]
Primary
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.
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng*hour/mL | — |
| Healthy Subjects (Control Group) | AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 1.70 ng*hour/mL | Geometric Coefficient of Variation 91.2 |
| Healthy Subjects (Control Group) | AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.928 ng*hour/mL | Geometric Coefficient of Variation 234 |
| Severe Renal Impairment (Test Group) | AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng*hour/mL | — |
| Severe Renal Impairment (Test Group) | AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 3.12 ng*hour/mL | Geometric Coefficient of Variation 99.6 |
| Severe Renal Impairment (Test Group) | AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 1.05 ng*hour/mL | — |
Comparison: ANOVA comparison of AUC0-tlastu for LP-778902 between test group versus the control group.90% CI: [0.904, 3.726]
Primary
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.
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng/mL | — |
| Healthy Subjects (Control Group) | Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 0.554 ng/mL | Geometric Coefficient of Variation 113 |
| Healthy Subjects (Control Group) | Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.0528 ng/mL | Geometric Coefficient of Variation 215 |
| Severe Renal Impairment (Test Group) | Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA ng/mL | — |
| Severe Renal Impairment (Test Group) | Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 0.957 ng/mL | Geometric Coefficient of Variation 70.7 |
| Severe Renal Impairment (Test Group) | Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.0779 ng/mL | Geometric Coefficient of Variation 84 |
Comparison: ANOVA comparison of Cmaxu for LP-778902 between test group versus the control group.90% CI: [0.866, 3.443]
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | 3.81 ng/mL | Geometric Coefficient of Variation 98.9 |
| Healthy Subjects (Control Group) | Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 533 ng/mL | Geometric Coefficient of Variation 58.1 |
| Healthy Subjects (Control Group) | Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 65.2 ng/mL | Geometric Coefficient of Variation 46 |
| Severe Renal Impairment (Test Group) | Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | 4.94 ng/mL | Geometric Coefficient of Variation 116 |
| Severe Renal Impairment (Test Group) | Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 759 ng/mL | Geometric Coefficient of Variation 52.9 |
| Severe Renal Impairment (Test Group) | Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 45.6 ng/mL | Geometric Coefficient of Variation 80.2 |
Comparison: Analysis of variance (ANOVA) comparison of Cmax for telotristat ethyl between test group versus the control group.90% CI: [0.6, 2.805]
Comparison: ANOVA comparison of Cmax for LP-778902 between test group versus the control group.90% CI: [0.901, 2.247]
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmax - not normalised | 154 Ratio | Standard Deviation 68.9 |
| Healthy Subjects (Control Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmax - normalised | 162 Ratio | Standard Deviation 72.4 |
| Healthy Subjects (Control Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmaxTotal - not normalised | 0.992 Ratio | Standard Deviation 0.0041 |
| Healthy Subjects (Control Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmaxTotal - normalised | 0.993 Ratio | Standard Deviation 0.00391 |
| Severe Renal Impairment (Test Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmaxTotal - normalised | 0.991 Ratio | Standard Deviation 0.00949 |
| Severe Renal Impairment (Test Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmax - not normalised | 204 Ratio | Standard Deviation 143 |
| Severe Renal Impairment (Test Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmaxTotal - not normalised | 0.991 Ratio | Standard Deviation 0.00996 |
| Severe Renal Impairment (Test Group) | Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | MRCmax - normalised | 215 Ratio | Standard Deviation 151 |
Primary
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.
Time frame: Day 1 (0.5, 1, 2 and 3 hours post-dose)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA Percentage of fu | — |
| Healthy Subjects (Control Group) | Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 0.115 Percentage of fu | Standard Deviation 0.0589 |
| Healthy Subjects (Control Group) | Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.135 Percentage of fu | Standard Deviation 0.295 |
| Severe Renal Impairment (Test Group) | Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | NA Percentage of fu | — |
| Severe Renal Impairment (Test Group) | Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 0.134 Percentage of fu | Standard Deviation 0.0524 |
| Severe Renal Impairment (Test Group) | Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 0.0608 Percentage of fu | Standard Deviation 0.0923 |
Comparison: ANOVA comparison of fu of LP-778902 between test group versus the control group.90% CI: [-0.03, 0.068]
Primary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Subjects (Control Group) | Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | 1.03 hours |
| Healthy Subjects (Control Group) | Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 2.00 hours |
| Healthy Subjects (Control Group) | Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 4.00 hours |
| Severe Renal Impairment (Test Group) | Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Telotristat Ethyl | 1.00 hours |
| Severe Renal Impairment (Test Group) | Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-778902 | 2.50 hours |
| Severe Renal Impairment (Test Group) | Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | LP-951757 | 4.00 hours |
Comparison: Comparison of tmax for telotristat ethyl between test group versus the control group.p-value: 0.745290% CI: [-1, 0.95]Wilcoxon (Mann-Whitney)
Comparison: Comparison of tmax for LP-778902 between test group versus the control group.p-value: 0.703990% CI: [-1, 1]Wilcoxon (Mann-Whitney)
Secondary
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 4-8 hours post-dose | 152419 ng | Standard Deviation 48649 |
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 24-48 hours post-dose | 191999 ng | Standard Deviation 48110 |
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 8-12 hours post-dose | 173416 ng | Standard Deviation 49499 |
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 0-4 hours post-dose | 88966 ng | Standard Deviation 50003 |
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 12-24 hours post-dose | 185970 ng | Standard Deviation 47726 |
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: Pre-dose | 0 ng | Standard Deviation 0 |
| Healthy Subjects (Control Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 48-72 hours post-dose | 193880 ng | Standard Deviation 48123 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 48-72 hours post-dose | 54397 ng | Standard Deviation 29546 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 24-48 hours post-dose | 53997 ng | Standard Deviation 29262 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: Pre-dose | 0 ng | Standard Deviation 0 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 0-4 hours post-dose | 19293 ng | Standard Deviation 9447 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 4-8 hours post-dose | 42976 ng | Standard Deviation 22836 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 8-12 hours post-dose | 47955 ng | Standard Deviation 25522 |
| Severe Renal Impairment (Test Group) | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | LP-778902: 12-24 hours post-dose | 51970 ng | Standard Deviation 27925 |
| Unknown | Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine. | Telotristat Ethyl: All timepoints | — ng | — |