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

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03442725
• Collaborator: (none)
• Enrollment: 16
• Locations: 4
• Arms: 4
• Actual Duration (Months): 3.1
• Patients Per Site: 4
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: Telotristat etiprate	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: Feb 9, 2018
• Actual Primary Completion Date: Apr 27, 2018
• Actual Study Completion Date: May 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Severely decreased renal function group Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).	Drug: Telotristat etiprate; Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.; Other Names: Xermelo®
Active Comparator: Normal renal function group Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).	Drug: Telotristat etiprate; Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.; Other Names: Xermelo®
Experimental: Mildly decreased renal function group Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).	Drug: Telotristat etiprate; Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.; Other Names: Xermelo®
Experimental: Moderately decreased renal function group Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack).	Drug: Telotristat etiprate; Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl.; Other Names: Xermelo®

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

Secondary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.T.C. s.a., Clinical Pharmacology Unit, CHU Sart-Tilman	Liège		Belgium	B-4000
2	CRS Clinical Research Services Kiel GmbH	Kiel		Germany	D-24105
3	ARENSIA Exploratory Medicine Phase I Unit, Republican Clinical Hospital	Chisinau		Moldova, Republic of	MD-2025
4	ARENSIA Unit in Spitalul de Nefrologie	Bucharest		Romania

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 4, 2018
• Study Protocol - Dec 20, 2017

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT03442725
• Other Study ID Numbers: D-FR-01017-002; 2017-003948-20
• First Posted: Feb 22, 2018
• Last Update Posted: Apr 8, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Renal Insufficiency

Study Results

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 Detail	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.

Arm/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	Subjects with normal renal function (estimated glomerular filtration rate [eGFR] ≥90 millilitres/minute/1.73 metres squared [mL/min/1.73 m²]) received a single oral dose of 250 milligrams (mg) telotristat etiprate given under fed conditions (between 15 minutes before and 1 hour after the meal or snack) on Day 1.	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.
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	8	8	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 87.5%	6 75%	13 81.3%
>=65 years	1 12.5%	2 25%	3 18.8%
Sex: Female, Male (Count of Participants)
Female	3 37.5%	3 37.5%	6 37.5%
Male	5 62.5%	5 62.5%	10 62.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	8 100%	16 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Romania	3 37.5%	3 37.5%	6 37.5%
Belgium	1 12.5%	3 37.5%	4 25%
Moldova	2 25%	0 0%	2 12.5%
Germany	2 25%	2 25%	4 25%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of Total Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	Analysis of variance (ANOVA) comparison of Cmax for telotristat ethyl between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.297
	Confidence Interval	(2-Sided) 90%; 0.600 to 2.805
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of Cmax for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.423
	Confidence Interval	(2-Sided) 90%; 0.901 to 2.247
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	1.03	1.00
LP-778902	2.00	2.50
LP-951757	4.00	4.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	Comparison of tmax for telotristat ethyl between test group versus the control group.
	Type of Statistical Test	Other
	Comments	Estimate of the median difference and 90% confidence intervals (CIs) was determined by Hodges-Lehmann estimation.
Statistical Test of Hypothesis	p-Value	0.7452
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 90%; -1.000 to 0.950
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	Comparison of tmax for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments	Estimate of the median difference and 90% CIs was determined by Hodges-Lehmann estimation.
Statistical Test of Hypothesis	p-Value	0.7039
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 90%; -1.000 to 1.000
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	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)

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	1652 (42.7)	2488 (77.9)
LP-951757	876 (66.0)	511 (115)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of AUC0-inf for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.506
	Confidence Interval	(2-Sided) 90%; 0.914 to 2.480
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	1637 (43.3)	2475 (78.3)
LP-951757	845 (64.4)	494 (118)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of AUC0-tlast for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.512
	Confidence Interval	(2-Sided) 90%; 0.915 to 2.498
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	0.0890 (0.0469)	0.0871 (0.0236)
LP-951757	0.0686 (0.0238)	0.0821 (0.0381)

7. Primary Outcome

Title	Apparent Total Clearance From Plasma (CL/F) of Total Telotristat Ethyl
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	1	2
Mean (Standard Deviation) [Litres/hour]	NA (NA)	NA (NA)

8. Primary Outcome

Title	Apparent Volume of Distribution (Vd/F) of Total Telotristat Ethyl
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	1	2
Mean (Standard Deviation) [Litres]	NA (NA)	NA (NA)

9. Primary Outcome

Title	Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	0.115 (0.0589)	0.134 (0.0524)
LP-951757	0.135 (0.295)	0.0608 (0.0923)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of fu of LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Arithmetic Mean Difference
	Estimated Value	0.019
	Confidence Interval	(2-Sided) 90%; -0.030 to 0.068
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Primary Outcome

Title	Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	0.554 (113)	0.957 (70.7)
LP-951757	0.0528 (215)	0.0779 (84.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of Cmaxu for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.727
	Confidence Interval	(2-Sided) 90%; 0.866 to 3.443
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	1.72 (90.3)	3.14 (99.2)
LP-951757	0.955 (237)	1.06 (NA)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of AUC0-infu for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.828
	Confidence Interval	(2-Sided) 90%; 0.903 to 3.699
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Primary Outcome

Title	AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
Telotristat Ethyl	NA (NA)	NA (NA)
LP-778902	1.70 (91.2)	3.12 (99.6)
LP-951757	0.928 (234)	1.05 (NA)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Subjects (Control Group), Severe Renal Impairment (Test Group)
	Comments	ANOVA comparison of AUC0-tlastu for LP-778902 between test group versus the control group.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	1.835
	Confidence Interval	(2-Sided) 90%; 0.904 to 3.726
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Primary Outcome

Title	Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
MRCmax - not normalised	154 (68.9)	204 (143)
MRCmax - normalised	162 (72.4)	215 (151)
MRCmaxTotal - not normalised	0.992 (0.00410)	0.991 (0.00996)
MRCmaxTotal - normalised	0.993 (0.00391)	0.991 (0.00949)

14. Secondary Outcome

Title	Amount of Unchanged Telotristat Ethyl and LP-778902 Excreted in Urine.
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Subjects (Control Group)	Severe Renal Impairment (Test Group)
Arm/Group Description	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.	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.
Measure Participants	8	8
LP-778902: Pre-dose	0 (0)	0 (0)
LP-778902: 0-4 hours post-dose	88966 (50003)	19293 (9447)
LP-778902: 4-8 hours post-dose	152419 (48649)	42976 (22836)
LP-778902: 8-12 hours post-dose	173416 (49499)	47955 (25522)
LP-778902: 12-24 hours post-dose	185970 (47726)	51970 (27925)
LP-778902: 24-48 hours post-dose	191999 (48110)	53997 (29262)
LP-778902: 48-72 hours post-dose	193880 (48123)	54397 (29546)

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).
Arm/Group Title	Healthy Subjects (Control Group)		Severe Renal Impairment (Test Group)
Arm/Group Description	Subjects with normal renal function (eGFR ≥90 mL/min/1.73 m²) received a single 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.		Subjects with severely decreased renal function (eGFR <30 mL/min/1.73 m², not requiring dialysis) received a single 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.
All Cause Mortality
	Healthy Subjects (Control Group)		Severe Renal Impairment (Test Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Healthy Subjects (Control Group)		Severe Renal Impairment (Test Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Subjects (Control Group)		Severe Renal Impairment (Test Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		3/8 (37.5%)
Blood and lymphatic system disorders
Leukocytosis	1/8 (12.5%)	1	0/8 (0%)	0
Gastrointestinal disorders
Nausea	0/8 (0%)	0	1/8 (12.5%)	1
General disorders
Chills	0/8 (0%)	0	1/8 (12.5%)	1
Infections and infestations
Bronchitis	0/8 (0%)	0	1/8 (12.5%)	1
Investigations
C-reactive protein increased	0/8 (0%)	0	1/8 (12.5%)	1
Heart rate increased	0/8 (0%)	0	1/8 (12.5%)	1
Lymphocyte count decreased	0/8 (0%)	0	1/8 (12.5%)	1
Monocyte count increased	0/8 (0%)	0	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/8 (0%)	0	1/8 (12.5%)	1
Muscle spasms	0/8 (0%)	0	1/8 (12.5%)	1
Nervous system disorders
Headache	0/8 (0%)	0	1/8 (12.5%)	2

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.