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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003948-20 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Severely decreased renal function group | Experimental | Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack). |
|
| Normal renal function group | Active Comparator | Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack). |
|
| Mildly decreased renal function group | Experimental | Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack). |
|
| Moderately decreased renal function group | Experimental | Subjects will receive a single oral 250-mg tablet dose of Telotristat etiprate (Xermelo® 250 mg) on day 1 under fed conditions (i.e. between 15 minutes before and 1 hour after the meal or snack). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Telotristat etiprate | Drug | Oral administration of 1 tablet of Xermelo® containing telotristat etiprate equivalent to 250 mg telotristat ethyl. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Time to Maximum Observed Plasma Concentration (Tmax) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. Tmax was determined using non-compartmental analysis. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Apparent Terminal Elimination Half-Life (t1/2) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. T1/2 was determined using non-compartmental analysis. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Total Telotristat Ethyl, LP-778902 and LP-951757 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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) |
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Inclusion Criteria:
All subjects:
Additionally, for subjects with renal impaired function:
Additionally, for healthy subjects with normal renal function:
Exclusion Criteria:
All subjects:
Additionally, for renal impaired subjects:
Additionally, for healthy subjects with normal renal function:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| A.T.C. s.a., Clinical Pharmacology Unit, CHU Sart-Tilman | Liège | B-4000 | Belgium | |||
| CRS Clinical Research Services Kiel GmbH |
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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Subjects (Control Group) | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Severe Renal Impairment (Test Group) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
|
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Subjects (Control Group) | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| C-reactive protein increased | Investigations | MedDra (20.0) | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen | See email | clinical.trials@ipsen.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 4, 2018 | Mar 7, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Dec 20, 2017 | Mar 7, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C000592493 | telotristat |
| C000621725 | telotristat ethyl |
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|
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.
| Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Time Corresponding to the Last Quantifiable Concentration (AUC0-tlast) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. AUC0-tlast was determined using non-compartmental analysis. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Apparent First Order Terminal Elimination Rate Constant (λz) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Blood samples were collected to determine plasma levels of telotristat ethyl, its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL for telotristat ethyl and 2 ng/mL for LP-778902 and LP-951757. λz was determined using non-compartmental analysis. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Apparent Total Clearance From Plasma (CL/F) of Total Telotristat Ethyl | Blood samples were collected to determine plasma levels of telotristat ethyl using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL. CL/F was determined using non-compartmental analysis. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Apparent Volume of Distribution (Vd/F) of Total Telotristat Ethyl | Blood samples were collected to determine plasma levels of telotristat ethyl using a validated, specific and sensitive LC-MS/MS bioanalytical method with a LOQ of 0.5 ng/mL. Vd/F was determined using non-compartmental analysis. | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours) |
| Percentage of Unbound Plasma Fraction (fu) of Total Telotristat Ethyl, LP-778902 and LP-951757 | Plasma protein binding was assessed using equilibrium dialysis followed by LC-MS/MS for determination of unbound drug concentrations. The plasma protein binding of telotristat ethyl, LP-778902 and LP-951757 was assessed and the percentage of fu was calculated as the mean over time of the mean of the available replicates. | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
| Cmax for the Unbound Fraction (Cmaxu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | Cmaxu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis. | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
| AUC0-inf for the Unbound Fraction (AUC0-infu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | AUC0-infu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis. | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
| AUC0-tlast for the Unbound Fraction (AUC0-tlastu) of Unbound Telotristat Ethyl, LP-778902 and LP-951757 | AUC0-tlastu of unbound telotristat ethyl and its active metabolite LP-778902 (also known as telotristat) and the inactive metabolite LP-951757 was calculated using the unbound fraction fu (defined for each subject as the mean over all time points of the mean of fu) and determined using non-compartmental analysis. | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
| Metabolic Ratios (MR) of Cmax (LP-778902/Telotristat Ethyl) | The following MRs of Cmax were calculated: MRCmax = (Cmax LP-778902)/(Cmax telotristat ethyl) MRCmaxTotal = (Cmax LP-778902)/(Cmax LP-778902+Cmax telotristat ethyl) The ratios were also normalised by molecular weight (MW) of the metabolites (telotristat ethyl: MW=575 grams/mole (g/mol) and LP-778902: MW=547 g/mol). Both the normalised and not normalised ratios are presented. | 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) |
| Kiel |
| D-24105 |
| Germany |
| ARENSIA Exploratory Medicine Phase I Unit, Republican Clinical Hospital | Chisinau | MD-2025 | Moldova |
| ARENSIA Unit in Spitalul de Nefrologie | Bucharest | Romania |
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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 |
| 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. |
| OG001 | 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. |
|
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| 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. | 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. | Posted | Median | Full Range | hours | 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) |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | hours | 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) |
|
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|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hour/mL | 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) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hour/mL | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | hour^-1 | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Litres/hour | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Litres | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Percentage of fu | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hour/mL | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hour/mL | Day 1 (0.5, 1, 2 and 3 hours post-dose) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Ratio | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng | 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) |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 1 |
| 8 |
| EG001 | Severe Renal Impairment (Test Group) | 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. | 0 | 8 | 0 | 8 | 3 | 8 |
| Heart rate increased | Investigations | MedDra (20.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDra (20.0) | Systematic Assessment |
|
| Monocyte count increased | Investigations | MedDra (20.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDra (20.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDra (20.0) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDra (20.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDra (20.0) | Systematic Assessment |
|
| Chills | General disorders | MedDra (20.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDra (20.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDra (20.0) | Systematic Assessment |
|
Not provided
Not provided
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| LP-951757 |
|
Comparison of tmax for LP-778902 between test group versus the control group. |
| Wilcoxon (Mann-Whitney) |
| 0.7039 |
| Median Difference |
| 0.000 |
| 2-Sided |
| 90 |
| -1.000 |
| 1.000 |
| Other |
Estimate of the median difference and 90% CIs was determined by Hodges-Lehmann estimation. |
| LP-778902 |
|
|
| LP-951757 |
|
|
| LP-778902 |
|
|
| LP-951757 |
|
|
| LP-778902 |
|
|
| LP-951757 |
|
|
| LP-778902 |
|
|
| LP-951757 |
|
|
| LP-951757 |
|
| LP-951757 |
|
| LP-778902 |
|
|
| LP-951757 |
|
|
| LP-778902 |
|
|
| LP-951757 |
|
|
| MRCmaxTotal - not normalised |
|
| MRCmaxTotal - normalised |
|
|
| LP-778902: 0-4 hours post-dose |
|
|
| LP-778902: 4-8 hours post-dose |
|
|
| LP-778902: 8-12 hours post-dose |
|
|
| LP-778902: 12-24 hours post-dose |
|
|
| LP-778902: 24-48 hours post-dose |
|
|
| LP-778902: 48-72 hours post-dose |
|
|