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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004120-64 | EudraCT Number |
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The purpose of the protocol is to assess the pharmacokinetics, safety and tolerability of a single dose of telotristat etiprate in subjects with various stages of hepatic impairment compared to healthy control subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Telotristat etiprate 500 mg | Experimental | 1 single oral dose (2 x 250-mg tablets) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| telotristat etiprate | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Maximum Observed Plasma Drug Concentration (Cmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining pharmacokinetic (PK) parameters for total telotristat ethyl using a validated, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 nanograms per millilitre (ng/mL) for telotristat ethyl and the lower limit of quantification (LoQ) was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours [h] post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of Time to Maximum Observed Plasma Concentration (Tmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of Area Under the Plasma Concentration Time Curve From 0 to Time t Corresponding to the Last Quantifiable Concentration (AUC[0-tlast]) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ARENSIA Exploratory Medicine | Chisinau | MD-2025 | Moldova | |||
| ARENSIA Exploratory Medicine |
Subjects enrolled into 3 hepatic functional groups:
C-P score was summed from 5 clinical assessments of liver disease; each measure scored 1-3, with 3 indicating most severe derangement.
This was an open-label study conducted at 2 investigational sites, one in Romania and one in the Republic of Moldova. Subjects were enrolled to the study from 08 February 2016 (first subject enrolled) until 07 July 2016 (last subject completed).
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Control | Subjects in the healthy control group were assessed as having normal hepatic function. All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| FG001 | Mild HI | Subjects in the mild HI group were assessed as C-P class A (5 to 6 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| FG002 | Moderate HI | Subjects in the moderate HI group were assessed as C-P class B (7 to 9 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Baseline characteristics are reported for the safety population which corresponds to all subjects who received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Control | Subjects in the healthy control group were assessed as having normal hepatic function. All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| BG001 | Mild HI |
| 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 | Assessment of Maximum Observed Plasma Drug Concentration (Cmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining pharmacokinetic (PK) parameters for total telotristat ethyl using a validated, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 nanograms per millilitre (ng/mL) for telotristat ethyl and the lower limit of quantification (LoQ) was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | The PK population (23 subjects overall) corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours [h] post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
Up to 15 days (Day 1 to Day 15)
Adverse event (AE) data is reported for the safety population which corresponds to all subjects who received at least one dose of study medication (24 subjects overall). Data is reported as treatment-emergent AEs, defined as any AE occurring during the active phase of the study until the end of study or early discontinuation visit.
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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 Control | Subjects in the healthy control group were assessed as having normal hepatic function. All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
No safety risks were identified in mild or moderate HI subjects but due to uncertainties regarding potential exposure of study medication in severe HI subjects, it was decided not to enrol any subjects with severe HI (optional as per the protocol).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Ipsen Pharma | clinical.trials@ipsen.com |
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| ID | Term |
|---|---|
| C000592493 | telotristat |
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| Assessment of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC[0-inf]) for Telotristat Ethyl | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. AUC(0-inf) was not determined when the apparent terminal elimination half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of Cmax for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of Tmax for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group and Comparison Between Each Hepatic Impairment Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of AUC(0-tlast) for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of AUC(0-inf) for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. AUC(0-inf) was not determined when terminal half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of t1/2 for Telotristat Ethyl and LP-778902 (Active Metabolite) | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902. The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Assessment of Apparent Terminal Elimination Rate Constant (λz) for Telotristat Ethyl and LP-778902 (Active Metabolite) | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902. The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively. | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
| Bucharest |
| 050159 Distr |
| Romania |
Subjects in the mild HI group were assessed as C-P class A (5 to 6 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| BG002 | Moderate HI | Subjects in the moderate HI group were assessed as C-P class B (7 to 9 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| BG003 | Total Title |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Healthy Control | Subjects in the healthy control group were assessed as having normal hepatic function. All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| OG001 | Mild HI | Subjects in the mild HI group were assessed as C-P class A (5 to 6 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| OG002 | Moderate HI | Subjects in the moderate HI group were assessed as C-P class B (7 to 9 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
| OG003 | All HI | The all HI group represented all subjects in either HI group (mild + moderate). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. |
|
|
|
| Primary | Assessment of Time to Maximum Observed Plasma Concentration (Tmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). | Posted | Median | Full Range | hour | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
|
|
|
| Primary | Assessment of Area Under the Plasma Concentration Time Curve From 0 to Time t Corresponding to the Last Quantifiable Concentration (AUC[0-tlast]) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
|
|
|
| Primary | Assessment of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC[0-inf]) for Telotristat Ethyl | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. AUC(0-inf) was not determined when the apparent terminal elimination half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). Only subjects with data available for analysis are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
|
|
| Primary | Assessment of Cmax for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
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|
|
| Primary | Assessment of Tmax for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group and Comparison Between Each Hepatic Impairment Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). | Posted | Median | Full Range | hour | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
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|
|
| Primary | Assessment of AUC(0-tlast) for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
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|
|
| Primary | Assessment of AUC(0-inf) for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group | Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. AUC(0-inf) was not determined when terminal half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). Only subjects with data available for analysis are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
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| Primary | Assessment of t1/2 for Telotristat Ethyl and LP-778902 (Active Metabolite) | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902. The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). Only subjects with data available for analysis are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
|
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| Primary | Assessment of Apparent Terminal Elimination Rate Constant (λz) for Telotristat Ethyl and LP-778902 (Active Metabolite) | Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902. The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively. | The PK population corresponded to all subjects who received at least one dose of study medication, without protocol violation affecting PK evaluation and who had a sufficient number of plasma concentrations to estimate the main PK parameters (Cmax, Tmax and AUC[0-tlast]). Only subjects with data available for analysis are reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour^-1 | Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h). |
|
|
|
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | Mild HI | Subjects in the mild HI group were assessed as C-P class A (5 to 6 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. | 0 | 8 | 2 | 8 |
| EG002 | Moderate HI | Subjects in the moderate HI group were assessed as C-P class B (7 to 9 points on C-P scale for classification of the severity of liver disease). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. | 0 | 8 | 3 | 8 |
| EG003 | All HI | The all HI group represented all subjects in either HI group (mild + moderate). All subjects in each study group received a single oral dose of telotristat ethyl hippurate 500 mg (2x250 mg) on Day 1. | 0 | 16 | 5 | 16 |
| Abdominal pain | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA19.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA19.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA19.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA19.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA19.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA19.0 | Systematic Assessment |
|
The PI will provide the sponsor with any results communications for public release at least 90 days prior to the planned submission for their review.
The Tmax was analysed using a non-parametric analysis (Walsh averages and appropriate quantile of the Wilcoxon signed rank test statistic). The median difference between the moderate HI group (Test) versus healthy control group (Reference) and the corresponding 90% CIs were calculated by Hodges-Lehmann estimation. |
| Wilcoxon (Mann-Whitney) |
| =1.0000 |
| Median difference |
| 0.000 |
| 2-Sided |
| 90 |
| 0.000 |
| 0.000 |
| Superiority or Other |
| Comparison of moderate HI group (Test) versus healthy control group (Reference) on AUC(0-tlast) values for telotristat ethyl. | Geometric LS mean ratio | 3.168 | 2-Sided | 90 | 1.715 | 5.852 | A repeated-measures ANOVA was performed using a linear mixed effects model, with hepatic function group as a fixed term. Geometric LS mean ratios were derived for each HI group (Test) versus healthy control group (Reference). | Superiority or Other |
|
Comparison of moderate HI group (Test) versus healthy control group (Reference) on Cmax values for LP-778902. |
| Geometric LS mean ratio |
| 2.00 |
| 2-Sided |
| 90 |
| 1.51 |
| 2.66 |
A repeated-measures ANOVA was performed using a linear mixed effects model, with hepatic function group as a fixed term. Geometric LS mean ratios were derived for each HI group (Test) versus healthy control group (Reference). |
| Superiority or Other |
The Tmax was analysed using a non-parametric analysis (Walsh averages and appropriate quantile of the Wilcoxon signed rank test statistic). The median differences between the hepatic impaired group (Test) versus the healthy control group (Reference) and the corresponding 90% CIs were calculated by Hodges-Lehmann estimation. |
| Wilcoxon (Mann-Whitney) |
| =0.4671 |
| Median difference |
| 0.000 |
| 2-Sided |
| 90 |
| 0.000 |
| 1.000 |
| Superiority or Other |
|
Comparison of moderate HI group (Test) versus healthy control group (Reference) on AUC(0-tlast) values for LP-778902. |
| Geometric LS mean ratio |
| 3.52 |
| 2-Sided |
| 90 |
| 2.45 |
| 5.03 |
A repeated-measures ANOVA was performed using a linear mixed effects model, with hepatic function group as a fixed term. Geometric LS mean ratios were derived for each HI group (Test) versus healthy control group (Reference). |
| Superiority or Other |
| Comparison of moderate HI group (Test) versus healthy control group (Reference) on AUC(0-inf) values for LP-778902. | Geometric LS mean ratio | 3.32 | 2-Sided | 90 | 2.30 | 4.80 | A repeated-measures ANOVA was performed using a linear mixed effects model, with hepatic function group as a fixed term. Geometric LS mean ratios were derived for each HI group (Test) versus healthy control group (Reference). | Superiority or Other |
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| LP-778902 |
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| LP-778902 |
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