Healthy Volunteer
Conditions
Brief summary
This open-label study will assess the effects of hepatic impairment on the pharmacokinetics of a single oral dose of aleglitazar in subjects with mild or moderate hepatic impairment (Child-Pugh class A or B) and in matched control subjects with normal hepatic function. Subjects will receive a single oral dose of aleglitazar, with assessment of the pharmacokinetics of aleglitazar on Days 1-5. Anticipated duration of study for each enrolled subject is approximately 6 weeks.
Interventions
DRUGaleglitazar
single oral dose
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female adults, 18-70 years of age inclusive * Normal hepatic function or mild to moderate impaired liver function (Child-Pugh class A or B) * Body mass index (BMI) 18 to 40 kg/m2 inclusive * Females must be either surgically sterile, postmenopausal, or willing to use two reliable methods of contraception for the duration of the study and started 3 months before study start
Exclusion criteria
* For subjects with hepatic impairment: evidence of progressive liver disease within the last 4 weeks, or biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder and/or disease * For healthy volunteers: positive test for hepatitis B or C, alcohol intake of more than 14 units per week, or history of clinically significant alcohol or drug abuse * Acute infection or current malignancy requiring treatment * History of clinically significant allergic disease or drug hypersensitivity * Positive test for HIV-1 or HIV-2 at screening * Participation in a clinical study with an investigational drug or new chemical entity within 2 months prior to screening * Females who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | AUCinf was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. |
| Maximum Plasma Concentration (Cmax) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | Cmax was obtained directly from the concentration-time data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of M1 and M6 | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | M1 and M6 are pharmacologically inactive metabolites of aleglitazar. Cmax was obtained directly from the concentration-time data. |
| Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | AUClast was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. |
| Apparent Total Body Clearance (CL/F) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. |
| Renal Clearance (CLR) of Aleglitazar, M1, and M6 | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72, and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine | CLR was calculated as Ae0-48/AUC0-48, where Ae0-48 as amount excreted in urine from time 0 to 48 hours post-dose and AUC0-48 represents area under the concentration-time curve of the analyte in plasma over the time interval from zero to the 48 hours post-dose. |
| Apparent Non-renal Clearance (CLNR/F) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine | Plasma and urine samples were collected for this PK parameter. CLNR/F was estimated as CL/F, based on the approximated formula of CLNR/F = (CL-CLR)/F with CLR of aleglitazar being equal to zero. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. CLR was calculated as Ae0-48/AUC0-48, where Ae0-48 as amount excreted in urine from time zero to 48 hours post-dose and AUC0-48 represents area under the concentration-time curve of the analyte in plasma over the time interval from zero to the 48 hours post-dose. |
| Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | M1 and M6 are pharmacologically inactive metabolites of aleglitazar. Tmax was measured as time to reach the maximum concentration in the plasma after post-dose. |
| Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | M1 and M6 are pharmacologically inactive metabolites of aleglitazar. T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. |
| Elimination Rate Constant (Kel) of Aleglitazar | 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose | The kel is fraction of a substance that is removed per unit time measured at any particular instant. It was calculated using at least 3 concentration-time points and ideally covered more than 2 half-lives. |
| Apparent Volume of Distribution (Vz/F) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine | Vz/F is the apparent volume of distribution during terminal phase after non-intravenous administration. It was calculated as CL/F/kel, where CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity and kel as constant elimination rate of aleglitazar. |
| Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose | The cumulative amount excreted in urine Ae0-48 over the entire collection interval of 48 hours was calculated by adding the Ae of the intervals 0-4, 4-8, 8-12, 12-24, and 24-48 hours, where Ae was calculated by multiplying the urine volume within the collection interval by the associated drug concentration. |
| Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar | 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose | fe0-48 was calculated as Ae0-48/dose. The cumulative amount excreted in urine Ae0-48 over the entire collection interval of 48 hours was calculated by adding the Ae of the intervals 0-4, 4-8, 8-12, 12-24, and 24-48 hours. Ae was calculated by multiplying the urine volume within the collection interval by the associated drug concentration. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | M1 and M6 are pharmacologically inactive metabolites of aleglitazar. AUC0-48 was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. |
| Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf) | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. It was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. It was assessed using an analysis of variance model on the log-transformed values of AUCinf of aleglitazar with hepatic impairment group as factor. |
| Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | Cmax was obtained directly from the concentration-time data. |
| Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last) | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | Plasma samples were collected for this PK parameter. AUClast represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero 0 to the last quantifiable time-point post-dose. It was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. AUClast was extrapolated to AUCinf by adding the ratio of Clast/kel to the AUClast, where Clast was the last observed concentration and kel was elimination rate constant. |
| Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48) | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | AUClast represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero to the 48 hours post-dose. It was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. |
| Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine | VzF/u is an apparent volume of Unbound distribution during terminal phase after non-intravenous administration. It was calculated as CL/F/kel, where CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity and kel as constant elimination rate of aleglitazar. |
| Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine | CL/F is an apparent total clearance of the drug from plasma after oral administration. It was calculated as dose/AUCinf. AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. |
| Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Up to 6 weeks | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. |
| Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | Screening (Days -28 to -2), baseline (Day -1), Days 1 to 5, and follow-up visit (Day 10) | The ECG evaluations were performed after participants were at rest and in supine position for at least 5 minutes before recording and remain resting and supine during the recordings. ECGs parameters included heart rate (HR), RR interval, PR interval, QRS duration, QT interval, QTcB, and QTcF intervals. The normal ranges of ECG parameter values were: HR as 40-100 beats per minute, RR as 600-1500 milliseconds (msec), PR as 120-200 msec, QRS as 80-120 msec, QT as 200-500 msec, QTcB as 350-450 msec, and QTcF as 350-450 msec. Data was reported as the number of participants who had low level values (values less than the normal range) and high level values (values more than the normal range). |
| Number of Participants With Low and High Vital Signs Values | Days -28 to -2, Day -1, Days 1 to 5, and Day 10 for blood pressure and pulse rate; and Days -28 to -2, Day -1, and Day 10 for oral body temperature | Vital signs were assessed after participants had rested in a supine position for no less than 5 minutes. Vital signs included systolic blood pressure, diastolic blood pressure, pulse rate, and oral body temperature. The normal ranges of vital signs were: systolic blood pressure as 90-140 millimeter of Hg (mm Hg), diastolic blood pressure as 50-90 mm Hg, pulse rate as 45-100 beats per minute, and oral body temperature as 36.3-37.5 degree Celsius. Data was reported as the number of participants who had low level values (values less than the normal range) and high level values (values more than the normal range). |
| Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Up to 6 weeks | Laboratory parameters included hematology, coagulation, biochemistry, and urinalysis. A marked abnormality was defined as a test result which was outside of the marked abnormality range. Data was reported as the number of participants who had low level values (values less than the normal range) and high level values (values more than the normal range). |
| Mean of Fraction of Unbound Aleglitazar (fu) | 2 and 24 hours post-dose | fu was calculated using the mean of the 2-hour (reflecting Cmax) and 24-hour (reflecting Ctrough) values for each participant or, if the result of only one time-point was available, fu was the result of the available time-point. Ctrough) is a measured concentration at the end of a dosing interval at steady state. |
| AUCinf of M1 (RO4408754) and M6 (RO4583746) | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose | M1 and M6 are pharmacologically inactive metabolites of aleglitazar. AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. AUCinf was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. |
Countries
United States
Participant flow
Recruitment details
A total of 38 participants with normal hepatic function, or with mild or moderate hepatic impairment were enrolled from 30 September 2010 to 05 August 2011 at 2 study sites in the U. S.
Participants by arm
| Arm | Count |
|---|---|
| Normal Hepatic Function Participants with normal hepatic function received a single oral dose of aleglitazar 150 microgram (mcg) tablet | 18 |
| Mild Hepatic Impairment Participants with mild hepatic impairment received a single oral dose of aleglitazar 150 mcg tablet | 10 |
| Moderate Hepatic Impairment Participants with moderate hepatic impairment received a single oral dose of aleglitazar 150 mcg tablet | 10 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Total |
|---|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 5.36 | 46.7 years STANDARD_DEVIATION 8.39 | 52.8 years STANDARD_DEVIATION 6.14 | 49.3 years STANDARD_DEVIATION 6.69 |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 18 | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 18 | 0 / 10 | 1 / 10 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar
AUCinf was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The pharmacokinetics (PK) analysis population consisted of all participants who received the study drug and adhered to the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar | 98.5 hours (h)*nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 27.2 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar | 113 hours (h)*nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 41.8 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar | 151 hours (h)*nanogram (ng)/milliliter (mL) | Geometric Coefficient of Variation 29.6 |
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available.90% CI: [0.9293, 1.4182]
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available. One Participant with moderate hepatic impairment was not included in the statistical analysis of the PK parameters as there was no appropriate participant with normal hepatic function match.90% CI: [1.2468, 1.9314]
Primary
Maximum Plasma Concentration (Cmax) of Aleglitazar
Cmax was obtained directly from the concentration-time data.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The pharmacokinetics (PK) analysis population consisted of all participants who received the study drug and adhered to the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Maximum Plasma Concentration (Cmax) of Aleglitazar | 21.2 ng/mL | Geometric Coefficient of Variation 30.3 |
| Mild Hepatic Impairment | Maximum Plasma Concentration (Cmax) of Aleglitazar | 20.1 ng/mL | Geometric Coefficient of Variation 25.8 |
| Moderate Hepatic Impairment | Maximum Plasma Concentration (Cmax) of Aleglitazar | 22.1 ng/mL | Geometric Coefficient of Variation 24.4 |
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available.90% CI: [0.7908, 1.1356]
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available. One Participant with moderate hepatic impairment was not included in the statistical analysis of the PK parameters as there was no appropriate participant with normal hepatic function match.90% CI: [0.8941, 1.3002]
Secondary
Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6
The cumulative amount excreted in urine Ae0-48 over the entire collection interval of 48 hours was calculated by adding the Ae of the intervals 0-4, 4-8, 8-12, 12-24, and 24-48 hours, where Ae was calculated by multiplying the urine volume within the collection interval by the associated drug concentration.
Time frame: 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | M1 (n = 18, 10, 10) | 13.7 mcg | Geometric Coefficient of Variation 49.1 |
| Normal Hepatic Function | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 9) | NA mcg | — |
| Normal Hepatic Function | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 10) | 4.78 mcg | Geometric Coefficient of Variation 39.7 |
| Mild Hepatic Impairment | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | M1 (n = 18, 10, 10) | 21.1 mcg | Geometric Coefficient of Variation 31.8 |
| Mild Hepatic Impairment | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 9) | NA mcg | — |
| Mild Hepatic Impairment | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 10) | 6.48 mcg | Geometric Coefficient of Variation 53.2 |
| Moderate Hepatic Impairment | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 9) | NA mcg | — |
| Moderate Hepatic Impairment | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 10) | 5.81 mcg | Geometric Coefficient of Variation 37.3 |
| Moderate Hepatic Impairment | Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 | M1 (n = 18, 10, 10) | 20.5 mcg | Geometric Coefficient of Variation 47 |
Secondary
Apparent Non-renal Clearance (CLNR/F) of Aleglitazar
Plasma and urine samples were collected for this PK parameter. CLNR/F was estimated as CL/F, based on the approximated formula of CLNR/F = (CL-CLR)/F with CLR of aleglitazar being equal to zero. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. CLR was calculated as Ae0-48/AUC0-48, where Ae0-48 as amount excreted in urine from time zero to 48 hours post-dose and AUC0-48 represents area under the concentration-time curve of the analyte in plasma over the time interval from zero to the 48 hours post-dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Apparent Non-renal Clearance (CLNR/F) of Aleglitazar | 1.52 L/h | Geometric Coefficient of Variation 27.2 |
| Mild Hepatic Impairment | Apparent Non-renal Clearance (CLNR/F) of Aleglitazar | 1.33 L/h | Geometric Coefficient of Variation 41.8 |
| Moderate Hepatic Impairment | Apparent Non-renal Clearance (CLNR/F) of Aleglitazar | 0.991 L/h | Geometric Coefficient of Variation 31.5 |
Secondary
Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6
M1 and M6 are pharmacologically inactive metabolites of aleglitazar. T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 6.11 h | Geometric Coefficient of Variation 55 |
| Normal Hepatic Function | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 10) | 7.59 h | Geometric Coefficient of Variation 31.3 |
| Normal Hepatic Function | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 25.6 h | Geometric Coefficient of Variation 17.4 |
| Mild Hepatic Impairment | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 7.79 h | Geometric Coefficient of Variation 57.4 |
| Mild Hepatic Impairment | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 10) | 8.18 h | Geometric Coefficient of Variation 29.1 |
| Mild Hepatic Impairment | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 27.1 h | Geometric Coefficient of Variation 19.4 |
| Moderate Hepatic Impairment | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 10) | 8.04 h | Geometric Coefficient of Variation 19.3 |
| Moderate Hepatic Impairment | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 35.1 h | Geometric Coefficient of Variation 28.4 |
| Moderate Hepatic Impairment | Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 9.37 h | Geometric Coefficient of Variation 31.7 |
Secondary
Apparent Total Body Clearance (CL/F) of Aleglitazar
CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Apparent Total Body Clearance (CL/F) of Aleglitazar | 1.52 L/h | Geometric Coefficient of Variation 27.2 |
| Mild Hepatic Impairment | Apparent Total Body Clearance (CL/F) of Aleglitazar | 1.33 L/h | Geometric Coefficient of Variation 41.8 |
| Moderate Hepatic Impairment | Apparent Total Body Clearance (CL/F) of Aleglitazar | 0.990 L/h | Geometric Coefficient of Variation 29.6 |
Secondary
Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar
CL/F is an apparent total clearance of the drug from plasma after oral administration. It was calculated as dose/AUCinf. AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar | 1510 L/h | Geometric Coefficient of Variation 27 |
| Mild Hepatic Impairment | Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar | 1230 L/h | Geometric Coefficient of Variation 44.5 |
| Moderate Hepatic Impairment | Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar | 939 L/h | Geometric Coefficient of Variation 30 |
Secondary
Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar
VzF/u is an apparent volume of Unbound distribution during terminal phase after non-intravenous administration. It was calculated as CL/F/kel, where CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity and kel as constant elimination rate of aleglitazar.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar | 16600 L | Geometric Coefficient of Variation 29.3 |
| Mild Hepatic Impairment | Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar | 14500 L | Geometric Coefficient of Variation 19.6 |
| Moderate Hepatic Impairment | Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar | 10600 L | Geometric Coefficient of Variation 23.2 |
Secondary
Apparent Volume of Distribution (Vz/F) of Aleglitazar
Vz/F is the apparent volume of distribution during terminal phase after non-intravenous administration. It was calculated as CL/F/kel, where CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity and kel as constant elimination rate of aleglitazar.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Apparent Volume of Distribution (Vz/F) of Aleglitazar | 16.7 L | Geometric Coefficient of Variation 30.7 |
| Mild Hepatic Impairment | Apparent Volume of Distribution (Vz/F) of Aleglitazar | 15.7 L | Geometric Coefficient of Variation 22.5 |
| Moderate Hepatic Impairment | Apparent Volume of Distribution (Vz/F) of Aleglitazar | 11.5 L | Geometric Coefficient of Variation 17 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6
AUClast was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | M1 (n= 18, 10, 10) | 12.5 h*ng/mL | Geometric Coefficient of Variation 32.4 |
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | Aleglitazar (n= 18, 10, 10) | 97.5 h*ng/mL | Geometric Coefficient of Variation 27.6 |
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | M6 (n= 18, 10, 10) | 137 h*ng/mL | Geometric Coefficient of Variation 27.2 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | M1 (n= 18, 10, 10) | 15.2 h*ng/mL | Geometric Coefficient of Variation 29.6 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | Aleglitazar (n= 18, 10, 10) | 112 h*ng/mL | Geometric Coefficient of Variation 41.6 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | M6 (n= 18, 10, 10) | 151 h*ng/mL | Geometric Coefficient of Variation 52 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | Aleglitazar (n= 18, 10, 10) | 150 h*ng/mL | Geometric Coefficient of Variation 29.6 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | M6 (n= 18, 10, 10) | 186 h*ng/mL | Geometric Coefficient of Variation 35.6 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 | M1 (n= 18, 10, 10) | 22.3 h*ng/mL | Geometric Coefficient of Variation 23.6 |
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6
M1 and M6 are pharmacologically inactive metabolites of aleglitazar. AUC0-48 was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 13.8 h*ng/mL | Geometric Coefficient of Variation 31.6 |
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 10) | 97.3 h*ng/mL | Geometric Coefficient of Variation 27 |
| Normal Hepatic Function | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 112 h*ng/mL | Geometric Coefficient of Variation 25.4 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 16.4 h*ng/mL | Geometric Coefficient of Variation 29.5 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 10) | 111 h*ng/mL | Geometric Coefficient of Variation 39.6 |
| Mild Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 115 h*ng/mL | Geometric Coefficient of Variation 52.7 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 10) | 149 h*ng/mL | Geometric Coefficient of Variation 28.6 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 137 h*ng/mL | Geometric Coefficient of Variation 17.4 |
| Moderate Hepatic Impairment | Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 24.0 h*ng/mL | Geometric Coefficient of Variation 20.9 |
Secondary
Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last)
Plasma samples were collected for this PK parameter. AUClast represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero 0 to the last quantifiable time-point post-dose. It was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. AUClast was extrapolated to AUCinf by adding the ratio of Clast/kel to the AUClast, where Clast was the last observed concentration and kel was elimination rate constant.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last) | 0.0981 h*ng/mL | Geometric Coefficient of Variation 27.3 |
| Mild Hepatic Impairment | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last) | 0.121 h*ng/mL | Geometric Coefficient of Variation 44.4 |
| Moderate Hepatic Impairment | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last) | 0.158 h*ng/mL | Geometric Coefficient of Variation 29.6 |
Secondary
Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48)
AUClast represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero to the 48 hours post-dose. It was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48) | 0.0980 h*ng/mL | Geometric Coefficient of Variation 26.7 |
| Mild Hepatic Impairment | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48) | 0.120 h*ng/mL | Geometric Coefficient of Variation 40.9 |
| Moderate Hepatic Impairment | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48) | 0.158 h*ng/mL | Geometric Coefficient of Variation 29.2 |
Secondary
Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf)
AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. It was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values. It was assessed using an analysis of variance model on the log-transformed values of AUCinf of aleglitazar with hepatic impairment group as factor.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf) | 0.0992 h*ng/mL | Geometric Coefficient of Variation 27 |
| Mild Hepatic Impairment | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf) | 0.122 h*ng/mL | Geometric Coefficient of Variation 44.5 |
| Moderate Hepatic Impairment | Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf) | 0.160 h*ng/mL | Geometric Coefficient of Variation 30 |
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available.90% CI: [0.9618, 1.5789]
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available. One participant with moderate hepatic impairment was not included in the statistical analysis of the PK parameters as there was no appropriate participant with normal hepatic function match.90% CI: [1.2165, 1.9971]
Secondary
AUCinf of M1 (RO4408754) and M6 (RO4583746)
M1 and M6 are pharmacologically inactive metabolites of aleglitazar. AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity. AUCinf was calculated by non-compartmental analysis using the linear trapezoidal rule, using relative actual time values.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | AUCinf of M1 (RO4408754) and M6 (RO4583746) | M1 (n = 18, 9, 9) | 14.0 h*ng/mL | Geometric Coefficient of Variation 32.9 |
| Normal Hepatic Function | AUCinf of M1 (RO4408754) and M6 (RO4583746) | M6 (n = 18, 10, 9) | 148 h*ng/mL | Geometric Coefficient of Variation 27.8 |
| Mild Hepatic Impairment | AUCinf of M1 (RO4408754) and M6 (RO4583746) | M1 (n = 18, 9, 9) | 17.1 h*ng/mL | Geometric Coefficient of Variation 29.5 |
| Mild Hepatic Impairment | AUCinf of M1 (RO4408754) and M6 (RO4583746) | M6 (n = 18, 10, 9) | 169 h*ng/mL | Geometric Coefficient of Variation 54.3 |
| Moderate Hepatic Impairment | AUCinf of M1 (RO4408754) and M6 (RO4583746) | M1 (n = 18, 9, 9) | 24.9 h*ng/mL | Geometric Coefficient of Variation 22.4 |
| Moderate Hepatic Impairment | AUCinf of M1 (RO4408754) and M6 (RO4583746) | M6 (n = 18, 10, 9) | 247 h*ng/mL | Geometric Coefficient of Variation 35.2 |
Secondary
Cmax of M1 and M6
M1 and M6 are pharmacologically inactive metabolites of aleglitazar. Cmax was obtained directly from the concentration-time data.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | Cmax of M1 and M6 | M1 (n=18, 9, 9) | 2.00 ng/mL | Geometric Coefficient of Variation 25.7 |
| Normal Hepatic Function | Cmax of M1 and M6 | M6 (n= 18, 10, 9) | 4.59 ng/mL | Geometric Coefficient of Variation 24.5 |
| Mild Hepatic Impairment | Cmax of M1 and M6 | M1 (n=18, 9, 9) | 2.01 ng/mL | Geometric Coefficient of Variation 40.8 |
| Mild Hepatic Impairment | Cmax of M1 and M6 | M6 (n= 18, 10, 9) | 4.05 ng/mL | Geometric Coefficient of Variation 54.4 |
| Moderate Hepatic Impairment | Cmax of M1 and M6 | M1 (n=18, 9, 9) | 2.38 ng/mL | Geometric Coefficient of Variation 27.1 |
| Moderate Hepatic Impairment | Cmax of M1 and M6 | M6 (n= 18, 10, 9) | 4.05 ng/mL | Geometric Coefficient of Variation 19.7 |
Secondary
Elimination Rate Constant (Kel) of Aleglitazar
The kel is fraction of a substance that is removed per unit time measured at any particular instant. It was calculated using at least 3 concentration-time points and ideally covered more than 2 half-lives.
Time frame: 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Elimination Rate Constant (Kel) of Aleglitazar | 0.0914 1/h | Geometric Coefficient of Variation 31.3 |
| Mild Hepatic Impairment | Elimination Rate Constant (Kel) of Aleglitazar | 0.0847 1/h | Geometric Coefficient of Variation 29.1 |
| Moderate Hepatic Impairment | Elimination Rate Constant (Kel) of Aleglitazar | 0.0862 1/h | Geometric Coefficient of Variation 19.3 |
Secondary
Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar
fe0-48 was calculated as Ae0-48/dose. The cumulative amount excreted in urine Ae0-48 over the entire collection interval of 48 hours was calculated by adding the Ae of the intervals 0-4, 4-8, 8-12, 12-24, and 24-48 hours. Ae was calculated by multiplying the urine volume within the collection interval by the associated drug concentration.
Time frame: 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Normal Hepatic Function | Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar | NA mcg |
| Mild Hepatic Impairment | Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar | NA mcg |
| Moderate Hepatic Impairment | Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar | NA mcg |
Secondary
Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar
Cmax was obtained directly from the concentration-time data.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar | 0.0213 ng/mL | Geometric Coefficient of Variation 30.4 |
| Mild Hepatic Impairment | Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar | 0.0214 ng/mL | Geometric Coefficient of Variation 27.4 |
| Moderate Hepatic Impairment | Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar | 0.0257 ng/mL | Geometric Coefficient of Variation 17.2 |
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available.90% CI: [0.8049, 1.2492]
Comparison: This statistical analysis consisted of all evaluable hepatic impaired participants for whom at least one evaluable matching healthy participant was available. One participant with moderate hepatic impairment was not included in the statistical analysis of the PK parameters as there was no appropriate participant with normal hepatic function match.90% CI: [0.9836, 1.5266]
Secondary
Mean of Fraction of Unbound Aleglitazar (fu)
fu was calculated using the mean of the 2-hour (reflecting Cmax) and 24-hour (reflecting Ctrough) values for each participant or, if the result of only one time-point was available, fu was the result of the available time-point. Ctrough) is a measured concentration at the end of a dosing interval at steady state.
Time frame: 2 and 24 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed. Only participants with data available for specific study drug/metabolite were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function | Mean of Fraction of Unbound Aleglitazar (fu) | 0.101 Percentage | Geometric Coefficient of Variation 10.2 |
| Mild Hepatic Impairment | Mean of Fraction of Unbound Aleglitazar (fu) | 0.111 Percentage | Geometric Coefficient of Variation 7.4 |
| Moderate Hepatic Impairment | Mean of Fraction of Unbound Aleglitazar (fu) | 0.114 Percentage | Geometric Coefficient of Variation 15.3 |
Secondary
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Time frame: Up to 6 weeks
Population: The safety analysis consisted of all participants who had received the single dose of the study drug (aleglitazar), whether prematurely withdrawn from the study or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Any AEs | 3 participants |
| Normal Hepatic Function | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Any SAEs | 0 participants |
| Normal Hepatic Function | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Death | 0 participants |
| Normal Hepatic Function | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Study discontinuation | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Study discontinuation | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Any AEs | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Death | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Any SAEs | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Study discontinuation | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Any SAEs | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Death | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation | Any AEs | 2 participants |
Secondary
Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values
The ECG evaluations were performed after participants were at rest and in supine position for at least 5 minutes before recording and remain resting and supine during the recordings. ECGs parameters included heart rate (HR), RR interval, PR interval, QRS duration, QT interval, QTcB, and QTcF intervals. The normal ranges of ECG parameter values were: HR as 40-100 beats per minute, RR as 600-1500 milliseconds (msec), PR as 120-200 msec, QRS as 80-120 msec, QT as 200-500 msec, QTcB as 350-450 msec, and QTcF as 350-450 msec. Data was reported as the number of participants who had low level values (values less than the normal range) and high level values (values more than the normal range).
Time frame: Screening (Days -28 to -2), baseline (Day -1), Days 1 to 5, and follow-up visit (Day 10)
Population: The safety analysis consisted of all participants who had received the single dose of the study drug (aleglitazar), whether prematurely withdrawn from the study or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcB - high | 2 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | PR - low | 2 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | RR - high | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QT - low | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QRS - high | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | HR - low | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QT - high | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QRS - low | 6 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcB - low | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | RR - low | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcF - low | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | HR - high | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | PR - high | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcF - high | 2 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcB - high | 3 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | HR - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | HR - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | RR - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | RR - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | PR - high | 1 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | PR - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QRS - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QRS - low | 1 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QT - high | 1 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QT - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcB - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcF - high | 2 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcF - low | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcF - high | 3 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QT - low | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | PR - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | RR - low | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcB - high | 4 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | RR - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | HR - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcB - low | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | HR - low | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QRS - low | 6 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QRS - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QTcF - low | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | QT - high | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values | PR - low | 3 participants |
Secondary
Number of Participants With Low and High Vital Signs Values
Vital signs were assessed after participants had rested in a supine position for no less than 5 minutes. Vital signs included systolic blood pressure, diastolic blood pressure, pulse rate, and oral body temperature. The normal ranges of vital signs were: systolic blood pressure as 90-140 millimeter of Hg (mm Hg), diastolic blood pressure as 50-90 mm Hg, pulse rate as 45-100 beats per minute, and oral body temperature as 36.3-37.5 degree Celsius. Data was reported as the number of participants who had low level values (values less than the normal range) and high level values (values more than the normal range).
Time frame: Days -28 to -2, Day -1, Days 1 to 5, and Day 10 for blood pressure and pulse rate; and Days -28 to -2, Day -1, and Day 10 for oral body temperature
Population: The safety analysis consisted of all participants who had received the single dose of the study drug (aleglitazar), whether prematurely withdrawn from the study or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Systolic blood pressure - high | 4 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Systolic blood pressure - low | 2 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Diastolic blood pressure - high | 2 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Diastolic blood pressure - low | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Pulse rate - high | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Pulse rate - low | 1 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Oral body temperature - high | 0 participants |
| Normal Hepatic Function | Number of Participants With Low and High Vital Signs Values | Oral body temperature - low | 11 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Diastolic blood pressure - high | 3 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Oral body temperature - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Diastolic blood pressure - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Pulse rate - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Pulse rate - low | 2 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Systolic blood pressure - high | 4 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Systolic blood pressure - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Oral body temperature - low | 4 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Diastolic blood pressure - high | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Systolic blood pressure - low | 2 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Systolic blood pressure - high | 3 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Diastolic blood pressure - low | 2 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Oral body temperature - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Pulse rate - low | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Pulse rate - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Low and High Vital Signs Values | Oral body temperature - low | 7 participants |
Secondary
Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters
Laboratory parameters included hematology, coagulation, biochemistry, and urinalysis. A marked abnormality was defined as a test result which was outside of the marked abnormality range. Data was reported as the number of participants who had low level values (values less than the normal range) and high level values (values more than the normal range).
Time frame: Up to 6 weeks
Population: The safety analysis consisted of all participants who had received the single dose of the study drug (aleglitazar), whether prematurely withdrawn from the study or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Lymphocytes - low | 0 participants |
| Normal Hepatic Function | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Bicarbonate - high | 0 participants |
| Normal Hepatic Function | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Phosphate - high | 0 participants |
| Normal Hepatic Function | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Blood - high | 2 participants |
| Normal Hepatic Function | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Glucose - high | 0 participants |
| Normal Hepatic Function | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Protein - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Protein - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Lymphocytes - low | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Blood - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Glucose - high | 0 participants |
| Mild Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Bicarbonate - high | 1 participants |
| Mild Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Phosphate - high | 0 participants |
| Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Bicarbonate - high | 2 participants |
| Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Phosphate - high | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Protein - high | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Blood - high | 3 participants |
| Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Lymphocytes - low | 1 participants |
| Moderate Hepatic Impairment | Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters | Glucose - high | 3 participants |
Secondary
Renal Clearance (CLR) of Aleglitazar, M1, and M6
CLR was calculated as Ae0-48/AUC0-48, where Ae0-48 as amount excreted in urine from time 0 to 48 hours post-dose and AUC0-48 represents area under the concentration-time curve of the analyte in plasma over the time interval from zero to the 48 hours post-dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72, and 96 hours post-dose for plasma; 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose for urine
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol. Only participants with data available for specific metabolite were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Hepatic Function | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 0.994 L/h | Geometric Coefficient of Variation 68.5 |
| Normal Hepatic Function | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 9) | NA L/h | — |
| Normal Hepatic Function | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 0.0427 L/h | Geometric Coefficient of Variation 31.4 |
| Mild Hepatic Impairment | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 1.26 L/h | Geometric Coefficient of Variation 48.5 |
| Mild Hepatic Impairment | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 9) | NA L/h | — |
| Mild Hepatic Impairment | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 0.0565 L/h | Geometric Coefficient of Variation 28.4 |
| Moderate Hepatic Impairment | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | Aleglitazar (n = 18, 10, 9) | NA L/h | — |
| Moderate Hepatic Impairment | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | M6 (n = 18, 10, 9) | 0.0454 L/h | Geometric Coefficient of Variation 19.9 |
| Moderate Hepatic Impairment | Renal Clearance (CLR) of Aleglitazar, M1, and M6 | M1 (n = 18, 9, 9) | 0.857 L/h | Geometric Coefficient of Variation 46.6 |
Secondary
Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6
M1 and M6 are pharmacologically inactive metabolites of aleglitazar. Tmax was measured as time to reach the maximum concentration in the plasma after post-dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Population: The PK analysis population consisted of all participants who received the study drug and adhered to the protocol.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Normal Hepatic Function | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | Aleglitazar | 1.00 h |
| Normal Hepatic Function | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | M6 | 9.00 h |
| Normal Hepatic Function | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | M1 | 2.01 h |
| Mild Hepatic Impairment | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | Aleglitazar | 1.00 h |
| Mild Hepatic Impairment | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | M1 | 3.50 h |
| Mild Hepatic Impairment | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | M6 | 9.00 h |
| Moderate Hepatic Impairment | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | Aleglitazar | 1.00 h |
| Moderate Hepatic Impairment | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | M6 | 24.0 h |
| Moderate Hepatic Impairment | Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 | M1 | 4.00 h |