Phase 1
N=38
A Study of The Effect of Hepatic Impairment on The Pharmacokinetics of Aleglitazar
Healthy Volunteer
Bottom Line
View on ClinicalTrials.gov: NCT01197911 ↗Enrolled (actual)
38
Serious AEs
2.6%
Results posted
Dec 2015
Primary outcome: Primary: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar — 98.5; 113; 151 hours (h)*nanogram (ng)/milliliter (mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- aleglitazar (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Aug 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar |
98.5; 113; 151 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Aleglitazar |
21.2; 20.1; 22.1 | — |
| SECONDARY AUCinf of M1 (RO4408754) and M6 (RO4583746) |
14.0; 17.1; 24.9; 148; 169; 247 | — |
| SECONDARY Cmax of M1 and M6 |
2.00; 2.01; 2.38; 4.59; 4.05; 4.05 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6 |
97.3; 111; 149; 13.8; 16.4; 24.0 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6 |
97.5; 112; 150; 12.5; 15.2; 22.3 | — |
| SECONDARY Apparent Total Body Clearance (CL/F) of Aleglitazar |
1.52; 1.33; 0.990 | — |
| SECONDARY Renal Clearance (CLR) of Aleglitazar, M1, and M6 |
NA; NA; NA; 0.994; 1.26; 0.857 | — |
| SECONDARY Apparent Non-renal Clearance (CLNR/F) of Aleglitazar |
1.52; 1.33; 0.991 | — |
| SECONDARY Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6 |
1.00; 1.00; 1.00; 2.01; 3.50; 4.00 | — |
| SECONDARY Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6 |
7.59; 8.18; 8.04; 6.11; 7.79; 9.37 | — |
| SECONDARY Elimination Rate Constant (Kel) of Aleglitazar |
0.0914; 0.0847; 0.0862 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of Aleglitazar |
16.7; 15.7; 11.5 | — |
| SECONDARY Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6 |
NA; NA; NA; 13.7; 21.1; 20.5 | — |
| SECONDARY Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar |
NA; NA; NA | — |
| SECONDARY Mean of Fraction of Unbound Aleglitazar (fu) |
0.101; 0.111; 0.114 | — |
| SECONDARY Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf) |
0.0992; 0.122; 0.160 | — |
| SECONDARY Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar |
0.0213; 0.0214; 0.0257 | — |
| SECONDARY Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last) |
0.0981; 0.121; 0.158 | — |
| SECONDARY Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48) |
0.0980; 0.120; 0.158 | — |
| SECONDARY Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar |
16600; 14500; 10600 | — |
| SECONDARY Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar |
1510; 1230; 939 | — |
| SECONDARY Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation |
3; 0; 2; 0; 0; 1 | — |
| SECONDARY Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Low and High Vital Signs Values |
4; 4; 3; 2; 0; 2 | — |
| SECONDARY Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters |
0; 0; 1; 0; 1; 2 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01197911). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.