Clinical trial NCT01197911: A Study of The Effect of Hepatic Impairment on The Pharmacokinetics of Aleglitazar
Official title: The Effect of Hepatic Impairment on the Pharmacokinetics of Aleglitazar: A Multiple-centre, Open-label Study Following a Single Oral Dose of Aleglitazar to Subjects With Mild or Moderate Hepatic Impairment and Healthy Subjects With Normal Hepatic Function.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-09-09
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.


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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Aleglitazar
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Aleglitazar
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
Secondary outcomes:
measure: AUCinf of M1 (RO4408754) and M6 (RO4583746)
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Cmax of M1 and M6
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Post-dose (AUC0-48) of Aleglitazar, M1, and M6
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From 0 to the Last Quantifiable Time-point Post-dose (AUClast) of Aleglitazar, M1, and M6
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Apparent Total Body Clearance (CL/F) of Aleglitazar
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Renal Clearance (CLR) of Aleglitazar, M1, and M6
timeFrame: 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
measure: Apparent Non-renal Clearance (CLNR/F) of Aleglitazar
timeFrame: 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
measure: Time of Maximum Plasma Concentration (Tmax) of Aleglitazar, M1, and M6
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Apparent Terminal Half-life (t½) of Aleglitazar, M1, and M6
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Elimination Rate Constant (Kel) of Aleglitazar
timeFrame: 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) of Aleglitazar
timeFrame: 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
measure: Amount Excreted in Urine From Time 0 to 48 Hours Post-dose (Ae0-48) of Aleglitazar, M1, and M6
timeFrame: 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
measure: Fraction of Drug Excreted in Urine From Time 0 to 48 Hours Post-dose (fe0-48) of Aleglitazar
timeFrame: 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose
measure: Mean of Fraction of Unbound Aleglitazar (fu)
timeFrame: 2 and 24 hours post-dose
measure: Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to Infinity (AUCu,Inf)
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Maximum Unbound Plasma Concentration (Cmax,u) of Aleglitazar
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From 0 to the Last Quantifiable Time-point Post-dose (AUCu,Last)
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Area Under the Unbound Plasma Concentration-time Curve of Aleglitazar From Time 0 to 48 Hours Post-dose (AUCu,0-48)
timeFrame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, 15, 24, 36, 48, 72 and 96 hours post-dose
measure: Apparent Unbound Volume of Distribution (Vz/Fu) of Aleglitazar
timeFrame: 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
measure: Apparent Unbound Total Body Clearance (CL/Fu) of Aleglitazar
timeFrame: 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
measure: Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), Death, and Study Discontinuation
timeFrame: Up to 6 weeks
measure: Number of Participants With Low and High Electrocardiograms (ECGs) Parameter Values
timeFrame: Screening (Days -28 to -2), baseline (Day -1), Days 1 to 5, and follow-up visit (Day 10)
measure: Number of Participants With Low and High Vital Signs Values
timeFrame: 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
measure: Number of Participants With Marked Abnormalities in Clinical Laboratory Parameters
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Orlando
country: United States
state: Florida
city: Knoxville
country: United States
state: Tennessee
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: