Mode
Text Size
Log in / Sign up
Phase 1 Completed N=28 Treatment

Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

Source: ClinicalTrials.gov NCT02621047 ↗
Enrolled (actual)
28
Serious AEs
3.6%
Results posted
Aug 2018
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of Total Alectinib — 107; 83.6; 85.5; 85.1 nanograms per milliliter (ng/mL)

Summary

This is a multicenter, non-randomized, single-dose, open-label study conducted in male and surgically sterile or post-menopausal female participants with stable chronic hepatic impairment and in healthy participants matched by age, gender, and body weight to assess the effect of hepatic impairment on the pharmacokinetics of alectinib.

Outcome Measures

OutcomeResultp-value
PRIMARY
Maximum Observed Plasma Concentration (Cmax) of Total Alectinib
107; 83.6; 85.5; 85.1 —
PRIMARY
Cmax of Unbound Alectinib
24.0; 16.2; 16.1; 12.3 —
PRIMARY
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib
2920; 1830; 3850; 1750 —
PRIMARY
AUC 0-inf for Unbound Alectinib
659; 355; 725; 254 —
PRIMARY
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib
2820; 1740; 3710; 1630 —
PRIMARY
AUC 0-last for Unbound Alectinib
636; 337; 699; 236 —
SECONDARY
Cmax of Total Metabolite of Alectinib (M4)
19.3; 29.8; 17.5; 28.7 —
SECONDARY
Cmax of Unbound M4
17.6; 20.6; 8.26; 14.0 —
SECONDARY
Cmax of Total Combined Alectinib and M4 (Alectinib + M4)
266; 229; 214; 218 —
SECONDARY
Cmax of Unbound Alectinib + M4
87.0; 75.9; 48.9; 50.6 —
SECONDARY
AUC 0-inf of Total M4
583; 718; 465; 709 —
SECONDARY
AUC 0-inf of Unbound M4
516; 497; 220; 345 —
SECONDARY
AUC 0-inf of Total Alectinib + M4
7340; 5380; 9020; 5120 —
SECONDARY
AUC 0-inf of Unbound Alectinib + M4
2420; 1800; 1960; 1250 —
SECONDARY
AUC 0-last of Total M4
475; 648; 363; 631 —
SECONDARY
AUC 0-last of Unbound M4
433; 448; 172; 308 —
SECONDARY
AUC 0-last of Total Alectinib + M4
7160; 5170; 8700; 4830 —
SECONDARY
AUC 0-last of Unbound Alectinib + M4
2390; 1750; 1890; 1200 —
SECONDARY
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib
6.04; 5.97; 7.02; 4.97 —
SECONDARY
Tmax for Total M4
8.10; 7.88; 8.00; 8.05 —
SECONDARY
Apparent Terminal Half-life (t1/2) of Total Alectinib
26.1; 20.1; 39.3; 22.2 —
SECONDARY
t1/2 of Total M4
24.5; 19.3; 30.5; 20.1 —
SECONDARY
Apparent Oral Clearance (CL/F) of Total Alectinib
103; 164; 77.9; 171 —
SECONDARY
CL/F of Unbound Alectinib
455; 845; 414; 1180 —
SECONDARY
Apparent Volume of Distribution (Vz/F) for Total Alectinib
3870; 4760; 4410; 5490 —
SECONDARY
Vz/F for Unbound Alectinib
17200; 24500; 23400; 37800 —
SECONDARY
Fraction of Drug Unbound (fu) of Total Alectinib
0.225; 0.194; 0.188; 0.145 —

Eligibility Criteria

Inclusion Criteria

All Participants

  • Body mass index between 18 to 35 kilograms per square meter (kg/m^2) inclusive and weight greater than (>) 50 kilograms (kg)
  • Female participants must be surgically sterile or post-menopausal
  • Male participants and their partners of child-bearing potential must be willing to use 2 effective methods of contraception, one of which must be a barrier method

Participants with Hepatic Impairment

  • Documented chronic stable liver disease (Child-Pugh Class A, B or C)

Exclusion Criteria

All Participants

  • Pregnant or lactating women, males with female partners who are pregnant or lactating, or women of child bearing potential
  • Positive test for drugs of abuse or alcohol
  • Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever time period is longer) or 6 months for biologic therapies prior to study drug administration
  • History of hypersensitivity to any of the additives in the alectinib formulation
  • Participants under judicial supervision, guardianship, or curatorship
  • History of severe drug-related allergic reactions or drug-induced hepatotoxicity

Healthy Participants

  • Use of any medications (prescription or over-the-counter), within 2 weeks or 5 half-lives (whichever longer) prior to study drug administration
  • Use of any herbal supplements or any metabolic inducers within 4 weeks, or 5 half-lives (whichever is longer) prior to study drug administration

Participants with Hepatic Impairment

  • Positive screening test for human immunodeficiency virus (HIV)
  • History of liver transplantation
  • Hepatocellular carcinoma or acute liver disease
  • Severe ascites at screening or admission to the clinic
  • Recent history (past 2 years) or current severe hepatic encephalopathy (Grade 3 or higher)
  • Any evidence of progressive liver disease within the last 4 weeks
  • Presence of surgically created or transjugular intrahepatic portal systemic shunts
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02621047). 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. Informational only — not medical advice.

Back to search