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Phase 1 N=28 Treatment

Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

Hepatic Impairment

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

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Alectinib (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Dec 2016

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

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.

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.

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