Phase 1
N=28
Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib
Hepatic Impairment
Bottom Line
View on ClinicalTrials.gov: NCT02621047 ↗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
| Outcome | Result | p-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
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.