Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

NCT02621047 | Completed Phase 1 Results

• 2 other identifiers: NP297832015-002976-25
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Hepatic Impairment

Keywords

Healthy volunteer; Alectinib; Hepatic impairment

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) of Total Alectinib

  Total alectinib = unbound alectinib plus alectinib bound to plasma proteins

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• Cmax of Unbound Alectinib

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib

  Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. AUC 0-inf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• AUC 0-inf for Unbound Alectinib

  AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib

  Total alectinib = unbound alectinib plus alectinib bound to plasma proteins

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• AUC 0-last for Unbound Alectinib

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

Secondary Outcomes (21)

• Cmax of Total Metabolite of Alectinib (M4)

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• Cmax of Unbound M4

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• Cmax of Total Combined Alectinib and M4 (Alectinib + M4)

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• Cmax of Unbound Alectinib + M4

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

• AUC 0-inf of Total M4

  Predose (0 hour), and at 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours postdose (Dosing day = Day 1)

Study Arms (3)

Alectinib: Moderate Hepatic Impairment

EXPERIMENTAL

Participants with moderate hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 milligrams (mg) on Day 1.

Drug: Alectinib

Alectinib: Severe Hepatic Impairment

EXPERIMENTAL

Participants with severe hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 mg on Day 1.

Drug: Alectinib

Alectinib: Normal Hepatic Function

EXPERIMENTAL

Participants with normal hepatic function will receive alectinib at a single oral dose of 300 mg on Day 1.

Drug: Alectinib

Interventions

Alectinib DRUG

Participants will receive alectinib as per the dosage schedule mentioned in arm description.

Alectinib: Moderate Hepatic Impairment; Alectinib: Normal Hepatic Function; Alectinib: Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Pharmaceutical Research Associates CZ, s.r.o.

Prague, 170 00, Czechia

Location

Summit Clinical Research s.r.o.; Oddelenie internej mediciny a klinickej farmakologie

Bratislava, 831 01, Slovakia

Location

Related Publications (1)

• Morcos PN, Cleary Y, Sturm-Pellanda C, Guerini E, Abt M, Donzelli M, Vazvaei F, Balas B, Parrott N, Yu L. Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib. J Clin Pharmacol. 2018 Dec;58(12):1618-1628. doi: 10.1002/jcph.1286. Epub 2018 Jul 27.

  PMID: 30052269 DERIVED

MeSH Terms

Interventions

alectinib

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: December 4, 2015
• Primary Completion: December 8, 2016
• Study Completion: December 8, 2016
• Last Updated: August 24, 2018
• Results First Posted: August 24, 2018

Record last verified: 2017-11

Locations

CZ (1); SL (1)