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Trial record 66 of 1643 for:    Slovakia

Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

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ClinicalTrials.gov Identifier: NCT02621047
Recruitment Status : Completed
First Posted : December 3, 2015
Results First Posted : August 24, 2018
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Hepatic Impairment Drug: Alectinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib: A Multiple-Center, Open-Label Study Following Single Oral Dosing of Alectinib to Subjects With Hepatic Impairment and Matched Healthy Subjects With Normal Hepatic Function
Actual Study Start Date : December 4, 2015
Actual Primary Completion Date : December 8, 2016
Actual Study Completion Date : December 8, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Alectinib

Arm Intervention/treatment
Experimental: Alectinib: Moderate Hepatic Impairment
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
Participants will receive alectinib as per the dosage schedule mentioned in arm description.

Experimental: Alectinib: Severe Hepatic Impairment
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
Participants will receive alectinib as per the dosage schedule mentioned in arm description.

Experimental: Alectinib: Normal Hepatic Function
Participants with normal hepatic function will receive alectinib at a single oral dose of 300 mg on Day 1.
Drug: Alectinib
Participants will receive alectinib as per the dosage schedule mentioned in arm description.




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins

  2. Cmax of Unbound Alectinib [ Time Frame: 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) ]
  3. Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC 0-inf) for Total Alectinib [ Time Frame: 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) ]
    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.

  4. AUC 0-inf for Unbound Alectinib [ Time Frame: 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 = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.

  5. Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measureable Concentration (AUC 0-last) for Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins

  6. AUC 0-last for Unbound Alectinib [ Time Frame: 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 Outcome Measures :
  1. Cmax of Total Metabolite of Alectinib (M4) [ Time Frame: 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) ]
    Total M4 = unbound M4 plus M4 bound to plasma proteins

  2. Cmax of Unbound M4 [ Time Frame: 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) ]
  3. Cmax of Total Combined Alectinib and M4 (Alectinib + M4) [ Time Frame: 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) ]
    Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins

  4. Cmax of Unbound Alectinib + M4 [ Time Frame: 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) ]
  5. AUC 0-inf of Total M4 [ Time Frame: 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) ]
    Total M4 = unbound M4 plus M4 bound to plasma proteins. 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.

  6. AUC 0-inf of Unbound M4 [ Time Frame: 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 = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.

  7. AUC 0-inf of Total Alectinib + M4 [ Time Frame: 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) ]
    Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins. 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.

  8. AUC 0-inf of Unbound Alectinib + M4 [ Time Frame: 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 = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.

  9. AUC 0-last of Total M4 [ Time Frame: 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) ]
    Total M4 = unbound M4 plus M4 bound to plasma proteins

  10. AUC 0-last of Unbound M4 [ Time Frame: 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) ]
  11. AUC 0-last of Total Alectinib + M4 [ Time Frame: 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) ]
    Total alectinib + M4 = unbound alectinib + M4 plus alectinib + M4 bound to plasma proteins

  12. AUC 0-last of Unbound Alectinib + M4 [ Time Frame: 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) ]
  13. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins

  14. Tmax for Total M4 [ Time Frame: 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) ]
    Total M4 = unbound M4 plus M4 bound to plasma proteins

  15. Apparent Terminal Half-life (t1/2) of Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half.

  16. t1/2 of Total M4 [ Time Frame: 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) ]
    Total M4 = unbound M4 plus M4 bound to plasma proteins. t1/2 = the time measured for the plasma concentration to decrease by one half.

  17. Apparent Oral Clearance (CL/F) of Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability.

  18. CL/F of Unbound Alectinib [ Time Frame: 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) ]
    Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability.

  19. Apparent Volume of Distribution (Vz/F) for Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed.

  20. Vz/F for Unbound Alectinib [ Time Frame: 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) ]
    Volume of distribution is defined as the theoretical volume which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed.

  21. Fraction of Drug Unbound (fu) of Total Alectinib [ Time Frame: 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) ]
    Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. fu = ratio of unbound alectinib to total alectinib multiplied by 100.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02621047


Locations
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Czechia
Pharmaceutical Research Associates CZ, s.r.o.
Praha 7, Czechia, 170 00
Slovakia
Summit Clinical Research s.r.o.; Oddelenie internej mediciny a klinickej farmakologie
Bratislava, Slovakia, 831 01
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02621047     History of Changes
Other Study ID Numbers: NP29783
2015-002976-25 ( EudraCT Number )
First Posted: December 3, 2015    Key Record Dates
Results First Posted: August 24, 2018
Last Update Posted: August 24, 2018
Last Verified: November 2017
Keywords provided by Hoffmann-La Roche:
Healthy volunteer
Alectinib
Hepatic impairment
Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases