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A Study Examining the Bioequivalence of 3 Alectinib (RO5424802) Test Formulations to a Reference Formulation of in Healthy Participants

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ClinicalTrials.gov Identifier: NCT02074553
Recruitment Status : Completed
First Posted : February 28, 2014
Results First Posted : October 18, 2016
Last Update Posted : October 18, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This 2-part, single center, open-label, randomized, single-dose, 4-sequence, 4-period cross-over study will compare the bioequivalence of three test alectinib capsule formulations with the reference capsule formulation in healthy adult participants. All participants in both fasted (Part 1) and fed (Part 2) conditions of the study will receive each of 4 treatments: Treatment A (alectinib with 50 percent [%] sodium lauryl sulfate [SLS] [reference]), Treatment B (alectinib with 25% SLS [test]), Treatment C (alectinib with 12.5% SLS [test]), and Treatment D (alectinib with 3% SLS [test]) in a randomized sequence. Each treatment will be given as a single 600 milligrams (mg) oral administration in an upright position on Day 1 in a fed or fasted condition, followed by a 10-day washout period.

Condition or disease Intervention/treatment Phase
Healthy Volunteer Drug: Part 1 (Fasted): Treatment A Drug: Part 1 (Fasted): Treatment B Drug: Part 1 (Fasted): Treatment C Drug: Part 1 (Fasted): Treatment D Drug: Part 2 (Fed): Treatment A Drug: Part 2 (Fed): Treatment B Drug: Part 2 (Fed): Treatment C Drug: Part 2 (Fed): Treatment D Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Single Dose, Cross-Over Study to Investigate the Bioequivalence of Three RO5424802 Test Formulations Versus a Reference Formulation Following Oral Administration in Healthy Subjects
Study Start Date : February 2014
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Arm Intervention/treatment
Experimental: Part 1 (Fasted): Treatment A then B then C then D
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib as a capsule formulation (four 150 mg capsules) orally in Part 1 of the study according to following treatment sequences. Treatment A (Reference Treatment: formulation containing 50% SLS) on Day 1 of the first intervention period; then Treatment B (Test Treatment: formulation containing 25% SLS) on Day 1 of second intervention period (Day 11); then Treatment C (Test Treatment: formulation containing 12.5% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment D (Test Treatment: formulation containing 3% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 1 (Fasted): Treatment A
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment B
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment C
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment D
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.

Experimental: Part 1 (Fasted): Treatment B then D then A then C
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib as a capsule formulation orally in Part 1 of the study according to following treatment sequences. Treatment B (formulation containing 25% SLS) on Day 1 of the first intervention period; then Treatment D (formulation containing 3% SLS) on Day 1 of second intervention period (Day 11); then Treatment A (formulation containing 50% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment C (formulation containing 12.5% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 1 (Fasted): Treatment A
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment B
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment C
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment D
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.

Experimental: Part 1 (Fasted): Treatment C then A then D then B
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib as a capsule formulation orally in Part 1 of the study according to following treatment sequences. Treatment C (formulation containing 12.5% SLS) on Day 1 of the first intervention period; then Treatment A (formulation containing 50% SLS) on Day 1 of second intervention period (Day 11); then Treatment D (formulation containing 3% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment B (formulation containing 25% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 1 (Fasted): Treatment A
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment B
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment C
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment D
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.

Experimental: Part 1 (Fasted): Treatment D then C then B then A
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib as a capsule formulation orally in Part 1 of the study according to following treatment sequences. Treatment D (formulation containing 3% SLS) on Day 1 of the first intervention period; then Treatment C (formulation containing 12.5% SLS) on Day 1 of second intervention period (Day 11); then Treatment B (formulation containing 25% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment A (formulation containing 50% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 1 (Fasted): Treatment A
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment B
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment C
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 1.

Drug: Part 1 (Fasted): Treatment D
Participants following an overnight fast of at least 10 hours will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 1.

Experimental: Part 2 (Fed): Treatment A then B then C then D
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal will receive 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment A (formulation containing 50% SLS) on Day 1 of the first intervention period; then Treatment B (formulation containing 25% SLS) on Day 1 of second intervention period (Day 11); then Treatment C (formulation containing 12.5% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment D (formulation containing 3% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 2 (Fed): Treatment A
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment B
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment C
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment D
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.

Experimental: Part 2 (Fed): Treatment B then D then A then C
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal will receive 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment B (formulation containing 25% SLS) on Day 1 of the first intervention period; then Treatment D (formulation containing 3% SLS) on Day 1 of second intervention period (Day 11); then Treatment A (formulation containing 50% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment C (formulation containing 12.5% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 2 (Fed): Treatment A
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment B
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment C
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment D
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.

Experimental: Part 2 (Fed): Treatment C then A then D then B
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal will receive 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment C (formulation containing 12.5% SLS) on Day 1 of the first intervention period; then Treatment A (formulation containing 50% SLS) on Day 1 of second intervention period (Day 11); then Treatment D (formulation containing 3% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment B (formulation containing 25% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 2 (Fed): Treatment A
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment B
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment C
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment D
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.

Experimental: Part 2 (Fed): Treatment D then C then B then A
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after start of the meal will receive 600 mg of alectinib as a capsule formulation orally in Part 2 of the study according to following treatment sequences. Treatment D (formulation containing 3% SLS) on Day 1 of the first intervention period; then Treatment C (formulation containing 12.5% SLS) on Day 1 of second intervention period (Day 11); then Treatment B (formulation containing 25% SLS) on Day 1 of third intervention period (Day 21); followed by Treatment A (formulation containing 50% SLS) on Day 1 of fourth intervention period (Day 31). A washout period of at least 10 days will be maintained between each intervention period.
Drug: Part 2 (Fed): Treatment A
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment A (capsule formulation containing 50% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment B
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment B (capsule formulation containing 25% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment C
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment C (capsule formulation containing 12.5% SLS) on Day 1 of any of the four intervention periods in Part 2.

Drug: Part 2 (Fed): Treatment D
Participants following an overnight fast of at least 10 hours will eat a high-fat, high-calorie meal in 30 minutes or less and 30 minutes after the start of the meal will receive 600 mg of alectinib orally as Treatment D (capsule formulation containing 3% SLS) on Day 1 of any of the four intervention periods in Part 2.




Primary Outcome Measures :
  1. Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-inf) is the area under the alectinib plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in nanogram times (*) hour per milliliter (ng*hour/mL).

  2. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-last) is the area under the alectinib plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.

  3. Maximum Observed Plasma Concentration (Cmax) of Alectinib [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Cmax is the maximum observed plasma alectinib concentration, presented in nanogram per milliliter (ng/mL).


Secondary Outcome Measures :
  1. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Tmax is the time from alectinib administration to reach Cmax for alectinib.

  2. Cmax of RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Cmax is the maximum observed plasma RO5468924 concentration, presented in ng/mL. RO5468924 is the major pharmacologically active metabolite of alectinib.

  3. Tmax of RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Tmax is the time from alectinib administration to reach Cmax for RO5468924 (the major pharmacologically active metabolite of alectinib).

  4. AUC(0-inf) of RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-inf) is the area under the RO5468924 plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). RO5468924 is the major pharmacologically active metabolite of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in ng*hour/mL.

  5. AUC(0-last) of RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-last) is the area under the RO5468924 plasma concentration versus time curve from time zero to the time of last measured concentration of RO5468924. RO5468924 is the major pharmacologically active metabolite of alectinib. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.

  6. Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Plasma terminal half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half. RO5468924 is the major pharmacologically active metabolite of alectinib.

  7. Elimination Rate Constant (Kel) of Alectinib and RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    First-order terminal elimination rate constant (Kel) was calculated as the negative slope of the linear regression of the terminal phase in plasma alectinib and RO5468924 concentration versus time profile using appropriate time points. RO5468924 is the major pharmacologically active metabolite of alectinib.

  8. Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf) [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-inf) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib + RO5468924 over time. AUC(0-inf) is presented in nanomoles times (*) hour per liter (nmol*hour/L).

  9. Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Cmax is the maximum observed molar plasma concentration for alectinib + RO5468924 (major pharmacologically active metabolite of alectinib). Cmax is presented in nanomoles per liter (nmol/L).

  10. Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-last) [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-last) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero to the time of last measured concentration of alectinib + RO5468924. AUC(0-last) is presented in nmol*hour/L.

  11. Apparent Oral Clearance (CL/F) of Alectinib [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Clearance of a drug 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 fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  12. Apparent Volume of Distribution (Vz/F) of Alectinib [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Volume of distribution is defined as the theoretical volume in 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 (Vz/F) is influenced by the fraction of drug absorbed.

  13. Percent Extrapolated AUC(0-inf) (AUC%Extrap[0-inf]) for Alectinib and RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    The AUC%extrap(0-inf), that is, area obtained after extrapolation from Tlast to infinity is calculated by using the formula AUC%extrap(0-inf) = 100*(AUC[0-inf] minus AUC[0-last])/AUC(0-inf); where AUC(0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time and AUC(0-last) is area under the plasma concentration time-curve from zero (pre-dose) to the time of last measured concentration. The function of this parameter is to provide information about what percentage of the theoretical curve AUC(0-inf) was possible to determine experimentally (AUC0-last).

  14. Adjusted r^2 Value (Rsq) for Regression Estimation of Kel for Alectinib and RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
  15. Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf) [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-inf) is presented.

  16. Molecular Weight Adjusted M/P Ratio for AUC(0-last) [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    AUC(0-last) is the area under the plasma concentration versus time curve from time zero to the time of last measured concentration. AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-last) is presented.

  17. Molecular Weight Adjusted M/P Ratio for Cmax [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Cmax is the maximum observed plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib). The molecular weight adjusted M/P ratio (RO5468924/alectinib) for Cmax is presented.

  18. Time to Reach Last Quantifiable Plasma Concentration (Tlast) of Alectinib and RO5468924 [ Time Frame: Predose (0 hour), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, and 96 hours postdose ]
    Tlast is the time from alectinib administration to reach last quantifiable concentration of alectinib and its major pharmacologically active metabolite RO5468924.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and female participants. Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, and a complete physical examination
  • Body mass index between 18 to 32 kilograms per meter-squared (kg/m^2) inclusive
  • Non-smoking participants and former smoking participants who have not smoked for the past 6 months before first study drug dosing
  • Female participants must be surgically sterile or postmenopausal for the past year
  • Male participants and their partners of childbearing potential must be willing to use two effective methods of contraception, one of which must be a barrier method (for example, condom) during the study and for 90 days after the last drug administration
  • Willing to abstain from xanthine-containing beverages and food (coffee, tea, cola, chocolate, and "energy drinks") from 72 hours prior to Day -1 through study end
  • Willing to abstain from grapefruit-, pomelo-, star fruit-, or Seville orange-containing products from day 7 prior study start until study end
  • Willing to avoid prolonged sun exposure while taking alectinib and through follow-up

Exclusion Criteria:

  • Women of childbearing potential, pregnant or lactating women, or males with female partners who are pregnant or lactating
  • Clinically significant abnormalities on physical examination, vital signs, or laboratory test results during screening or prior to admission to the study center
  • Positive test for drugs of abuse, alcohol, or cotinine at screening or prior to admission to the study center or suspicion of regular consumption of drug(s) of abuse including marijuana
  • History (within 3 months of Screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams [g] of alcohol). Alcohol consuming will be prohibited from 72 hours prior to study start until the end of the study
  • Participants with any risk factors or family history for QT/Fridericia's corrected QT interval (QTcF) prolongation or electrocardiogram abnormalities
  • A history of any concurrent clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, allergies, gastrointestinal, metabolic or endocrine disorder, or cardiovascular disease or infections
  • Positive screening test for hepatitis B, C, or human immunodeficiency virus (HIV)
  • Use of any medications (prescriptions or over-the-counter), within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study drug with exception of acetaminophen up to 2 g per day up to 48 hours prior to dosing, not to exceed 4 g total during the week prior to dosing
  • Routine or chronic use of more than 2 g of acetaminophen daily
  • Use of any herbal supplements (for example, St. John's Wort) or any metabolic inducers within 4 weeks or 5 half-lives (whichever is longer) before the first dose of study drug, including but not limited to the following drugs: rifampin, rifabutin, glucocorticoids, carbamazepine, phenytoin, and phenobarbital
  • Strenuous activity, sunbathing or contact sports are not allowed from 4 days prior to study start until the end of the study
  • 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 first study drug dosing
  • Donation of blood over 450 milliliters within 45 days prior to screening

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): NCT02074553


Locations
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United States, Texas
Austin, Texas, United States, 78744
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02074553     History of Changes
Other Study ID Numbers: NP29040
First Posted: February 28, 2014    Key Record Dates
Results First Posted: October 18, 2016
Last Update Posted: October 18, 2016
Last Verified: August 2016