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Trial record 13 of 37 for:    ALECTINIB

A Study of the Effects of Posaconazole on Alectinib (RO5424802) Pharmacokinetics in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT01984229
Recruitment Status : Completed
First Posted : November 14, 2013
Results First Posted : October 11, 2016
Last Update Posted : October 11, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy Volunteer
Interventions Drug: Alectinib
Drug: Posaconazole
Enrollment 23
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort A: Alectinib 40mg, Posaconazole, Alectinib+Posaconazole Cohort B:Alectinib 300mg, Posaconazole, Alectinib+Posaconazole
Hide Arm/Group Description There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 18). Alectinib was administered as a 40 milligrams (mg) single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg twice daily (BID) oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole. There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 21). Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole.
Period Title: Period 1
Started 6 17
Completed 6 17
Not Completed 0 0
Period Title: Period 2
Started 6 17
Completed 6 17
Not Completed 0 0
Period Title: Period 3
Started 6 17
Completed 6 17
Not Completed 0 0
Period Title: Safety Follow-up Period
Started 6 17
Completed 4 16
Not Completed 2 1
Reason Not Completed
Adverse Event             1             1
Lost to Follow-up             1             0
Arm/Group Title Cohort A: Alectinib 40mg, Posaconazole, Alectinib+Posaconazole Cohort B:Alectinib 300mg, Posaconazole, Alectinib+Posaconazole Total
Hide Arm/Group Description There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 18). Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole. There were 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 21). Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments occurred within 10 to 14 days after the last dose of posaconazole. Total of all reporting groups
Overall Number of Baseline Participants 6 17 23
Hide Baseline Analysis Population Description
Safety Analysis Set consisted of all participants who received at least 1 dose of study drug and had at least 1 after dosing safety assessment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 17 participants 23 participants
37.8  (8.50) 38.5  (8.40) 38.3  (8.24)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 17 participants 23 participants
Female
2
  33.3%
2
  11.8%
4
  17.4%
Male
4
  66.7%
15
  88.2%
19
  82.6%
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A
Hide Description [Not Specified]
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Population [Cohort A] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments.
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
27.6  (6.61) 35.0  (10.8)
2.Primary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Cohort A
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort A]
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: hours*nanograms per milliliter (h*ng/mL)
634  (133) 1030  (270)
3.Primary Outcome
Title Cmax of Alectinib: Cohort B
Hide Description [Not Specified]
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B] consisted of all participants who received both scheduled doses of Alectinib, and provided adequate PK assessments.
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: ng/mL
147  (39.3) 171  (38.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort B: Alectinib (Period 1), Cohort B: Alectinib + Posaconazole (Period 3)
Comments Analysis of variance (ANOVA) was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and confidence intervals (CIs).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 118
Confidence Interval (2-Sided) 90%
102 to 137
Estimation Comments The reported values are percentages of geometric least square mean ratio.
4.Primary Outcome
Title AUClast of Alectinib: Cohort B
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
2770  (545) 4910  (893)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort B: Alectinib (Period 1), Cohort B: Alectinib + Posaconazole (Period 3)
Comments ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 177
Confidence Interval (2-Sided) 90%
159 to 198
Estimation Comments The reported values are percentages of geometric least square mean ratio.
5.Primary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of RO5424802: Cohort B
Hide Description AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
2850  (549) 4990  (888)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort B: Alectinib (Period 1), Cohort B: Alectinib + Posaconazole (Period 3)
Comments ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 175
Confidence Interval (2-Sided) 90%
157 to 195
Estimation Comments The reported values are percentages of geometric least square mean ratio.
6.Secondary Outcome
Title Cmax of RO5468924: Cohort A
Hide Description RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort A]
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: ng/mL
6.52  (1.59) 2.54  (0.296)
7.Secondary Outcome
Title AUClast of RO5468924: Cohort A
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort A]
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
138  (36.8) 65.1  (20.4)
8.Secondary Outcome
Title AUC0-inf of RO5468924: Cohort A
Hide Description AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort A]. Here, number of participants analyzed = participants who were evaluable for this outcome.
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 3
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
201  (35.9) 256  (94.5)
9.Secondary Outcome
Title Cmax of RO5468924: Cohort B
Hide Description RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: ng/mL
59.6  (27.1) 15.5  (4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort B: Alectinib (Period 1), Cohort B: Alectinib + Posaconazole (Period 3)
Comments ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 28.7
Confidence Interval (2-Sided) 90%
23.1 to 35.5
Estimation Comments The reported values are percentages of geometric least square mean ratio.
10.Secondary Outcome
Title AUClast of RO5468924: Cohort B
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
1460  (562) 910  (211)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort B: Alectinib (Period 1), Cohort B: Alectinib + Posaconazole (Period 3)
Comments ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 66.2
Confidence Interval (2-Sided) 90%
56.7 to 77.4
Estimation Comments The reported values are percentages of geometric least square mean ratio.
11.Secondary Outcome
Title AUC0-inf of RO5468924: Cohort B
Hide Description AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
1550  (569) 1110  (284)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort B: Alectinib (Period 1), Cohort B: Alectinib + Posaconazole (Period 3)
Comments ANOVA was applied to the log-transformed PK parameter and then back transformed to provide geometric least square mean ratios (Period 3/Period 1) and CIs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Square Mean Ratio
Estimated Value 75.1
Confidence Interval (2-Sided) 90%
64.4 to 87.7
Estimation Comments The reported values are percentages of geometric least square mean ratio.
12.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A
Hide Description [Not Specified]
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population [Cohort A]
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Median (Full Range)
Unit of Measure: hours
8.15
(6.00 to 12.0)
8.00
(4.00 to 11.9)
13.Secondary Outcome
Title Tmax of Alectinib: Cohort B
Hide Description [Not Specified]
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Median (Full Range)
Unit of Measure: hours
8.00
(6.00 to 12.0)
8.00
(6.00 to 11.9)
14.Secondary Outcome
Title Tmax of RO5468924: Cohort A
Hide Description RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population [Cohort A]
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Median (Full Range)
Unit of Measure: hours
12.0
(6.03 to 12.0)
11.9
(6.00 to 11.9)
15.Secondary Outcome
Title Tmax of RO5468924: Cohort B
Hide Description RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Median (Full Range)
Unit of Measure: hours
12.0
(6.00 to 12.0)
11.9
(6.00 to 12.0)
16.Secondary Outcome
Title Metabolite/Parent Ratio for AUC0-inf: Cohort B
Hide Description AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf). RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
0.541  (0.12) 0.232  (0.02)
17.Secondary Outcome
Title Metabolite/Parent Ratio for Cmax: Cohort B
Hide Description RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Standard Deviation)
Unit of Measure: ratio
0.393  (0.10) 0.0953  (0.01)
18.Secondary Outcome
Title Terminal Half-life (t1/2) of Alectinib: Cohort A
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population [Cohort A]
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: hours
19.6  (2.37) 26.9  (3.22)
19.Secondary Outcome
Title t1/2 of Alectinib: Cohort B
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: hours
18.4  (4.36) 24.8  (5.08)
20.Secondary Outcome
Title t1/2 of RO5468924: Cohort A
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period
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Hide Analysis Population Description
PK analysis population [Cohort A]. Here, number of participants analyzed = participants who were evaluable for this outcome.
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 5 3
Mean (Standard Deviation)
Unit of Measure: hours
23.9  (9.92) 79.6  (47.2)
21.Secondary Outcome
Title t1/2 of RO5468924: Cohort B
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of Alectinib.
Time Frame Predose (0 hours) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing in each treatment period, and additional samples were collected in Period 3 at 120, 144, 168, 192, and 216 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Population [Cohort B]
Arm/Group Title Cohort B: Alectinib (Period 1) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description:
Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1).
Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: hours
25.3  (4.12) 69.6  (22.7)
Time Frame Day 1 up to 10 to 14 days after last dose of posaconazole (Cohort A: maximum up to 28 to 32 days; Cohort B: maximum up to 31 to 35 days)
Adverse Event Reporting Description Safety Analysis Set. Only 5 participants were evaluable for adverse events in Cohort A: Alectinib + Posaconazole (Period 3) arm.
 
Arm/Group Title Cohort A: Alectinib (Period 1) Cohort A: Posaconazole (Period 2) Cohort A: Alectinib + Posaconazole (Period 3) Cohort B: Alectinib (Period 1) Cohort B: Posaconazole (Period 2) Cohort B: Alectinib + Posaconazole (Period 3)
Hide Arm/Group Description Alectinib was administered as a 40-mg single oral dose on Day 1 (Period 1). Posaconazole was administered as a 400-mg BID oral dose on Days 8 to 14 (Period 2) after a high-fat meal. Alectinib was administered as a 40-mg single oral dose on Day 15 (Period 3). On Days 15 to 18 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal. Alectinib was administered as a 300-mg single oral dose on Day 1 (Period 1). Posaconazole was administered as a 400-mg BID oral dose on Days 8 to 14 (Period 2) after a high-fat meal. Alectinib was administered as a 300-mg single oral dose on Day 15 (Period 3). On Days 15 to 21 (Period 3) posaconazole was administered as a 400-mg BID oral dose after a high-fat meal.
All-Cause Mortality
Cohort A: Alectinib (Period 1) Cohort A: Posaconazole (Period 2) Cohort A: Alectinib + Posaconazole (Period 3) Cohort B: Alectinib (Period 1) Cohort B: Posaconazole (Period 2) Cohort B: Alectinib + Posaconazole (Period 3)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort A: Alectinib (Period 1) Cohort A: Posaconazole (Period 2) Cohort A: Alectinib + Posaconazole (Period 3) Cohort B: Alectinib (Period 1) Cohort B: Posaconazole (Period 2) Cohort B: Alectinib + Posaconazole (Period 3)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/5 (0.00%)   0/17 (0.00%)   0/17 (0.00%)   0/17 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort A: Alectinib (Period 1) Cohort A: Posaconazole (Period 2) Cohort A: Alectinib + Posaconazole (Period 3) Cohort B: Alectinib (Period 1) Cohort B: Posaconazole (Period 2) Cohort B: Alectinib + Posaconazole (Period 3)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   3/6 (50.00%)   2/5 (40.00%)   3/17 (17.65%)   4/17 (23.53%)   5/17 (29.41%) 
Gastrointestinal disorders             
Abdominal distension * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/17 (0.00%) 
Abdominal pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/17 (5.88%)  2/17 (11.76%)  0/17 (0.00%) 
Change of bowel habit * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
Chapped lips * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
Diarrhoea * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/17 (5.88%)  2/17 (11.76%)  0/17 (0.00%) 
Dysphagia * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
General disorders             
Influenza like illness * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
Nodule * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  0/17 (0.00%) 
Infections and infestations             
Hordeolum * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/17 (0.00%) 
Nasopharyngitis * 1  0/6 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/17 (5.88%)  0/17 (0.00%)  0/17 (0.00%) 
Tooth abscess * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  0/17 (0.00%) 
Injury, poisoning and procedural complications             
Tooth fracture * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  0/17 (0.00%) 
Investigations             
Blood creatine phosphokinase increase * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  0/6 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/17 (5.88%)  0/17 (0.00%)  0/17 (0.00%) 
Back pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  1/17 (5.88%) 
Bone pain * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  0/17 (0.00%) 
Neck pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
Nervous system disorders             
Somnolence * 1  0/6 (0.00%)  2/6 (33.33%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  0/17 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Epistaxis * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/17 (0.00%) 
Skin and subcutaneous tissue disorders             
Acne * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/17 (0.00%) 
Dermal cyst * 1  0/6 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/17 (0.00%)  0/17 (0.00%)  0/17 (0.00%) 
Rash maculo-papular * 1  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/17 (0.00%)  0/17 (0.00%)  1/17 (5.88%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01984229     History of Changes
Other Study ID Numbers: NP28990
First Submitted: November 7, 2013
First Posted: November 14, 2013
Results First Submitted: August 16, 2016
Results First Posted: October 11, 2016
Last Update Posted: October 11, 2016