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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01984229
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 7.8

Study Details

Study Description

Brief Summary

This open-label study will investigate whether multiple oral doses of posaconazole affect the single dose pharmacokinetics of alectinib in healthy volunteers.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteer	Drug: Alectinib; Drug: Posaconazole	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Three-Period, Fixed Sequence Study to Investigate the Effect of Multiple Oral Doses of Posaconazole, a Potent Cytochrome P450 3A Inhibitor, on the Single Dose Pharmacokinetics of RO5424802 in Healthy Subjects
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A There will be 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 will be 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 will be administered as a 400-mg twice daily (BID) oral dose after a high-fat meal. The follow-up assessments will occur within 10 to 14 days after the last dose of posaconazole.	Drug: Alectinib; Alectinib will be administered as a 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).; Other Names: RO5424802 ; Drug: Posaconazole; Posaconazole will be administered as a 400-mg BID oral dose after a high-fat meal on Days 8 to 14 (Period 2) and Days 15 to 18 or 21 (Period 3).
Experimental: Cohort B There will be 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 will be administered as a single oral dose at the dose selected based on Cohort A data 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 will be administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments will occur within 10 to 14 days after the last dose of posaconazole.	Drug: Alectinib; Alectinib will be administered as a 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).; Other Names: RO5424802 ; Drug: Posaconazole; Posaconazole will be administered as a 400-mg BID oral dose after a high-fat meal on Days 8 to 14 (Period 2) and Days 15 to 18 or 21 (Period 3).

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A [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]

2. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Alectinib: Cohort A [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]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

3. Cmax of Alectinib: Cohort B [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]

4. AUClast of Alectinib: Cohort B [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]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

5. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of RO5424802: Cohort B [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]

   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).

Secondary Outcome Measures

1. Cmax of RO5468924: Cohort A [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]

   RO5468924 is M4 metabolite of Alectinib.

2. AUClast of RO5468924: Cohort A [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]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib.

3. AUC0-inf of RO5468924: Cohort A [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]

   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.

4. Cmax of RO5468924: Cohort B [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]

   RO5468924 is M4 metabolite of Alectinib.

5. AUClast of RO5468924: Cohort B [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]

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). RO5468924 is M4 metabolite of Alectinib.

6. AUC0-inf of RO5468924: Cohort B [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]

   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.

7. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib: Cohort A [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]

8. Tmax of Alectinib: Cohort B [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]

9. Tmax of RO5468924: Cohort A [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]

   RO5468924 is M4 metabolite of Alectinib.

10. Tmax of RO5468924: Cohort B [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]

    RO5468924 is M4 metabolite of Alectinib.

11. Metabolite/Parent Ratio for AUC0-inf: Cohort B [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]

    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.

12. Metabolite/Parent Ratio for Cmax: Cohort B [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]

    RO5468924 is M4 metabolite of Alectinib. The ratio is molecular weight adjusted.

13. Terminal Half-life (t1/2) of Alectinib: Cohort A [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]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

14. t1/2 of Alectinib: Cohort B [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]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

15. t1/2 of RO5468924: Cohort A [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]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of Alectinib.

16. t1/2 of RO5468924: Cohort B [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]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. RO5468924 is M4 metabolite of Alectinib.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Body mass index (BMI) between 18 to 32 kilogram per square meter (kg/m^2)

• Male volunteers must use effective contraception as outlined in the protocol

• Willingness to abstain from alcohol and xanthine-containing beverages or food (coffee, tea, cola, chocolate and "energy drinks") from 72 hours prior to the first dose until discharged

• Willingness to avoid prolonged sun exposure and guard against sunburn during study and follow-up

Exclusion Criteria:

• Clinically significant medical history or findings in physical examination, vital signs, or laboratory test results prior to study start

• Positive screening tests for hepatitis B or C, human immunodeficiency virus (HIV), alcohol, drugs of abuse, or tobacco

• Women of childbearing potential, or males with pregnant or lactating partners

• Regular smoking within 6 months prior to first dosing. Participants should avoid smoky environments for at least 1 week prior to each cotinine screen

• Excessive alcohol consumption

• Use of any metabolic inducers (including herbals such as St. John's Wort) within 4 weeks or 5 half-lives (whichever is longer) before the first dose of study medication, including but not limited to: rifampin, rifabutin, glucocorticoids, carbamazepine, phenytoin and phenobarbital

• Strenuous activity, sunbathing, or contact sports are not allowed from 4 days prior to entry into the clinical site until study follow-up

• Participation in an investigational drug or device study within 45 days (or 6 months for biologic therapies) prior to first dosing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States	78744

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01984229
• Other Study ID Numbers: NP28990
• First Posted: Nov 14, 2013
• Last Update Posted: Oct 11, 2016
• Last Verified: Aug 1, 2016

• Additional relevant MeSH terms: Posaconazole

Study Results

Participant Flow

Arm/Group Title	Cohort A: Alectinib 40mg, Posaconazole, Alectinib+Posaconazole	Cohort B:Alectinib 300mg, Posaconazole, Alectinib+Posaconazole
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 1
STARTED	6	17
COMPLETED	6	17
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	6	17
COMPLETED	6	17
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	6	17
COMPLETED	4	16
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Cohort A: Alectinib 40mg, Posaconazole, Alectinib+Posaconazole	Cohort B:Alectinib 300mg, Posaconazole, Alectinib+Posaconazole	Total
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 Participants	6	17	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.8 (8.50)	38.5 (8.40)	38.3 (8.24)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	2 11.8%	4 17.4%
Male	4 66.7%	15 88.2%	19 82.6%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Alectinib: Cohort A
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

Outcome Measure Data

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)
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.
Measure Participants	5	5
Mean (Standard Deviation) [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
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort A]

Arm/Group Title	Cohort A: Alectinib (Period 1)	Cohort A: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	5	5
Mean (Standard Deviation) [hours*nanograms per milliliter (h*ng/mL)]	634 (133)	1030 (270)

3. Primary Outcome

Title	Cmax of Alectinib: Cohort B
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

Outcome Measure Data

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)
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.
Measure Participants	16	16
Mean (Standard Deviation) [ng/mL]	147 (39.3)	171 (38.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Alectinib (Period 1), Cohort A: 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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	118
	Confidence Interval	(2-Sided) 90%; 102 to 137
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

4. Primary Outcome

Title	AUClast of Alectinib: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [h*ng/mL]	2770 (545)	4910 (893)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Alectinib (Period 1), Cohort A: 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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	177
	Confidence Interval	(2-Sided) 90%; 159 to 198
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [h*ng/mL]	2850 (549)	4990 (888)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Alectinib (Period 1), Cohort A: 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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	175
	Confidence Interval	(2-Sided) 90%; 157 to 195
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

6. Secondary Outcome

Title	Cmax of RO5468924: Cohort A
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort A]

Arm/Group Title	Cohort A: Alectinib (Period 1)	Cohort A: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	5	5
Mean (Standard Deviation) [ng/mL]	6.52 (1.59)	2.54 (0.296)

7. Secondary Outcome

Title	AUClast of RO5468924: Cohort A
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort A]

Arm/Group Title	Cohort A: Alectinib (Period 1)	Cohort A: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	5	5
Mean (Standard Deviation) [h*ng/mL]	138 (36.8)	65.1 (20.4)

8. Secondary Outcome

Title	AUC0-inf of RO5468924: Cohort A
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

Outcome Measure Data

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)
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.
Measure Participants	5	3
Mean (Standard Deviation) [h*ng/mL]	201 (35.9)	256 (94.5)

9. Secondary Outcome

Title	Cmax of RO5468924: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [ng/mL]	59.6 (27.1)	15.5 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Alectinib (Period 1), Cohort A: 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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	28.7
	Confidence Interval	(2-Sided) 90%; 23.1 to 35.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

10. Secondary Outcome

Title	AUClast of RO5468924: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [h*ng/mL]	1460 (562)	910 (211)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Alectinib (Period 1), Cohort A: 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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	66.2
	Confidence Interval	(2-Sided) 90%; 56.7 to 77.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The reported values are percentages of geometric least square mean ratio.

11. Secondary Outcome

Title	AUC0-inf of RO5468924: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [h*ng/mL]	1550 (569)	1110 (284)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A: Alectinib (Period 1), Cohort A: 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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Square Mean Ratio
	Estimated Value	75.1
	Confidence Interval	(2-Sided) 90%; 64.4 to 87.7
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description

PK analysis population [Cohort A]

Arm/Group Title	Cohort A: Alectinib (Period 1)	Cohort A: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	5	5
Median (Full Range) [hours]	8.15	8.00

13. Secondary Outcome

Title	Tmax of Alectinib: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Median (Full Range) [hours]	8.00	8.00

14. Secondary Outcome

Title	Tmax of RO5468924: Cohort A
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

Outcome Measure Data

Analysis Population Description

PK analysis population [Cohort A]

Arm/Group Title	Cohort A: Alectinib (Period 1)	Cohort A: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	5	5
Median (Full Range) [hours]	12.0	11.9

15. Secondary Outcome

Title	Tmax of RO5468924: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Median (Full Range) [hours]	12.0	11.9

16. Secondary Outcome

Title	Metabolite/Parent Ratio for AUC0-inf: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Geometric Mean (Standard Deviation) [ratio]	0.541 (0.12)	0.232 (0.02)

17. Secondary Outcome

Title	Metabolite/Parent Ratio for Cmax: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Geometric Mean (Standard Deviation) [ratio]	0.393 (0.10)	0.0953 (0.01)

18. Secondary Outcome

Title	Terminal Half-life (t1/2) of Alectinib: Cohort A
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

Outcome Measure Data

Analysis Population Description

PK analysis population [Cohort A]

Arm/Group Title	Cohort A: Alectinib (Period 1)	Cohort A: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	5	5
Mean (Standard Deviation) [hours]	19.6 (2.37)	26.9 (3.22)

19. Secondary Outcome

Title	t1/2 of Alectinib: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [hours]	18.4 (4.36)	24.8 (5.08)

20. Secondary Outcome

Title	t1/2 of RO5468924: Cohort A
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

Outcome Measure Data

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)
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.
Measure Participants	5	3
Mean (Standard Deviation) [hours]	23.9 (9.92)	79.6 (47.2)

21. Secondary Outcome

Title	t1/2 of RO5468924: Cohort B
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

Outcome Measure Data

Analysis Population Description

PK Analysis Population [Cohort B]

Arm/Group Title	Cohort B: Alectinib (Period 1)	Cohort B: Alectinib + Posaconazole (Period 3)
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.
Measure Participants	16	16
Mean (Standard Deviation) [hours]	25.3 (4.12)	69.6 (22.7)

Adverse Events

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)
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Other (Not Including 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		3/6 (50%)		2/5 (40%)		3/17 (17.6%)		4/17 (23.5%)		5/17 (29.4%)
Gastrointestinal disorders
Abdominal distension	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		1/17 (5.9%)		0/17 (0%)
Abdominal pain	0/6 (0%)		0/6 (0%)		0/5 (0%)		1/17 (5.9%)		2/17 (11.8%)		0/17 (0%)
Change of bowel habit	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)
Chapped lips	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)
Diarrhoea	0/6 (0%)		0/6 (0%)		0/5 (0%)		1/17 (5.9%)		2/17 (11.8%)		0/17 (0%)
Dysphagia	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)
General disorders
Influenza like illness	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)
Nodule	0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Infections and infestations
Hordeolum	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		1/17 (5.9%)		0/17 (0%)
Nasopharyngitis	0/6 (0%)		0/6 (0%)		1/5 (20%)		1/17 (5.9%)		0/17 (0%)		0/17 (0%)
Tooth abscess	0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Injury, poisoning and procedural complications
Tooth fracture	0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Investigations
Blood creatine phosphokinase increase	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/6 (0%)		0/6 (0%)		1/5 (20%)		1/17 (5.9%)		0/17 (0%)		0/17 (0%)
Back pain	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		1/17 (5.9%)		1/17 (5.9%)
Bone pain	0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Neck pain	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)
Nervous system disorders
Somnolence	0/6 (0%)		2/6 (33.3%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		1/17 (5.9%)		0/17 (0%)
Skin and subcutaneous tissue disorders
Acne	0/6 (0%)		1/6 (16.7%)		0/5 (0%)		0/17 (0%)		1/17 (5.9%)		0/17 (0%)
Dermal cyst	0/6 (0%)		0/6 (0%)		1/5 (20%)		0/17 (0%)		0/17 (0%)		0/17 (0%)
Rash maculo-papular	0/6 (0%)		0/6 (0%)		0/5 (0%)		0/17 (0%)		0/17 (0%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.