A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01871805
• Collaborator: (none)
• Enrollment: 134
• Locations: 42
• Arms: 2
• Actual Duration (Months): 47
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of alectinib in participants with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Alectinib	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of the ALK Inhibitor CH5424802/ RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer Previously Treated With Crizotinib
• Actual Study Start Date: Sep 30, 2013
• Actual Primary Completion Date: Oct 24, 2014
• Actual Study Completion Date: Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alectinib: Phase I (Dose Escalation) Participants will receive escalating doses of alectinib capsules orally until disease progression, death or withdrawal for any other reasons.	Drug: Alectinib; Participants will receive alectinib as described in the arm descriptions.; Other Names: CH5424802 RO5424802
Experimental: Alectinib (Phase II: RP2 dose) Participants will receive recommended Phase II dose as determined from Phase I until disease progression, death or withdrawal for any other reasons.	Drug: Alectinib; Participants will receive alectinib as described in the arm descriptions.; Other Names: CH5424802 RO5424802

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities (DLTs): Phase I [Throughout Cycle 1 of Phase I (21 days)]

   The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of >=7 days which the Investigator could not rule out as been related to alectinib.

2. Recommended Phase II Dose (RP2D): Phase I [Throughout Cycle 1 of Phase I (21 days)]

   RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.

3. Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II [Cycle 1 Day 1 up to 194 weeks (assessed at every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter) (1 cycle = 21 days)]

   Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).

Secondary Outcome Measures

1. Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.

2. Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.

3. Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI.

4. Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   Disease control rate assessed according to RECIST v1.1 was defined as the percentage of participants with a best overall response of CR, PR, or stable disease (SD) lasting for at least 12 weeks, after the first dose of alectinib. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. 95% CI for rate was constructed using Clopper-Pearson method.

5. Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   Percentage of participants with disease progression according to RECIST v1.1 by IRC is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.

6. Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

7. Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   Percentage of participants with disease progression according to RECIST v1.1 by investigator is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.

8. PFS According to RECIST v1.1 by Investigator: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

   PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

9. Percentage of Participants Who Died Due to Any Cause: Phase II [Baseline up to death (any cause) (maximum follow up 284 weeks)]

10. Overall Survival (OS) Time: Phase II [Baseline up to death (any cause) (maximum follow up 284 weeks)]

    OS was defined as the time between date of first dose and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants without any follow-up information were censored at the date of first dose. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

11. DOR According to RECIST v1.1 by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

12. DOR According to RECIST v1.1 by Investigator: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

13. Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    COR rate (CORR) was defined as the percentage of participants who had a CR or PR of the baseline central nervous system (CNS) lesions, based on RECIST v.1.1. CNS responses according to RECIST v1.1 did not have to be confirmed. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). 95% CI was computed using the Clopper-Pearson method.

14. Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    CORR was defined as the percentage of participants who had a CR or PR according to RANO criteria of the baseline CNS lesions. As per RANO criteria, CR was defined as disappearance of all enhancing measurable and non-measurable disease, and no new lesions along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and stable or improved non enhancing T2/FLAIR lesions; PR was defined as 50% or more decrease in sum of the products of the diameters (SPD) of measurable enhancing measurable lesions, no new lesion along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and no progression of non-measurable disease (enhancing and non-enhancing T2/FLAIR lesions. Clopper-Pearson method was used to calculate 95% CI.

15. CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    CDOR was defined for CNS responders as the time from the first observation of a CNS response of CR or PR until first observation of CNS progression or death from any cause. An analysis by IRC using RECIST v1.1 was performed. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

16. CDOR According to RANO Criteria by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    CDOR was defined as the time from the first observation of a CNS response of CR or PR according to RANO criteria until first observation of CNS progression or death from any cause. An analysis by RANO criteria was performed. Definitions of CR or PR as per RANO was included in description of Outcome Measure 17. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease) and clear worsening of neurological status with respect to the previous timepoint. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.

17. Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RECIST v1.1. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.

18. Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II [Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)]

    CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RANO criteria. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).

19. Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I [Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)]

20. Cmax After Multiple Dose of Alectinib: Phase I [Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)]

21. Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I [Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)]

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

22. AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I [Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)]

23. Ctrough After Multiple Dose of Alectinib: Phase II [Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 (1 cycle = 21 days)]

24. Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II [Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)]

    EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to lie between 0-100 scale; for each of the symptom scales, higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below (e.g. Global health status/QoL [quality of life]) represents absolute data at baseline. QoL=quality of life

25. Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II [Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)]

    EORTC QLQ-LC13 consisted of 13 questions for dyspnea (3 items) and 10 single items (cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm/shoulder, other pain). Questions used 4-point scale (1 'Not at all' to 4 'Very much'). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below represents absolute data at baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic NSCLC

• ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test

• NSCLC that has failed crizotinib treatment

• Measurable disease as defined by RECIST v1.1

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2

• Adequate hematologic, hepatic and renal function

Exclusion Criteria:

• Prior therapy with ALK inhibitor other than crizotinib

• Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment

• History of serious cardiac dysfunction

• History of or current active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)

• Clinically significant gastrointestinal abnormality that would affect absorption of the drug

• Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of California Irvine	Irvine	California	United States	92697
3	UCSD Moores Cancer Center	La Jolla	California	United States	92093
4	Loma Linda Cancer Center	Loma Linda	California	United States	92354
5	UCLA	Los Angeles	California	United States	90095
6	Univ of Colorado Canc Ctr	Aurora	Colorado	United States	80045
7	National Jewish Health	Denver	Colorado	United States	80206
8	Lynn Regional Cancer Center West	Boca Raton	Florida	United States	33486
9	Florida Hospital Cancer Inst	Orlando	Florida	United States	32804
10	UF Health Orlando	Orlando	Florida	United States	32806
11	H. Lee Moffitt Cancer Center and Research Inst.	Tampa	Florida	United States	33612
12	University of Illinois Cancer Center	Chicago	Illinois	United States	60612
13	Monroe Medical Associates; Ingalls Memorial Hosp	Harvey	Illinois	United States	60426
14	Massachussets General Hospital	Boston	Massachusetts	United States	02114
15	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
16	Dana Farber Can Ins	Boston	Massachusetts	United States	02215
17	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
18	St. Joseph Mercy Hospital; Cancer Care Center.	Ann Arbor	Michigan	United States	48106
19	Wayne State Uni ; Karmanos Cancer Center	Detroit	Michigan	United States	48201
20	Hackensack Univ Med Ctr	Hackensack	New Jersey	United States	07601
21	Roswell Park Cancer Inst.	Buffalo	New York	United States	14263
22	Memorial Sloan-Kettering Cancer Center	Commack	New York	United States	11725
23	Richmond University Medical Center; Pharmacy Department	Staten Island	New York	United States	10310
24	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
25	Gabrail Cancer Center	Canton	Ohio	United States	44718
26	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
27	Providence Portland Med Ctr	Portland	Oregon	United States	97213
28	Oregon Health & Science Uni	Portland	Oregon	United States	97239
29	St. Luke's Hospital; Pharmacy Department	Bethlehem	Pennsylvania	United States	18015
30	Penn State Hershey Cancer Institute	Hershey	Pennsylvania	United States	17033
31	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
32	University of Pittsburgh Cancer Pavillion	Pittsburgh	Pennsylvania	United States	15232
33	MUSC Hollings Cancer Center	Charleston	South Carolina	United States	29425
34	Center for Biomedical Research LLC	Knoxville	Tennessee	United States	37909
35	Texas Oncology-Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
36	MD Anderson Cancer Center	Houston	Texas	United States	77030
37	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
38	Swedish Cancer Inst.	Seattle	Washington	United States	98104
39	University of Wisconsin	Madison	Wisconsin	United States	53792
40	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
41	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario	Canada	L1G 2B9
42	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec	Canada	H3T 1E2

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: NCT01871805
• Other Study ID Numbers: NP28761; NCT01588028
• First Posted: Jun 7, 2013
• Last Update Posted: Aug 21, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40/150 mg)	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received single dose of 20 or 40 milligrams (mg) alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg twice daily (BID) dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received 150 mg alectinib capsules orally to make a dose of 600 mg BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Period Title: Phase I
STARTED	7	7	13	7	13	0
COMPLETED	0	0	0	0	0	0
NOT COMPLETED	7	7	13	7	13	0
Period Title: Phase I
STARTED	0	0	0	0	0	87
COMPLETED	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	87

Baseline Characteristics

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40/150 mg)	Alectinib 600 mg (Fed): Phase II	Total
Arm/Group Description	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Total of all reporting groups
Overall Participants	7	7	13	7	13	87	134
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 100%	6 85.7%	12 92.3%	7 100%	10 76.9%	71 81.6%	113 84.3%
>=65 years	0 0%	1 14.3%	1 7.7%	0 0%	3 23.1%	16 18.4%	21 15.7%
Sex: Female, Male (Count of Participants)
Female	2 28.6%	4 57.1%	3 23.1%	2 28.6%	9 69.2%	48 55.2%	68 50.7%
Male	5 71.4%	3 42.9%	10 76.9%	5 71.4%	4 30.8%	39 44.8%	66 49.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs): Phase I
Description	The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of >=7 days which the Investigator could not rule out as been related to alectinib.
Time Frame	Throughout Cycle 1 of Phase I (21 days)

Outcome Measure Data

Analysis Population Description

Phase I safety population

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40/150 mg)
Arm/Group Description	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	7	7	13	7	13
Number [participants]	0 0%	0 0%	0 0%	0 0%	2 15.4%

2. Primary Outcome

Title	Recommended Phase II Dose (RP2D): Phase I
Description	RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.
Time Frame	Throughout Cycle 1 of Phase I (21 days)

Outcome Measure Data

Analysis Population Description

Phase I safety population

Arm/Group Title	Alectinib: Phase I
Arm/Group Description	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 240, 300, 460, 600, 760, or 900 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	47
Number [mg]	600

3. Primary Outcome

Title	Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II
Description	Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).
Time Frame	Cycle 1 Day 1 up to 194 weeks (assessed at every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II Response evaluable (RE) population comprised all Phase II participants with measurable disease at baseline who had a baseline tumor assessment and received at least one dose of alectinib.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	67
Number (95% Confidence Interval) [percentage of participants]	52.2 745.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib 300 mg (Fasted): Phase I
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0056
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I
Description	Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I RE population comprised all Phase I participants with measurable disease at baseline who had a baseline tumor assessment and received at least one dose of alectinib.

Arm/Group Title	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib Other Than 600 mg (Fasted/Fed): Phase I
Arm/Group Description	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 240, 300, 460, 760, or 900 mg on Cycle 1 Day -3 and then received 300, 460, 760, or 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	13	34
Number (95% Confidence Interval) [percentage of participants]	69.2 988.6%	55.9 798.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib 300 mg (Fasted): Phase I
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0251
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib 460 mg (Fed): Phase I
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0203
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments

5. Secondary Outcome

Title	Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I
Description	DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI. Data for this outcome were reported for 'alectinib 600 mg' and 'alectinib other than 600 mg' groups as planned.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I RE population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase I (20/40/150 mg)	Alectinib Other Than 600 mg (Fasted/Fed): Phase I
Arm/Group Description	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 240, 300, 460, 760, or 900 mg on Cycle 1 Day -3 and then received 300, 460, 760, or 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	9	19
Median (95% Confidence Interval) [months]	12.2	11.0

6. Secondary Outcome

Title	Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II
Description	Percentage of participants with objective response as assessed by Investigator was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments >=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Number (95% Confidence Interval) [percentage of participants]	52.9 755.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib 300 mg (Fasted): Phase I
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	Tests null hypothesis that the response rate is equal to 35% versus the alternative hypothesis that the response rate is not equal to 35%.
	Method	Exact Clopper-Pearson CI, 2 sided
	Comments

7. Secondary Outcome

Title	Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II
Description	Disease control rate assessed according to RECIST v1.1 was defined as the percentage of participants with a best overall response of CR, PR, or stable disease (SD) lasting for at least 12 weeks, after the first dose of alectinib. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. 95% CI for rate was constructed using Clopper-Pearson method.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Number (95% Confidence Interval) [percentage of participants]	66.7 952.9%

8. Secondary Outcome

Title	Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II
Description	Percentage of participants with disease progression according to RECIST v1.1 by IRC is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Number [percentage of participants]	66.7 952.9%

9. Secondary Outcome

Title	Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II
Description	PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Median (95% Confidence Interval) [months]	8.2

10. Secondary Outcome

Title	Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II
Description	Percentage of participants with disease progression according to RECIST v1.1 by investigator is defined as the participants with at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Number [percentage of participants]	70.1 1001.4%

11. Secondary Outcome

Title	PFS According to RECIST v1.1 by Investigator: Phase II
Description	PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST v1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Median (95% Confidence Interval) [months]	8.4

12. Secondary Outcome

Title	Percentage of Participants Who Died Due to Any Cause: Phase II
Time Frame	Baseline up to death (any cause) (maximum follow up 284 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Number [percentage of participants]	51.7 738.6%

13. Secondary Outcome

Title	Overall Survival (OS) Time: Phase II
Description	OS was defined as the time between date of first dose and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants without any follow-up information were censored at the date of first dose. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Baseline up to death (any cause) (maximum follow up 284 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	87
Median (95% Confidence Interval) [months]	27.9

14. Secondary Outcome

Title	DOR According to RECIST v1.1 by IRC: Phase II
Description	DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	35
Median (95% Confidence Interval) [months]	14.9

15. Secondary Outcome

Title	DOR According to RECIST v1.1 by Investigator: Phase II
Description	DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST v1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a response were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II RE population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	46
Median (95% Confidence Interval) [months]	13.3

16. Secondary Outcome

Title	Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II
Description	COR rate (CORR) was defined as the percentage of participants who had a CR or PR of the baseline central nervous system (CNS) lesions, based on RECIST v.1.1. CNS responses according to RECIST v1.1 did not have to be confirmed. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). 95% CI was computed using the Clopper-Pearson method.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants with measurable CNS lesions at baseline based on RECIST v1.1 according to IRC.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	75.0 1071.4%

17. Secondary Outcome

Title	Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II
Description	CORR was defined as the percentage of participants who had a CR or PR according to RANO criteria of the baseline CNS lesions. As per RANO criteria, CR was defined as disappearance of all enhancing measurable and non-measurable disease, and no new lesions along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and stable or improved non enhancing T2/FLAIR lesions; PR was defined as 50% or more decrease in sum of the products of the diameters (SPD) of measurable enhancing measurable lesions, no new lesion along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and no progression of non-measurable disease (enhancing and non-enhancing T2/FLAIR lesions. Clopper-Pearson method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants with measurable CNS lesions at baseline according to RANO criteria by IRC.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	11
Number (95% Confidence Interval) [percentage of participants]	54.5 778.6%

18. Secondary Outcome

Title	CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II
Description	CDOR was defined for CNS responders as the time from the first observation of a CNS response of CR or PR until first observation of CNS progression or death from any cause. An analysis by IRC using RECIST v1.1 was performed. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, or presence of new lesions. CR was defined as disappearance of all CNS lesions. PR was defined as >=30% decrease in the sum of diameters of measurable CNS lesions (taking as reference the baseline sum of diameters). The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	12
Median (95% Confidence Interval) [months]	11.1

19. Secondary Outcome

Title	CDOR According to RANO Criteria by IRC: Phase II
Description	CDOR was defined as the time from the first observation of a CNS response of CR or PR according to RANO criteria until first observation of CNS progression or death from any cause. An analysis by RANO criteria was performed. Definitions of CR or PR as per RANO was included in description of Outcome Measure 17. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease) and clear worsening of neurological status with respect to the previous timepoint. The median time to the event was estimated using the methodology of Kaplan-Meier. Brookmeyer-Crowley method was used to calculate 95% CI.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	6
Median (95% Confidence Interval) [months]	12.1

20. Secondary Outcome

Title	Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II
Description	CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RECIST v1.1. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	16
Number (95% Confidence Interval) [percentage of participants]	0 0%

21. Secondary Outcome

Title	Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II
Description	CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RANO criteria. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).
Time Frame	Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Data were not estimable due to low number of responders and longer observation time.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	0

22. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I pharmacokinetic (PK) evaluable population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 240 mg Once and 300 mg BID (Fasted): Phase I	Alectinib 240 mg Once and 300 mg BID (Fed): Phase I	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description	Participants (in fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants (in non-fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	3	1	3	7	6	6	7	7	6
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	73.5 (12.4)	87.7	45.3 (9.24)	142.00 (71.4)	158.0 (67.2)	186.0 (43.1)	257.0 (83.1)	186.0 (120.0)	295.0 (131.0)

23. Secondary Outcome

Title	Cmax After Multiple Dose of Alectinib: Phase I
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	6	7	5	6	5	7	4
Mean (Standard Deviation) [ng/mL]	259 (79.0)	618 (165)	765 (176)	670 (360)	733 (98.0)	1140 (448)	1200 (311)

24. Secondary Outcome

Title	Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I
Description	AUCinf = AUC from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0- t) plus AUC (t-inf).
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 240 mg Once and 300 mg BID (Fasted): Phase I	Alectinib 240 mg Once and 300 mg BID (Fed): Phase I	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description	Participants (in fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants (in non-fasting condition) received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	3	1	3	7	6	6	7	7	6
Mean (Standard Deviation) [hour*ng/mL]	1360 (436)	858	1030 (481)	3280 (2240)	3310 (1110)	3190 (1510)	4090 (1680)	3730 (2310)	7790 (6210)

25. Secondary Outcome

Title	AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I
Time Frame	Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase I PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Alectinib 300 mg (Fasted): Phase I	Alectinib 460 mg (Fed): Phase I	Alectinib 600 mg (Fed): Phase I (20/40 mg)	Alectinib 600 mg (Fed): Phase I (150 mg)	Alectinib 760 mg (Fed): Phase I	Alectinib 900 mg (Fed): Phase I (20/40 mg)	Alectinib 900 mg (Fed): Phase I (150 mg)
Arm/Group Description	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.	Participants received single dose of 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	6	7	5	6	5	7	4
Mean (Standard Deviation) [hour*ng/mL]	1800 (562)	4510 (1700)	5970 (1140)	5300 (3180)	5780 (1020)	9800 (4660)	9500 (2670)

26. Secondary Outcome

Title	Ctrough After Multiple Dose of Alectinib: Phase II
Time Frame	Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 (1 cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Phase II PK evaluable population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specified timepoint.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	61
Cycle 2 Day 1	473 (277)
Cycle 3 Day 1	521 (272)
Cycle 4 Day 1	538 (279)
Cycle 5 Day 1	538 (226)

27. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II
Description	EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to lie between 0-100 scale; for each of the symptom scales, higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below (e.g. Global health status/QoL [quality of life]) represents absolute data at baseline. QoL=quality of life
Time Frame	Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specified timepoint.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	79
Global health status/QoL: Baseline	53.59 (24.27)
Global health status/QoL: Week 6	15.89 (25.66)
Global health status/QoL: Week 9	0.00
Global health status/QoL: Week 12	18.83 (23.41)
Global health status/QoL: Week 15	0.00
Global health status/QoL: Week 18	15.65 (23.73)
Global health status/QoL: Week 21	0.00
Global health status/QoL: Week 24	15.65 (20.77)
Global health status/QoL: Week 27	0.00 (0.00)
Global health status/QoL: Week 30	13.03 (19.57)
Global health status/QoL: Week 33	-5.56 (9.62)
Global health status/QoL: Week 36	12.28 (20.57)
Global health status/QoL: Week 39	4.17 (5.89)
Global health status/QoL: Week 42	10.19 (19.33)
Global health status/QoL: Week 45	-10.42 (12.50)
Global health status/QoL: Week 48	11.11 (19.06)
Global health status/QoL: Week 51	12.50 (17.68)
Global health status/QoL: Week 54	9.95 (16.86)
Global health status/QoL: Week 57	-3.33 (21.73)
Global health status/QoL: Week 60	10.28 (19.54)
Global health status/QoL: Week 63	11.11 (19.25)
Global health status/QoL: Week 66	15.06 (17.80)
Global health status/QoL: Week 69	12.50 (15.96)
Global health status/QoL: Week 72	8.33 (18.12)
Global health status/QoL: Week 75	16.67 (23.57)
Global health status/QoL: Week 78	10.32 (16.44)
Global health status/QoL: Week 81	16.67 (23.57)
Global health status/QoL: Week 84	10.90 (14.98)
Global health status/QoL: Week 87	11.11 (19.25)
Global health status/QoL: Week 90	4.17 (11.79)
Global health status/QoL: Week 93	-29.17 (41.25)
Global health status/QoL: Week 96	0.00 (22.05)
Global health status/QoL: Week 99	-16.67
Global health status/QoL: Week 105	-16.67
Global health status/QoL: Week 111	0.00
Global health status/QoL: Week 117	0.00
Global health status/QoL: Last visit	7.99 (21.27)
Physical functioning: Baseline	69.96 (24.43)
Physical functioning: Week 6	4.69 (17.44)
Physical functioning: Week 9	0.00
Physical functioning: Week 12	4.20 (22.37)
Physical functioning: Week 15	0.00
Physical functioning: Week 18	7.58 (18.23)
Physical functioning: Week 21	0.00
Physical functioning: Week 24	4.13 (16.33)
Physical functioning: Week 27	3.33 (4.71)
Physical functioning: Week 30	2.22 (17.39)
Physical functioning: Week 33	0.00 (13.33)
Physical functioning: Week 36	4.21 (18.10)
Physical functioning: Week 39	3.33 (14.14)
Physical functioning: Week 42	6.85 (18.89)
Physical functioning: Week 45	-3.33 (22.11)
Physical functioning: Week 48	5.25 (16.81)
Physical functioning: Week 51	0.00 (18.86)
Physical functioning: Week 54	6.67 (18.32)
Physical functioning: Week 57	0.00 (20.55)
Physical functioning: Week 60	7.56 (22.67)
Physical functioning: Week 63	-6.67 (11.55)
Physical functioning: Week 66	8.97 (19.13)
Physical functioning: Week 69	8.33 (16.67)
Physical functioning: Week 72	4.20 (22.70)
Physical functioning: Week 75	0.00 (0.00)
Physical functioning: Week 78	6.98 (19.83)
Physical functioning: Week 81	0.00 (0.00)
Physical functioning: Week 84	3.08 (21.71)
Physical functioning: Week 87	-6.67 (11.55)
Physical functioning: Week 90	7.50 (18.32)
Physical functioning: Week 93	-26.67 (28.28)
Physical functioning: Week 96	33.33 (11.55)
Physical functioning: Week 99	-6.67
Physical functioning: Week 105	0.00
Physical functioning: Week 111	0.00
Physical functioning: Week 117	0.00
Physical functioning: Last visit	2.28 (21.64)
Role functioning: Baseline	58.86 (34.06)
Role functioning: Week 6	14.84 (32.00)
Role functioning: Week 9	0.00
Role functioning: Week 12	12.65 (32.69)
Role functioning: Week 15	0.00
Role functioning: Week 18	12.42 (31.94)
Role functioning: Week 21	0.00
Role functioning: Week 24	8.73 (27.85)
Role functioning: Week 27	-8.33 (11.79)
Role functioning: Week 30	9.83 (24.70)
Role functioning: Week 33	-33.33 (33.33)
Role functioning: Week 36	9.65 (24.70)
Role functioning: Week 39	-33.33 (0.00)
Role functioning: Week 42	6.48 (28.81)
Role functioning Week 45	-20.83 (15.96)
Role functioning: Week 48	10.94 (24.54)
Role functioning: Week 51	-16.67 (23.57)
Role functioning: Week 54	7.29 (24.30)
Role functioning: Week 57	-13.33 (18.26)
Role functioning: Week 60	8.89 (27.24)
Role functioning: Week 63	-5.56 (9.62)
Role functioning: Week 66	8.97 (29.90)
Role functioning: Week 69	-16.67 (33.33)
Role functioning: Week 72	7.97 (27.46)
Role functioning: Week 75	0.00 (0.00)
Role functioning: Week 78	9.52 (28.66)
Role functioning: Week 81	0.00 (0.00)
Role functioning: Week 84	5.13 (31.46)
Role functioning: Week 87	-11.11 (19.25)
Role functioning: Week 90	-4.17 (19.42)
Role functioning: Week 93	-41.67 (35.36)
Role functioning: Week 96	11.11 (19.25)
Role functioning: Week 99	-16.67
Role functioning: Week 105	0.00
Role functioning: Week 111	0.00
Role functioning: Week 117	0.00
Role functioning: Last visit	9.36 (34.47)
Emotional functioning: Baseline	73.49 (21.40)
Emotional functioning: Week 6	7.99 (18.75)
Emotional functioning: Week 9	0.00
Emotional functioning: Week 12	11.01 (17.04)
Emotional functioning: Week 15	0.00
Emotional functioning: Week 18	13.44 (21.17)
Emotional functioning: Week 21	0.00
Emotional functioning: Week 24	10.37 (16.75)
Emotional functioning: Week 27	-4.17 (5.89)
Emotional functioning: Week 30	9.40 (20.34)
Emotional functioning: Week 33	-30.56 (26.79)
Emotional functioning: Week 36	7.89 (19.85)
Emotional functioning: Week 39	-4.17 (5.89)
Emotional functioning: Week 42	7.41 (18.12)
Emotional functioning Week 45	-6.25 (7.98)
Emotional functioning: Week 48	6.73 (15.23)
Emotional functioning: Week 51	0.00 (0.00)
Emotional functioning: Week 54	3.49 (13.40)
Emotional functioning: Week 57	-6.67 (18.07)
Emotional functioning: Week 60	3.33 (14.12)
Emotional functioning: Week 63	-11.11 (34.69)
Emotional functioning: Week 66	5.45 (14.52)
Emotional functioning: Week 69	-8.33 (26.35)
Emotional functioning: Week 72	5.07 (21.43)
Emotional functioning: Week 75	8.33 (11.79)
Emotional functioning: Week 78	-1.19 (19.77)
Emotional functioning: Week 81	4.17 (5.89)
Emotional functioning: Week 84	1.28 (19.79)
Emotional functioning: Week 87	-11.11 (34.69)
Emotional functioning: Week 90	1.04 (8.26)
Emotional functioning: Week 93	-12.50 (17.68)
Emotional functioning: Week 96	11.11 (19.25)
Emotional functioning: Week 99	0.00
Emotional functioning: Week 105	0.00
Emotional functioning: Week 111	0.00
Emotional functioning: Week 117	0.00
Emotional functioning: Last visit	4.76 (19.86)
Cognitive functioning: Baseline	77.85 (24.13)
Cognitive functioning: Week 6	2.34 (20.76)
Cognitive functioning: Week 9	0.00
Cognitive functioning: Week 12	2.78 (15.44)
Cognitive functioning: Week 15	0.00
Cognitive functioning: Week 18	2.04 (15.82)
Cognitive functioning: Week 21	0.00
Cognitive functioning: Week 24	-3.25 (16.34)
Cognitive functioning: Week 27	0.00 (0.00)
Cognitive functioning: Week 30	-1.28 (17.68)
Cognitive functioning: Week 33	-27.78 (25.46)
Cognitive functioning: Week 36	-2.63 (13.16)
Cognitive functioning: Week 39	-25.00 (35.36)
Cognitive functioning: Week 42	-0.46 (14.08)
Cognitive functioning Week 45	-4.17 (51.59)
Cognitive functioning: Week 48	-6.06 (21.58)
Cognitive functioning: Week 51	-33.33 (0.00)
Cognitive functioning: Week 54	-7.53 (22.29)
Cognitive functioning: Week 57	0.00 (31.18)
Cognitive functioning: Week 60	-6.11 (21.66)
Cognitive functioning: Week 63	11.11 (19.25)
Cognitive functioning: Week 66	-8.97 (22.23)
Cognitive functioning: Week 69	4.17 (8.33)
Cognitive functioning: Week 72	-7.97 (20.64)
Cognitive functioning: Week 75	0.00 (0.00)
Cognitive functioning: Week 78	-9.52 (25.59)
Cognitive functioning: Week 81	0.00 (0.00)
Cognitive functioning: Week 84	-3.85 (20.59)
Cognitive functioning: Week 87	-11.11 (19.25)
Cognitive functioning: Week 90	-8.33 (15.43)
Cognitive functioning: Week 93	0.00 (0.00)
Cognitive functioning: Week 96	-22.22 (19.25)
Cognitive functioning: Week 99	0.00
Cognitive functioning: Week 105	0.00
Cognitive functioning: Week 111	0.00
Cognitive functioning: Week 117	0.00
Cognitive functioning: Last visit	-4.79 (24.45)
Social functioning: Baseline	60.55 (35.32)
Social functioning: Week 6	11.20 (23.20)
Social functioning: Week 9	0.00
Social functioning: Week 12	10.19 (27.93)
Social functioning: Week 15	0.00
Social functioning: Week 18	13.27 (25.45)
Social functioning: Week 21	0.00
Social functioning: Week 24	8.54 (26.38)
Social functioning: Week 27	16.67 (23.57)
Social functioning: Week 30	14.53 (31.11)
Social functioning: Week 33	5.56 (25.46)
Social functioning: Week 36	9.21 (32.35)
Social functioning: Week 39	-8.33 (11.79)
Social functioning: Week 42	8.80 (30.47)
Social functioning: Week 45	4.17 (20.97)
Social functioning: Week 48	16.16 (29.31)
Social functioning: Week 51	-8.33 (11.79)
Social functioning: Week 54	12.37 (28.53)
Social functioning: Week 57	3.33 (18.26)
Social functioning: Week 60	8.33 (25.43)
Social functioning: Week 63	0.00 (33.33)
Social functioning: Week 66	5.77 (31.95)
Social functioning: Week 69	20.83 (25.00)
Social functioning: Week 72	11.59 (23.80)
Social functioning: Week 75	16.67 (23.57)
Social functioning: Week 78	12.70 (23.51)
Social functioning: Week 81	16.67 (23.57)
Social functioning: Week 84	8.97 (29.36)
Social functioning: Week 87	27.78 (25.46)
Social functioning: Week 90	14.58 (16.52)
Social functioning: Week 93	-8.33 (82.50)
Social functioning: Week 96	16.67 (16.67)
Social functioning: Week 99	0.00
Social functioning: Week 105	0.00
Social functioning: Week 111	0.00
Social functioning: Week 117	0.00
Social functioning: Last visit	3.20 (30.39)
Fatigue: Baseline	45.57 (27.02)
Fatigue: Week 6	-10.94 (25.70)
Fatigue: Week 9	-11.11
Fatigue: Week 12	-11.11 (27.73)
Fatigue: Week 15	0.00
Fatigue: Week 18	-12.85 (24.88)
Fatigue: Week 21	0.00
Fatigue: Week 24	-10.05 (22.06)
Fatigue: Week 27	5.56 (7.86)
Fatigue: Week 30	-9.97 (23.47)
Fatigue: Week 33	14.81 (6.42)
Fatigue: Week 36	-10.23 (25.75)
Fatigue: Week 39	5.56 (7.86)
Fatigue: Week 42	-9.26 (21.50)
Fatigue: Week 45	0.00 (24.00)
Fatigue: Week 48	-11.11 (22.93)
Fatigue: Week 51	0.00 (47.14)
Fatigue: Week 54	-7.64 (18.39)
Fatigue: Week 57	4.44 (16.85)
Fatigue: Week 60	-7.78 (21.27)
Fatigue: Week 63	7.41 (23.13)
Fatigue: Week 66	-7.69 (20.07)
Fatigue: Week 69	-8.33 (10.64)
Fatigue: Week 72	-8.21 (22.28)
Fatigue: Week 75	-5.56 (7.86)
Fatigue: Week 78	-6.35 (23.19)
Fatigue: Week 81	-5.56 (7.86)
Fatigue: Week 84	-9.40 (18.62)
Fatigue: Week 87	0.00 (11.11)
Fatigue: Week 90	-8.33 (17.57)
Fatigue: Week 93	33.33 (31.43)
Fatigue: Week 96	-18.52 (6.42)
Fatigue: Week 99	0.00
Fatigue: Week 105	0.00
Fatigue: Week 111	0.00
Fatigue: Week 117	0.00
Fatigue: Last visit	-6.85 (21.65)
Nausea and vomiting: Baseline	15.61 (20.73)
Nausea and vomiting: Week 6	-6.77 (19.63)
Nausea and vomiting: Week 9	0.00
Nausea and vomiting: Week 12	-8.02 (21.66)
Nausea and vomiting: Week 15	0.00
Nausea and vomiting: Week 18	-9.15 (19.81)
Nausea and vomiting: Week 21	0.00
Nausea and vomiting: Week 24	-9.13 (18.48)
Nausea and vomiting: Week 27	-8.33 (11.79)
Nausea and vomiting: Week 30	-5.98 (17.31)
Nausea and vomiting: Week 33	11.11 (25.46)
Nausea and vomiting: Week 36	-7.46 (17.63)
Nausea and vomiting: Week 39	16.67 (23.57)
Nausea and vomiting: Week 42	-8.80 (18.47)
Nausea and vomiting: Week 45	4.17 (8.33)
Nausea and vomiting: Week 48	-9.38 (19.37)
Nausea and vomiting: Week 51	8.33 (11.79)
Nausea and vomiting: Week 54	-8.85 (19.85)
Nausea and vomiting: Week 57	6.67 (14.91)
Nausea and vomiting: Week 60	-6.67 (17.29)
Nausea and vomiting: Week 63	11.11 (19.25)
Nausea and vomiting: Week 66	-7.05 (20.10)
Nausea and vomiting: Week 69	0.00 (0.00)
Nausea and vomiting: Week 72	-5.80 (19.85)
Nausea and vomiting: Week 75	0.00 (0.00)
Nausea and vomiting: Week 78	-5.56 (13.26)
Nausea and vomiting: Week 81	0.00 (0.00)
Nausea and vomiting: Week 84	-6.41 (12.80)
Nausea and vomiting: Week 87	5.56 (9.62)
Nausea and vomiting: Week 90	2.08 (13.91)
Nausea and vomiting: Week 93	0.00 (0.00)
Nausea and vomiting: Week 96	0.00 (16.67)
Nausea and vomiting: Week 99	0.00
Nausea and vomiting: Week 105	0.00
Nausea and vomiting: Week 111	0.00
Nausea and vomiting: Week 117	0.00
Nausea and vomiting: Last visit	-6.85 (20.38)
Pain: Baseline	36.29 (33.63)
Pain: Week 6	-12.50 (33.47)
Pain: Week 9	0.00
Pain: Week 12	-14.81 (32.48)
Pain: Week 15	0.00
Pain: Week 18	-13.07 (33.55)
Pain: Week 21	0.00
Pain: Week 24	-6.35 (31.44)
Pain: Week 27	8.33 (11.79)
Pain: Week 30	-5.13 (33.37)
Pain: Week 33	5.56 (9.62)
Pain: Week 36	-6.14 (34.31)
Pain: Week 39	-8.33 (11.79)
Pain: Week 42	-5.09 (23.17)
Pain: Week 45	8.33 (21.52)
Pain: Week 48	-4.55 (17.81)
Pain: Week 51	-25.00 (11.79)
Pain: Week 54	-0.52 (24.86)
Pain: Week 57	0.00 (39.09)
Pain: Week 60	0.56 (14.17)
Pain: Week 63	-5.56 (9.62)
Pain: Week 66	-5.13 (23.46)
Pain: Week 69	-4.17 (15.96)
Pain: Week 72	-5.07 (28.62)
Pain: Week 75	-8.33 (11.79)
Pain: Week 78	1.59 (15.73)
Pain: Week 81	-8.33 (11.79)
Pain: Week 84	-5.13 (19.70)
Pain: Week 87	-5.56 (9.62)
Pain: Week 90	-8.33 (25.20)
Pain: Week 93	25.00 (35.36)
Pain: Week 96	-11.11 (53.58)
Pain: Week 99	0.00
Pain: Week 105	0.00
Pain: Week 111	0.00
Pain: Week 117	0.00
Pain: Last visit	-9.36 (29.92)
Dyspnoea: Baseline	33.33 (30.86)
Dyspnoea: Week 6	-12.17 (32.96)
Dyspnoea : Week 9	0.00
Dyspnoea: Week 12	-10.69 (32.54)
Dyspnoea: Week 15	0.00
Dyspnoea: Week 18	-12.67 (30.78)
Dyspnoea: Week 21	0.00
Dyspnoea: Week 24	-7.50 (25.58)
Dyspnoea: Week 27	0.00 (0.00)
Dyspnoea: Week 30	-7.89 (26.21)
Dyspnoea: Week 33	0.00 (33.33)
Dyspnoea: Week 36	-7.21 (27.37)
Dyspnoea: Week 39	-16.67 (23.57)
Dyspnoea: Week 42	-5.71 (27.40)
Dyspnoea: Week 45	0.00 (27.22)
Dyspnoea: Week 48	-6.25 (28.63)
Dyspnoea: Week 51	0.00 (0.00)
Dyspnoea: Week 54	-7.29 (23.55)
Dyspnoea: Week 57	-6.67 (14.91)
Dyspnoea: Week 60	-1.11 (22.29)
Dyspnoea: Week 63	-11.11 (19.25)
Dyspnoea: Week 66	-8.97 (24.14)
Dyspnoea: Week 69	-8.33 (16.67)
Dyspnoea: Week 72	-1.45 (32.53)
Dyspnoea: Week 75	-16.67 (23.57)
Dyspnoea: Week 78	-4.76 (21.82)
Dyspnoea: Week 81	-16.67 (23.57)
Dyspnoea: Week 84	0.00 (23.57)
Dyspnoea: Week 87	-11.11 (19.25)
Dyspnoea: Week 90	8.33 (29.55)
Dyspnoea: Week 93	16.67 (23.57)
Dyspnoea: Week 96	-11.11 (38.49)
Dyspnoea: Week 99	33.33
Dyspnoea: Week 105	0.00
Dyspnoea: Week 111	0.00
Dyspnoea: Week 117	0.00
Dyspnoea: Last visit	-4.63 (33.71)
Insomnia: Baseline	31.22 (30.82)
Insomnia: Week 6	-9.38 (29.38)
Insomnia: Week 9	0.00
Insomnia: Week 12	-9.26 (34.52)
Insomnia: Week 15	0.00
Insomnia: Week 18	-3.27 (37.86)
Insomnia: Week 21	0.00
Insomnia: Week 24	-3.17 (36.67)
Insomnia: Week 27	0.00 (0.00)
Insomnia: Week 30	-9.40 (33.29)
Insomnia: Week 33	44.44 (50.92)
Insomnia: Week 36	-8.77 (40.03)
Insomnia: Week 39	83.33 (23.57)
Insomnia: Week 42	-5.56 (25.82)
Insomnia: Week 45	41.67 (31.91)
Insomnia: Week 48	-3.13 (29.77)
Insomnia: Week 51	50.00 (23.57)
Insomnia: Week 54	-2.08 (28.00)
Insomnia: Week 57	40.00 (43.46)
Insomnia: Week 60	-1.11 (28.34)
Insomnia: Week 63	0.00 (33.33)
Insomnia: Week 66	-5.33 (32.89)
Insomnia: Week 69	0.00 (27.22)
Insomnia: Week 72	0.00 (26.59)
Insomnia: Week 75	0.00 (0.00)
Insomnia: Week 78	1.59 (22.30)
Insomnia: Week 81	0.00 (0.00)
Insomnia: Week 84	0.00 (36.00)
Insomnia: Week 87	11.11 (19.25)
Insomnia: Week 90	0.00 (30.86)
Insomnia: Week 93	0.00 (0.00)
Insomnia: Week 96	22.22 (38.49)
Insomnia: Week 99	0.00
Insomnia: Week 105	0.00
Insomnia: Week 111	0.00
Insomnia: Week 117	0.00
Insomnia: Last visit	-1.83 (35.09)
Appetite loss: Baseline	29.96 (33.16)
Appetite loss: Week 6	-16.67 (30.28)
Appetite loss: Week 9	0.00
Appetite loss: Week 12	-18.52 (36.44)
Appetite loss: Week 15	0.00
Appetite loss: Week 18	-20.26 (33.39)
Appetite loss: Week 21	0.00
Appetite loss: Week 24	-19.84 (29.50)
Appetite loss: Week 27	-16.67 (23.57)
Appetite loss: Week 30	-13.68 (23.84)
Appetite loss: Week 33	-44.44 (19.25)
Appetite loss: Week 36	-14.91 (27.62)
Appetite loss: Week 39	-50.00 (23.57)
Appetite loss: Week 42	-16.67 (32.37)
Appetite loss: Week 45	-8.33 (41.94)
Appetite loss: Week 48	-20.83 (34.65)
Appetite loss: Week 51	-33.33 (47.14)
Appetite loss: Week 54	-18.75 (32.72)
Appetite loss: Week 57	-20.00 (29.81)
Appetite loss: Week 60	-20.00 (31.07)
Appetite loss: Week 63	0.00 (0.00)
Appetite loss: Week 66	-23.08 (33.69)
Appetite loss: Week 69	-16.67 (33.33)
Appetite loss: Week 72	-23.19 (30.87)
Appetite loss: Week 75	0.00 (0.00)
Appetite loss: Week 78	-20.63 (30.69)
Appetite loss: Week 81	0.00 (0.00)
Appetite loss: Week 84	-25.64 (36.40)
Appetite loss: Week 87	11.11 (19.25)
Appetite loss: Week 90	-20.83 (39.59)
Appetite loss: Week 93	0.00 (0.00)
Appetite loss: Week 96	-55.56 (50.92)
Appetite loss: Week 99	0.00
Appetite loss: Week 105	0.00
Appetite loss: Week 111	0.00
Appetite loss: Week 117	0.00
Appetite loss: Last visit	-13.70 (33.72)
Constipation: Baseline	20.25 (26.38)
Constipation: Week 6	9.90 (30.68)
Constipation: Week 9	0.00
Constipation: Week 12	1.85 (31.33)
Constipation: Week 15	33.33
Constipation: Week 18	4.58 (25.84)
Constipation: Week 21	0.00
Constipation: Week 24	2.38 (29.81)
Constipation: Week 27	33.33 (47.14)
Constipation: Week 30	5.13 (27.08)
Constipation: Week 33	11.11 (50.92)
Constipation: Week 36	5.26 (21.26)
Constipation: Week 39	16.67 (23.57)
Constipation: Week 42	9.26 (24.70)
Constipation: Week 45	50.00 (19.25)
Constipation: Week 48	1.04 (26.07)
Constipation: Week 51	-16.67 (23.57)
Constipation: Week 54	6.45 (23.44)
Constipation: Week 57	26.67 (43.46)
Constipation: Week 60	6.67 (22.15)
Constipation: Week 63	44.44 (38.49)
Constipation: Week 66	12.82 (26.79)
Constipation: Week 69	-8.33 (16.67)
Constipation: Week 72	4.35 (25.23)
Constipation: Week 75	33.33 (47.14)
Constipation: Week 78	7.94 (17.97)
Constipation: Week 81	33.33 (47.14)
Constipation: Week 84	7.69 (19.97)
Constipation: Week 87	22.22 (38.49)
Constipation: Week 90	8.33 (15.43)
Constipation: Week 93	33.33 (47.14)
Constipation: Week 96	-11.11 (50.92)
Constipation: Week 99	33.33
Constipation: Week 105	0.00
Constipation: Week 111	0.00
Constipation: Week 117	0.00
Constipation: Last visit	8.68 (31.93)
Diarrhoea: Baseline	13.25 (23.01)
Diarrhoea: Week 6	-7.41 (25.00)
Diarrhoea: Week 9	0.00
Diarrhoea: Week 12	-6.29 (23.62)
Diarrhoea: Week 15	0.00
Diarrhoea: Week 18	-5.56 (25.11)
Diarrhoea: Week 21	0.00
Diarrhoea: Week 24	-4.17 (28.43)
Diarrhoea: Week 27	-16.67 (23.57)
Diarrhoea: Week 30	-8.55 (23.84)
Diarrhoea: Week 33	-16.67 (23.57)
Diarrhoea: Week 36	-7.89 (23.80)
Diarrhoea: Week 39	0.00
Diarrhoea: Week 42	-6.48 (26.21)
Diarrhoea: Week 45	0.00 (0.00)
Diarrhoea: Week 48	-3.03 (28.09)
Diarrhoea: Week 51	0.00
Diarrhoea: Week 54	-6.25 (26.01)
Diarrhoea: Week 57	0.00 (0.00)
Diarrhoea: Week 60	-1.11 (32.14)
Diarrhoea: Week 63	0.00 (0.00)
Diarrhoea: Week 66	-7.69 (30.27)
Diarrhoea: Week 69	11.11 (19.25)
Diarrhoea: Week 72	-7.25 (28.35)
Diarrhoea: Week 75	0.00 (0.00)
Diarrhoea: Week 78	-6.67 (25.59)
Diarrhoea: Week 81	0.00 (0.00)
Diarrhoea: Week 84	2.78 (26.43)
Diarrhoea: Week 87	11.11 (19.25)
Diarrhoea: Week 90	9.52 (16.27)
Diarrhoea: Week 93	0.00 (0.00)
Diarrhoea: Week 96	33.33 (47.14)
Diarrhoea: Week 99	0.00
Diarrhoea: Week 105	0.00
Diarrhoea: Week 111	0.00
Diarrhoea: Week 117	0.00
Diarrhoea: Last visit	-2.31 (28.15)
Financial difficulties: Baseline	30.80 (33.24)
Financial difficulties: Week 6	-2.60 (21.66)
Financial difficulties: Week 9	0.00
Financial difficulties: Week 12	-4.32 (23.39)
Financial difficulties: Week 15	0.00
Financial difficulties: Week 18	-4.76 (21.52)
Financial difficulties: Week 21	0.00
Financial difficulties: Week 24	-2.44 (26.24)
Financial difficulties: Week 27	0.00 (0.00)
Financial difficulties: Week 30	-6.84 (23.17)
Financial difficulties: Week 33	11.11 (19.25)
Financial difficulties: Week 36	-6.14 (27.79)
Financial difficulties: Week 39	16.67 (23.57)
Financial difficulties: Week 42	-6.48 (20.81)
Financial difficulties: Week 45	8.33 (16.67)
Financial difficulties: Week 48	-8.08 (23.61)
Financial difficulties: Week 51	16.67 (23.57)
Financial difficulties: Week 54	-2.15 (27.13)
Financial difficulties: Week 57	6.67 (14.91)
Financial difficulties: Week 60	-3.33 (22.06)
Financial difficulties: Week 63	0.00 (0.00)
Financial difficulties: Week 66	-2.56 (28.16)
Financial difficulties: Week 69	-8.33 (16.67)
Financial difficulties: Week 72	5.80 (25.92)
Financial difficulties: Week 75	0.00 (0.00)
Financial difficulties: Week 78	0.00 (34.96)
Financial difficulties: Week 81	0.00 (0.00)
Financial difficulties: Week 84	12.82 (34.80)
Financial difficulties: Week 87	0.00 (0.00)
Financial difficulties: Week 90	-4.17 (21.36)
Financial difficulties: Week 93	-16.67 (23.57)
Financial difficulties: Week 96	22.22 (38.49)
Financial difficulties: Week 99	0.00
Financial difficulties: Week 105	0.00
Financial difficulties: Week 111	0.00
Financial difficulties: Week 117	0.00
Financial difficulties: Last visit	1.83 (32.82)

28. Secondary Outcome

Title	Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II
Description	EORTC QLQ-LC13 consisted of 13 questions for dyspnea (3 items) and 10 single items (cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm/shoulder, other pain). Questions used 4-point scale (1 'Not at all' to 4 'Very much'). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning, lower score indicates lower level of functioning. 'Baseline' category for any parameter below represents absolute data at baseline.
Time Frame	Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)

Outcome Measure Data

Analysis Population Description

Phase II safety population. 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specified timepoint.

Arm/Group Title	Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
Measure Participants	79
Dyspnoea: Baseline	30.85 (27.13)
Dyspnoea: Week 6	-8.24 (22.57)
Dyspnoea: Week 9	0.00
Dyspnoea: Week 12	-7.64 (20.65)
Dyspnoea: Week 15	0.00
Dyspnoea: Week 18	-11.35 (21.67)
Dyspnoea: Week 21	0.00
Dyspnoea: Week 24	-7.41 (21.68)
Dyspnoea: Week 27	5.56 (7.86)
Dyspnoea: Week 30	-4.09 (20.41)
Dyspnoea: Week 33	-11.11 (11.11)
Dyspnoea: Week 36	-5.41 (21.69)
Dyspnoea: Week 39	-5.56 (7.86)
Dyspnoea: Week 42	-8.64 (20.25)
Dyspnoea: Week 45	-2.78 (27.78)
Dyspnoea: Week 48	-7.74 (24.77)
Dyspnoea: Week 51	-27.78 (23.57)
Dyspnoea: Week 54	-5.02 (19.63)
Dyspnoea: Week 57	-2.22 (16.48)
Dyspnoea: Week 60	-7.28 (19.54)
Dyspnoea: Week 63	3.70 (16.97)
Dyspnoea: Week 66	-6.22 (25.27)
Dyspnoea: Week 69	-13.89 (29.22)
Dyspnoea: Week 72	-6.76 (26.96)
Dyspnoea: Week 75	-5.56 (7.86)
Dyspnoea: Week 78	-8.19 (22.48)
Dyspnoea: Week 81	-5.56 (7.86)
Dyspnoea: Week 84	-9.40 (16.26)
Dyspnoea: Week 87	7.41 (23.13)
Dyspnoea: Week 90	-5.56 (17.82)
Dyspnoea: Week 93	22.22 (0.00)
Dyspnoea: Week 96	-51.85 (23.13)
Dyspnoea: Week 99	11.11
Dyspnoea: Week 105	0.00
Dyspnoea: Week 111	0.00
Dyspnoea: Week 117	0.00
Dyspnoea: Last visit	-6.44 (23.45)
Coughing: Baseline	33.76 (27.47)
Coughing: Week 6	-13.89 (31.47)
Coughing: Week 9	0.00
Coughing: Week 12	-12.82 (27.34)
Coughing: Week 15	0.00
Coughing: Week 18	-13.61 (24.46)
Coughing: Week 21	0.00
Coughing: Week 24	-9.17 (31.11)
Coughing: Week 27	0.00 (0.00)
Coughing: Week 30	-1.75 (24.44)
Coughing: Week 33	-22.22 (19.25)
Coughing: Week 36	-8.77 (28.67)
Coughing: Week 39	-50.00 (23.57)
Coughing: Week 42	-0.93 (27.01)
Coughing: Week 45	-8.33 (50.00)
Coughing: Week 48	-4.04 (35.12)
Coughing: Week 51	-33.33 (0.00)
Coughing: Week 54	-8.33 (25.40)
Coughing: Week 57	-20.00 (29.81)
Coughing: Week 60	-2.30 (29.45)
Coughing: Week 63	0.00 (33.33)
Coughing: Week 66	-5.13 (27.80)
Coughing: Week 69	-25.00 (31.91)
Coughing: Week 72	-7.25 (28.35)
Coughing: Week 75	-16.67 (23.57)
Coughing: Week 78	-6.67 (35.21)
Coughing: Week 81	-16.67 (23.57)
Coughing: Week 84	-15.38 (29.24)
Coughing: Week 87	0.00 (33.33)
Coughing: Week 90	-8.33 (29.55)
Coughing: Week 93	16.67 (23.57)
Coughing: Week 96	-44.44 (19.25)
Coughing: Week 99	0.00
Coughing: Week 105	0.00
Coughing: Week 111	0.00
Coughing: Week 117	0.00
Coughing: Last visit	-5.48 (32.87)
Hemoptysis: Baseline	1.27 (6.41)
Hemoptysis: Week 6	-1.11 (6.03)
Hemoptysis: Week 9	0.00
Hemoptysis: Week 12	-1.28 (6.47)
Hemoptysis: Week 15	0.00
Hemoptysis: Week 18	-1.36 (6.66)
Hemoptysis: Week 21	0.00
Hemoptysis: Week 24	-1.67 (7.36)
Hemoptysis: Week 27	0.00 (0.00)
Hemoptysis: Week 30	0.00 (13.25)
Hemoptysis: Week 33	0.00 (0.00)
Hemoptysis: Week 36	-1.75 (7.54)
Hemoptysis: Week 39	0.00 (0.00)
Hemoptysis: Week 42	0.00 (7.97)
Hemoptysis: Week 45	0.00 (0.00)
Hemoptysis: Week 48	-1.01 (5.80)
Hemoptysis: Week 51	0.00 (0.00)
Hemoptysis: Week 54	1.08 (10.48)
Hemoptysis: Week 57	0.00 (0.00)
Hemoptysis: Week 60	-1.15 (6.19)
Hemoptysis: Week 63	0.00 (0.00)
Hemoptysis: Week 66	-1.28 (6.54)
Hemoptysis: Week 69	0.00 (0.00)
Hemoptysis: Week 72	2.90 (22.28)
Hemoptysis: Week 75	0.00 (0.00)
Hemoptysis: Week 78	-1.67 (7.45)
Hemoptysis: Week 81	0.00 (0.00)
Hemoptysis: Week 84	-2.56 (9.25)
Hemoptysis: Week 87	0.00 (0.00)
Hemoptysis: Week 90	0.00 (0.00)
Hemoptysis: Week 93	0.00 (0.00)
Hemoptysis: Week 96	0.00 (0.00)
Hemoptysis: Week 99	0.00
Hemoptysis: Week 105	0.00
Hemoptysis: Week 111	0.00
Hemoptysis: Week 117	0.00
Hemoptysis: Last visit	-0.91 (7.80)
Sore mouth: Baseline	5.06 (16.09)
Sore mouth: Week 6	-1.11 (13.68)
Sore mouth: Week 9	0.00
Sore mouth: Week 12	0.64 (13.99)
Sore mouth: Week 15	0.00
Sore mouth: Week 18	-2.04 (17.22)
Sore mouth: Week 21	0.00
Sore mouth: Week 24	-0.85 (17.91)
Sore mouth: Week 27	0.00 (0.00)
Sore mouth: Week 30	2.56 (11.81)
Sore mouth: Week 33	22.22 (38.49)
Sore mouth: Week 36	1.75 (15.40)
Sore mouth: Week 39	16.67 (23.57)
Sore mouth: Week 42	-0.93 (9.71)
Sore mouth: Week 45	0.00 (0.00)
Sore mouth: Week 48	7.07 (26.03)
Sore mouth: Week 51	0.00 (0.00)
Sore mouth: Week 54	1.08 (13.56)
Sore mouth: Week 57	0.00 (23.57)
Sore mouth: Week 60	-1.15 (14.04)
Sore mouth: Week 63	0.00 (0.00)
Sore mouth: Week 66	-2.56 (13.07)
Sore mouth: Week 69	0.00 (0.00)
Sore mouth: Week 72	4.55 (18.67)
Sore mouth: Week 75	0.00 (0.00)
Sore mouth: Week 78	1.67 (7.45)
Sore mouth: Week 81	0.00 (0.00)
Sore mouth: Week 84	0.00 (0.00)
Sore mouth: Week 87	0.00 (0.00)
Sore mouth: Week 90	4.17 (11.79)
Sore mouth: Week 93	0.00 (0.00)
Sore mouth: Week 96	11.11 (19.25)
Sore mouth: Week 99	0.00
Sore mouth: Week 105	0.00
Sore mouth: Week 111	0.00
Sore mouth: Week 117	0.00
Sore mouth: Last visit	-0.46 (15.21)
Dysphagia: Baseline	4.64 (11.61)
Dysphagia: Week 6	-1.67 (11.36)
Dysphagia: Week 9	0.00
Dysphagia: Week 12	-0.64 (10.42)
Dysphagia: Week 15	0.00
Dysphagia: Week 18	-1.36 (11.70)
Dysphagia: Week 21	0.00
Dysphagia: Week 24	0.83 (11.91)
Dysphagia: Week 27	16.67 (23.57)
Dysphagia: Week 30	3.42 (14.90)
Dysphagia: Week 33	0.00 (33.33)
Dysphagia: Week 36	-0.88 (5.41)
Dysphagia: Week 39	-16.67 (23.57)
Dysphagia: Week 42	-0.93 (12.56)
Dysphagia: Week 45	0.00 (27.22)
Dysphagia: Week 48	2.02 (16.54)
Dysphagia: Week 51	-16.67 (23.57)
Dysphagia: Week 54	-1.08 (13.56)
Dysphagia: Week 57	6.67 (27.89)
Dysphagia: Week 60	-3.57 (13.88)
Dysphagia: Week 63	11.11 (19.25)
Dysphagia: Week 66	-1.28 (14.85)
Dysphagia: Week 69	0.00 (0.00)
Dysphagia: Week 72	1.45 (15.82)
Dysphagia: Week 75	0.00 (0.00)
Dysphagia: Week 78	0.00 (10.81)
Dysphagia: Week 81	0.00 (0.00)
Dysphagia: Week 84	2.56 (9.25)
Dysphagia: Week 87	0.00 (0.00)
Dysphagia: Week 90	0.00 (0.00)
Dysphagia: Week 93	0.00 (0.00)
Dysphagia: Week 96	0.00 (0.00)
Dysphagia: Week 99	0.00
Dysphagia: Week 105	0.00
Dysphagia: Week 111	0.00
Dysphagia: Week 117	0.00
Dysphagia: Last visit	2.74 (17.35)
Peripheral neuropathy: Baseline	13.08 (22.28)
Peripheral neuropathy: Week 6	6.11 (17.88)
Peripheral neuropathy: Week 9	0.00
Peripheral neuropathy: Week 12	1.28 (20.83)
Peripheral neuropathy: Week 15	0.00
Peripheral neuropathy: Week 18	2.72 (22.40)
Peripheral neuropathy: Week 21	0.00
Peripheral neuropathy: Week 24	4.17 (20.24)
Peripheral neuropathy: Week 27	-16.67 (23.57)
Peripheral neuropathy: Week 30	4.27 (24.40)
Peripheral neuropathy: Week 33	11.11 (19.25)
Peripheral neuropathy: Week 36	0.00 (18.98)
Peripheral neuropathy: Week 39	0.00 (0.00)
Peripheral neuropathy: Week 42	1.85 (21.00)
Peripheral neuropathy: Week 45	8.33 (16.67)
Peripheral neuropathy: Week 48	2.02 (23.48)
Peripheral neuropathy: Week 51	0.00 (0.00)
Peripheral neuropathy: Week 54	6.45 (26.41)
Peripheral neuropathy: Week 57	6.67 (27.89)
Peripheral neuropathy: Week 60	2.30 (23.45)
Peripheral neuropathy: Week 63	0.00 (0.00)
Peripheral neuropathy: Week 66	1.28 (24.00)
Peripheral neuropathy: Week 69	0.00 (0.00)
Peripheral neuropathy: Week 72	2.90 (28.27)
Peripheral neuropathy: Week 75	0.00 (0.00)
Peripheral neuropathy: Week 78	-3.33 (21.36)
Peripheral neuropathy: Week 81	0.00 (0.00)
Peripheral neuropathy: Week 84	12.82 (37.36)
Peripheral neuropathy: Week 87	0.00 (0.00)
Peripheral neuropathy: Week 90	16.67 (17.82)
Peripheral neuropathy: Week 93	0.00 (0.00)
Peripheral neuropathy: Week 96	55.56 (38.49)
Peripheral neuropathy: Week 99	0.00
Peripheral neuropathy: Week 105	0.00
Peripheral neuropathy: Week 111	0.00
Peripheral neuropathy: Week 117	0.00
Peripheral neuropathy: Last visit	1.37 (22.52)
Alopecia: Baseline	11.69 (25.80)
Alopecia: Week 6	-1.13 (22.29)
Alopecia: Week 9	0.00
Alopecia: Week 12	1.31 (31.24)
Alopecia: Week 15	0.00
Alopecia: Week 18	-4.96 (25.04)
Alopecia: Week 21	0.00
Alopecia: Week 24	-2.56 (27.98)
Alopecia: Week 27	0.00 (0.00)
Alopecia: Week 30	-3.51 (27.72)
Alopecia: Week 33	0.00 (0.00)
Alopecia: Week 36	0.90 (32.85)
Alopecia: Week 39	0.00 (0.00)
Alopecia: Week 42	-2.78 (20.12)
Alopecia: Week 45	0.00 (0.00)
Alopecia: Week 48	-5.21 (22.58)
Alopecia: Week 51	0.00 (0.00)
Alopecia: Week 54	-6.45 (15.91)
Alopecia: Week 57	-6.67 (14.91)
Alopecia: Week 60	-4.60 (19.36)
Alopecia: Week 63	-11.11 (19.25)
Alopecia: Week 66	-2.67 (27.08)
Alopecia: Week 69	-8.33 (16.67)
Alopecia: Week 72	-3.03 (33.98)
Alopecia: Week 75	0.00 (0.00)
Alopecia: Week 78	-8.33 (26.21)
Alopecia: Week 81	-16.67 (23.57)
Alopecia: Week 84	-2.56 (25.32)
Alopecia: Week 87	-11.11 (19.25)
Alopecia: Week 90	4.17 (21.36)
Alopecia: Week 93	0.00 (0.00)
Alopecia: Week 96	0.00 (0.00)
Alopecia: Week 99	0.00
Alopecia: Week 105	0.00
Alopecia: Week 111	0.00
Alopecia: Week 117	0.00
Alopecia: Last visit	-5.16 (27.97)
Pain in chest: Baseline	21.52 (28.26)
Pain in chest: Week 6	-16.67 (29.75)
Pain in chest: Week 9	0.00
Pain in chest: Week 12	-11.54 (23.69)
Pain in chest: Week 15	0.00
Pain in chest: Week 18	-8.84 (27.87)
Pain in chest: Week 21	0.00
Pain in chest: Week 24	-8.33 (23.57)
Pain in chest: Week 27	0.00 (0.00)
Pain in chest: Week 30	-3.42 (22.68)
Pain in chest: Week 33	-11.11 (19.25)
Pain in chest: Week 36	-6.14 (26.68)
Pain in chest: Week 39	-16.67 (23.57)
Pain in chest: Week 42	-6.48 (19.22)
Pain in chest: Week 45	-8.33 (41.94)
Pain in chest: Week 48	-6.06 (19.46)
Pain in chest: Week 51	-33.33 (0.00)
Pain in chest: Week 54	-4.30 (20.62)
Pain in chest: Week 57	-13.33 (38.01)
Pain in chest: Week 60	-3.45 (16.29)
Pain in chest: Week 63	-16.67 (23.57)
Pain in chest: Week 66	-2.56 (18.67)
Pain in chest: Week 69	-25.00 (31.91)
Pain in chest: Week 72	-2.90 (28.27)
Pain in chest: Week 75	-16.67 (23.57)
Pain in chest: Week 78	0.00 (18.73)
Pain in chest: Week 81	-16.67 (23.57)
Pain in chest: Week 84	-5.13 (22.96)
Pain in chest: Week 87	-11.11 (19.25)
Pain in chest: Week 90	-12.50 (24.80)
Pain in chest: Week 93	16.67 (23.57)
Pain in chest: Week 96	-22.22 (19.25)
Pain in chest: Week 99	0.00
Pain in chest: Week 105	0.00
Pain in chest: Week 111	0.00
Pain in chest: Week 117	0.00
Pain in chest: Last visit	-8.80 (26.83)
Pain in arm or shoulder: Baseline	16.88 (28.18)
Pain in arm or shoulder: Week 6	-7.22 (25.37)
Pain in arm or shoulder: Week 9	0.00
Pain in arm or shoulder: Week 12	-5.77 (30.05)
Pain in arm or shoulder: Week 15	0.00
Pain in arm or shoulder: Week 18	-4.86 (24.78)
Pain in arm or shoulder: Week 21	0.00
Pain in arm or shoulder: Week 24	-10.83 (27.62)
Pain in arm or shoulder: Week 27	-16.67 (23.57)
Pain in arm or shoulder: Week 30	-3.42 (23.93)
Pain in arm or shoulder: Week 33	-11.11 (38.49)
Pain in arm or shoulder: Week 36	-5.26 (33.36)
Pain in arm or shoulder: Week 39	-16.67 (23.57)
Pain in arm or shoulder: Week 42	-5.56 (25.82)
Pain in arm or shoulder: Week 45	0.00 (0.00)
Pain in arm or shoulder: Week 48	-6.06 (21.17)
Pain in arm or shoulder: Week 51	-16.67 (23.57)
Pain in arm or shoulder: Week 54	-1.08 (25.07)
Pain in arm or shoulder: Week 57	0.00 (23.57)
Pain in arm or shoulder: Week 60	-2.30 (26.62)
Pain in arm or shoulder: Week 63	0.00 (0.00)
Pain in arm or shoulder: Week 66	-3.85 (27.21)
Pain in arm or shoulder: Week 69	-16.67 (33.33)
Pain in arm or shoulder: Week 72	-4.35 (28.96)
Pain in arm or shoulder: Week 75	0.00 (0.00)
Pain in arm or shoulder: Week 78	-8.77 (24.45)
Pain in arm or shoulder: Week 81	0.00 (0.00)
Pain in arm or shoulder: Week 84	7.69 (38.86)
Pain in arm or shoulder: Week 87	0.00 (0.00)
Pain in arm or shoulder: Week 90	4.17 (21.36)
Pain in arm or shoulder: Week 93	0.00 (0.00)
Pain in arm or shoulder: Week 96	0.00 (33.33)
Pain in arm or shoulder: Week 99	0.00
Pain in arm or shoulder: Week 105	0.00
Pain in arm or shoulder: Week 111	0.00
Pain in arm or shoulder: Week 117	0.00
Pain in arm or shoulder: Last visit	0.00 (29.92)
Pain in other parts: Baseline	44.00 (36.42)
Pain in other parts: Week 6	-16.96 (42.78)
Pain in other parts: Week 9	0.00
Pain in other parts: Week 12	-11.59 (41.70)
Pain in other parts: Week 15	0.00
Pain in other parts: Week 18	-19.26 (41.74)
Pain in other parts: Week 21	0.00
Pain in other parts: Week 24	-19.30 (36.87)
Pain in other parts: Week 27	0.00 (0.00)
Pain in other parts: Week 30	-18.52 (37.75)
Pain in other parts: Week 33	0.00 (33.33)
Pain in other parts: Week 36	-18.52 (36.90)
Pain in other parts: Week 39	0.00 (94.28)
Pain in other parts: Week 42	-16.16 (37.38)
Pain in other parts: Week 45	-8.33 (56.93)
Pain in other parts: Week 48	-12.22 (34.45)
Pain in other parts: Week 51	0.00 (47.14)
Pain in other parts: Week 54	-14.94 (38.41)
Pain in other parts: Week 57	-13.33 (38.01)
Pain in other parts: Week 60	-15.38 (34.29)
Pain in other parts: Week 63	-44.44 (38.49)
Pain in other parts: Week 66	-10.61 (39.02)
Pain in other parts: Week 69	-8.33 (41.94)
Pain in other parts: Week 72	-15.00 (33.29)
Pain in other parts: Week 75	-16.67 (23.57)
Pain in other parts: Week 78	-5.26 (27.81)
Pain in other parts: Week 81	-16.67 (23.57)
Pain in other parts: Week 84	-12.12 (22.47)
Pain in other parts: Week 87	-22.22 (38.49)
Pain in other parts: Week 90	0.00 (36.51)
Pain in other parts: Week 93	33.33 (47.14)
Pain in other parts: Week 96	-33.33
Pain in other parts: Week 99	0.00
Pain in other parts: Week 105	0.00
Pain in other parts: Week 111	0.00
Pain in other parts: Week 117	0.00
Pain in other parts: Last visit	-12.56 (37.96)

Adverse Events

Time Frame	Baseline to up to 28 days after the last dose of alectinib (up to 284 weeks)
Adverse Event Reporting Description	Safety population
Arm/Group Title	Alectinib 300 mg (Fasted): Phase I		Alectinib 460 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase I		Alectinib 760 mg (Fed): Phase I		Alectinib 900 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase II
Arm/Group Description	Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 240 or 300 mg on Cycle 1 Day -3 and then received 300 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.		Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 460 mg on Cycle 1 Day -3 and then received 460 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.		Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 600 mg on Cycle 1 Day -3 and then received 600 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.		Participants received single dose of 20 or 40 mg alectinib capsules orally to make a dose of 760 mg on Cycle 1 Day -3 and then received 760 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.		Participants received single dose of 20 or 40 or 150 mg alectinib capsules orally to make a dose of 900 mg on Cycle 1 Day -3 and then received 900 mg BID dose for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.		Participants received 600 mg alectinib capsules orally BID from Cycle 1 Day 1 for 3-weekly cycles until disease progression, death or withdrawal for any other reasons.
All Cause Mortality
	Alectinib 300 mg (Fasted): Phase I		Alectinib 460 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase I		Alectinib 760 mg (Fed): Phase I		Alectinib 900 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase II
	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	7/7 (100%)		4/7 (57.1%)		6/13 (46.2%)		2/7 (28.6%)		9/13 (69.2%)		45/87 (51.7%)
Serious Adverse Events
	Alectinib 300 mg (Fasted): Phase I		Alectinib 460 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase I		Alectinib 760 mg (Fed): Phase I		Alectinib 900 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase II
	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	1/7 (14.3%)		2/7 (28.6%)		6/13 (46.2%)		0/7 (0%)		1/13 (7.7%)		21/87 (24.1%)
Blood and lymphatic system disorders
Anaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Cardiac disorders
Pericardial effusion	0/7 (0%)		0/7 (0%)		2/13 (15.4%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Ear and labyrinth disorders
Vertigo	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gastrointestinal disorders
Nausea	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Vomiting	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Intestinal obstruction	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
General disorders
Fatigue	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Non-cardiac chest pain	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Death	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Hepatobiliary disorders
Drug-induced liver injury	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Bile duct obstruction	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Infections and infestations
Bronchitis	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Pneumonia bacterial	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Influenza	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Lung infection	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Staphylococcal sepsis	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Pneumonia	0/7 (0%)		0/7 (0%)		2/13 (15.4%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Gastroenteritis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Injury, poisoning and procedural complications
Procedural pain	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Overdose	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Radiation necrosis	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Stroke-like migraine attacks after radiation therapy	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Metabolism and nutrition disorders
Hyperammonaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Hyponatraemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Tumour necrosis	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Nervous system disorders
Brain oedema	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Cerebral ventricle dilatation	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Embolic stroke	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Haemorrhage intracranial	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Hemiparesis	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Seizure	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Cerebrovascular accident	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Headache	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Renal and urinary disorders
Renal failure	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Chronic obstructive pulmonary disease	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Hypercapnia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Pneumothorax	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Vascular disorders
Haemorrhage	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		1/87 (1.1%)
Embolism	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Alectinib 300 mg (Fasted): Phase I		Alectinib 460 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase I		Alectinib 760 mg (Fed): Phase I		Alectinib 900 mg (Fed): Phase I		Alectinib 600 mg (Fed): Phase II
	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	7/7 (100%)		7/7 (100%)		12/13 (92.3%)		7/7 (100%)		13/13 (100%)		85/87 (97.7%)
Blood and lymphatic system disorders
Anaemia	1/7 (14.3%)		3/7 (42.9%)		0/13 (0%)		1/7 (14.3%)		4/13 (30.8%)		17/87 (19.5%)
Leukopenia	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		6/87 (6.9%)
Neutropenia	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Thrombocytopenia	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Cardiac disorders
Sinus bradycardia	0/7 (0%)		0/7 (0%)		4/13 (30.8%)		2/7 (28.6%)		0/13 (0%)		6/87 (6.9%)
Atrial fibrillation	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Atrioventricular block	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Bradycardia	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		8/87 (9.2%)
Bundle branch block left	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Cardiomyopathy	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Coronary artery disease	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Diastolic dysfunction	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Ventricular extrasystoles	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Ear and labyrinth disorders
Tinnitus	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Vertigo	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hypoacusis	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Endocrine disorders
Hypothyroidism	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Eye disorders
Visual impairment	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Eye irritation	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Eyelid oedema	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Periorbital oedema	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Vision blurred	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		7/87 (8%)
Vitreous floaters	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gastrointestinal disorders
Constipation	0/7 (0%)		2/7 (28.6%)		3/13 (23.1%)		3/7 (42.9%)		3/13 (23.1%)		34/87 (39.1%)
Nausea	2/7 (28.6%)		2/7 (28.6%)		3/13 (23.1%)		0/7 (0%)		3/13 (23.1%)		22/87 (25.3%)
Diarrhoea	0/7 (0%)		2/7 (28.6%)		2/13 (15.4%)		1/7 (14.3%)		3/13 (23.1%)		21/87 (24.1%)
Vomiting	1/7 (14.3%)		1/7 (14.3%)		2/13 (15.4%)		0/7 (0%)		0/13 (0%)		14/87 (16.1%)
Abdominal discomfort	1/7 (14.3%)		0/7 (0%)		2/13 (15.4%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Abdominal pain	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		2/13 (15.4%)		0/87 (0%)
Abdominal distension	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Abdominal pain upper	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Dry mouth	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		5/87 (5.7%)
Flatulence	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Abdominal pain lower	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Dental caries	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Haemorrhoids	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Oral disorder	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Stomatitis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Faecaloma	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gastrooesophageal reflux disease	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gingival swelling	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Noninfective gingivitis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Oesophagitis	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
General disorders
Fatigue	4/7 (57.1%)		3/7 (42.9%)		3/13 (23.1%)		5/7 (71.4%)		7/13 (53.8%)		36/87 (41.4%)
Oedema peripheral	1/7 (14.3%)		1/7 (14.3%)		2/13 (15.4%)		2/7 (28.6%)		3/13 (23.1%)		22/87 (25.3%)
Pain	0/7 (0%)		0/7 (0%)		3/13 (23.1%)		0/7 (0%)		1/13 (7.7%)		9/87 (10.3%)
Pyrexia	0/7 (0%)		1/7 (14.3%)		2/13 (15.4%)		0/7 (0%)		0/13 (0%)		5/87 (5.7%)
Asthenia	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Chest discomfort	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Chest pain	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		1/13 (7.7%)		5/87 (5.7%)
Face oedema	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gait disturbance	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Injection site haemorrhage	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Injection site reaction	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Mucosal inflammation	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Non-cardiac chest pain	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Axillary pain	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Influenza like illness	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Oedema	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Peripheral swelling	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/7 (0%)		2/7 (28.6%)		2/13 (15.4%)		0/7 (0%)		2/13 (15.4%)		7/87 (8%)
Infections and infestations
Upper respiratory tract infection	1/7 (14.3%)		2/7 (28.6%)		3/13 (23.1%)		0/7 (0%)		1/13 (7.7%)		14/87 (16.1%)
Urinary tract infection	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		2/13 (15.4%)		9/87 (10.3%)
Pneumonia	0/7 (0%)		0/7 (0%)		3/13 (23.1%)		0/7 (0%)		1/13 (7.7%)		6/87 (6.9%)
Oral herpes	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/87 (0%)
Tooth infection	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Viral upper respiratory tract infection	0/7 (0%)		2/7 (28.6%)		2/13 (15.4%)		3/7 (42.9%)		0/13 (0%)		5/87 (5.7%)
Conjunctivitis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Fungal skin infection	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gastroenteritis viral	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Rash pustular	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Rhinitis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Sinusitis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Viral infection	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Babesiosis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Infective exacerbation of chronic obstructive airways disease	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Influenza	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Onychomycosis	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Injury, poisoning and procedural complications
Excoriation	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Fall	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		5/87 (5.7%)
Post lumbar puncture syndrome	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Radiation injury	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Thermal burn	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Upper limb fracture	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Animal bite	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Fractured sacrum	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Investigations
Blood creatine phosphokinase increased	0/7 (0%)		4/7 (57.1%)		1/13 (7.7%)		4/7 (57.1%)		1/13 (7.7%)		20/87 (23%)
Alanine aminotransferase increased	1/7 (14.3%)		3/7 (42.9%)		3/13 (23.1%)		2/7 (28.6%)		1/13 (7.7%)		16/87 (18.4%)
Aspartate aminotransferase increased	1/7 (14.3%)		3/7 (42.9%)		2/13 (15.4%)		2/7 (28.6%)		1/13 (7.7%)		18/87 (20.7%)
Blood bilirubin increased	0/7 (0%)		1/7 (14.3%)		3/13 (23.1%)		1/7 (14.3%)		2/13 (15.4%)		10/87 (11.5%)
Blood creatinine increased	0/7 (0%)		1/7 (14.3%)		4/13 (30.8%)		1/7 (14.3%)		0/13 (0%)		5/87 (5.7%)
Blood alkaline phosphatase increased	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		1/7 (14.3%)		1/13 (7.7%)		12/87 (13.8%)
Electrocardiogram PR Prolongation	0/7 (0%)		0/7 (0%)		2/13 (15.4%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Neutrophil count decreased	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/87 (0%)
White blood cell count decreased	1/7 (14.3%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Blood lactate dehydrogenase increased	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Blood triglycerides increased	0/7 (0%)		2/7 (28.6%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Gamma-glutamyltransferase increased	1/7 (14.3%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Haemoglobin decreased	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Activated partial thromboplastin time prolonged	0/7 (0%)		0/7 (0%)		2/13 (15.4%)		0/7 (0%)		0/13 (0%)		8/87 (9.2%)
Blood cholesterol increased	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Blood phosphorus increased	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Ejection fraction decreased	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Heart rate irregular	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
International normalised ratio increased	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Neutrophil count	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Platelet count decreased	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Weight decreased	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		6/87 (6.9%)
Weight increased	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		17/87 (19.5%)
Blood testosterone decreased	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Electrocardiogram abnormal	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Prothrombin time prolonged	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/7 (0%)		2/7 (28.6%)		1/13 (7.7%)		3/7 (42.9%)		0/13 (0%)		6/87 (6.9%)
Hypertriglyceridaemia	0/7 (0%)		0/7 (0%)		2/13 (15.4%)		3/7 (42.9%)		1/13 (7.7%)		13/87 (14.9%)
Hypophosphataemia	0/7 (0%)		2/7 (28.6%)		1/13 (7.7%)		1/7 (14.3%)		1/13 (7.7%)		6/87 (6.9%)
Hypokalaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		3/13 (23.1%)		10/87 (11.5%)
Decreased appetite	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		9/87 (10.3%)
Fluid retention	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/87 (0%)
Dyslipidaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Hyperkalaemia	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hypoalbuminaemia	0/7 (0%)		2/7 (28.6%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		6/87 (6.9%)
Hypocalcaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Hypomagnesaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Hyponatraemia	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hypercalcaemia	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hypercholesterolaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Hyperphosphataemia	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hypoglycaemia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/7 (14.3%)		4/7 (57.1%)		2/13 (15.4%)		3/7 (42.9%)		2/13 (15.4%)		23/87 (26.4%)
Arthralgia	2/7 (28.6%)		1/7 (14.3%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		12/87 (13.8%)
Back pain	1/7 (14.3%)		1/7 (14.3%)		5/13 (38.5%)		2/7 (28.6%)		1/13 (7.7%)		12/87 (13.8%)
Musculoskeletal chest pain	3/7 (42.9%)		2/7 (28.6%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Pain in extremity	1/7 (14.3%)		2/7 (28.6%)		1/13 (7.7%)		1/7 (14.3%)		1/13 (7.7%)		0/87 (0%)
Musculoskeletal pain	1/7 (14.3%)		2/7 (28.6%)		2/13 (15.4%)		3/7 (42.9%)		0/13 (0%)		7/87 (8%)
Muscle spasms	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		1/7 (14.3%)		1/13 (7.7%)		0/87 (0%)
Muscular weakness	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		2/7 (28.6%)		0/13 (0%)		5/87 (5.7%)
Groin pain	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Joint swelling	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Muscle fatigue	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Musculoskeletal stiffness	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Myopathy	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Arthritis	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Flank pain	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Joint effusion	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Neck pain	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Nervous system disorders
Headache	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		4/13 (30.8%)		25/87 (28.7%)
Dysgeusia	1/7 (14.3%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		1/13 (7.7%)		8/87 (9.2%)
Dizziness	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		1/7 (14.3%)		1/13 (7.7%)		12/87 (13.8%)
Burning sensation	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Hypoaesthesia	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		2/13 (15.4%)		0/87 (0%)
Neuropathy peripheral	2/7 (28.6%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		8/87 (9.2%)
Peripheral sensory neuropathy	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		5/87 (5.7%)
Amnesia	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Aura	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Brain oedema	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Memory impairment	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Narcolepsy	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Paraesthesia	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Sinus headache	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Dizziness postural	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Seizure	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Tremor	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Psychiatric disorders
Insomnia	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		1/7 (14.3%)		1/13 (7.7%)		13/87 (14.9%)
Anxiety	1/7 (14.3%)		1/7 (14.3%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Depression	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Panic attack	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Renal and urinary disorders
Pollakiuria	1/7 (14.3%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Dysuria	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Haematuria	1/7 (14.3%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Micturition urgency	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Renal cyst	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Hypertonic bladder	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/7 (28.6%)		4/7 (57.1%)		3/13 (23.1%)		0/7 (0%)		3/13 (23.1%)		19/87 (21.8%)
Dyspnoea	1/7 (14.3%)		3/7 (42.9%)		2/13 (15.4%)		2/7 (28.6%)		1/13 (7.7%)		18/87 (20.7%)
Oropharyngeal pain	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Nasal congestion	0/7 (0%)		1/7 (14.3%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Dysphonia	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Haemoptysis	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Paranasal sinus discomfort	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Sinus congestion	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		6/87 (6.9%)
Upper respiratory tract congestion	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Upper-airway cough syndrome	0/7 (0%)		1/7 (14.3%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Wheezing	0/7 (0%)		0/7 (0%)		2/13 (15.4%)		2/7 (28.6%)		0/13 (0%)		6/87 (6.9%)
Dyspnoea exertional	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hypoxia	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Productive cough	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Sinus pain	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Skin and subcutaneous tissue disorders
Rash	2/7 (28.6%)		2/7 (28.6%)		3/13 (23.1%)		0/7 (0%)		1/13 (7.7%)		8/87 (9.2%)
Photosensitivity reaction	1/7 (14.3%)		1/7 (14.3%)		2/13 (15.4%)		1/7 (14.3%)		1/13 (7.7%)		10/87 (11.5%)
Pruritus	1/7 (14.3%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Rash macular	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Alopecia	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Dermatitis acneiform	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)
Dermatitis allergic	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Dry skin	1/7 (14.3%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Night sweats	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Rash maculo-papular	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		0/13 (0%)		7/87 (8%)
Social circumstances
Tanning	0/7 (0%)		0/7 (0%)		0/13 (0%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Vascular disorders
Flushing	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		1/7 (14.3%)		0/13 (0%)		0/87 (0%)
Haematoma	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Hot flush	0/7 (0%)		0/7 (0%)		1/13 (7.7%)		0/7 (0%)		0/13 (0%)		0/87 (0%)
Thrombophlebitis	0/7 (0%)		0/7 (0%)		0/13 (0%)		0/7 (0%)		1/13 (7.7%)		0/87 (0%)

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.