Trial Outcomes & Findings for Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma. (NCT NCT01777776)

Last Updated: 2016-09-13

Results Overview

Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Cycle 1 (approximately 28 days)

Results posted on

2016-09-13

Participant Flow

Recruitment to CLEE011X2105 began on 10-July-2013. The study concluded on 13-April-2015. Participant Flow data is comprised of the Full Analysis Set (FAS), which is all patients who received at least one dose of LGX818 or LEE011. Not completed subjects represents subjects that stopped treatment early, due to the corresponding reason.

In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.

Participant milestones

Participant milestones
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Overall Study STARTED	6	12	6	4
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	6	12	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Overall Study Adverse Event	2	4	0	0
Overall Study Disease Progression	4	8	6	3
Overall Study Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) n=12 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) n=4 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Total n=28 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	18 Participants n=21 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	10 Participants n=21 Participants
Age, Continuous	65.0 years STANDARD_DEVIATION 10.71 • n=5 Participants	49.8 years STANDARD_DEVIATION 13.66 • n=7 Participants	58.0 years STANDARD_DEVIATION 10.55 • n=5 Participants	62.0 years STANDARD_DEVIATION 17.63 • n=4 Participants	56.6 years STANDARD_DEVIATION 13.90 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	11 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	17 Participants n=21 Participants
Weight	84.60 kilograms STANDARD_DEVIATION 12.793 • n=5 Participants	78.08 kilograms STANDARD_DEVIATION 17.069 • n=7 Participants	80.17 kilograms STANDARD_DEVIATION 10.308 • n=5 Participants	74.70 kilograms STANDARD_DEVIATION 16.415 • n=4 Participants	79.44 kilograms STANDARD_DEVIATION 14.450 • n=21 Participants
WHO/ECOG performance status 0	2 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	8 participants n=21 Participants
WHO/ECOG performance status 1	4 participants n=5 Participants	7 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	19 participants n=21 Participants
WHO/ECOG performance status 2	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: Cycle 1 (approximately 28 days)

Population: Analysis group is comprised of the Safety Set (SS), which includes all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment.

Outcome measures

Outcome measures
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) n=12 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) n=4 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 Myalagia	1 participants with DLTs	0 participants with DLTs	0 participants with DLTs	0 participants with DLTs
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 Elevated Bilirubin	1 participants with DLTs	0 participants with DLTs	0 participants with DLTs	0 participants with DLTs
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 Neuralgia	0 participants with DLTs	0 participants with DLTs	1 participants with DLTs	0 participants with DLTs
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 Maculopapular Rash	0 participants with DLTs	0 participants with DLTs	0 participants with DLTs	1 participants with DLTs

PRIMARY outcome

Timeframe: Approximately 23 months after enrollment

Population: This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.

As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Approximately 23 months after enrollment

Population: This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.

As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 23 months after enrollment

Outcome measures

Outcome measures
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) n=12 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) n=4 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).	6 participants	12 participants	6 participants	4 participants

SECONDARY outcome

Timeframe: Approximately 23 months after enrollment

Population: Analysis group is comprised of the Safety Set (SS), which is all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment.

Outcome measures

Outcome measures
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) n=12 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) n=6 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) n=4 Participants Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).	3 participants	5 participants	3 participants	1 participants

SECONDARY outcome

Timeframe: 28-day cycles

Population: This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to plasma concentration time profiles were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 23 months after enrollment

Population: This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.

ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 23 months after enrollment

Population: This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.

PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 23 months after enrollment

Population: This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.

DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 23 months after enrollment

Population: This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.

OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28-day cycles

Population: This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28-day cycles

Population: This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28-day cycles

Population: This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28-day cycles

Population: This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28-day cycles

Population: This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.

Outcome measures

Outcome data not reported

Adverse Events

Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort)

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Array BioPharma, Inc.

Phone: 303-381-6604

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) n=6 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) n=12 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) n=6 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) n=4 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Infections and infestations Pneumonia	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Injury, poisoning and procedural complications Brain oedema	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 1/4 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Musculoskeletal and connective tissue disorders Chest wall abscess	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Psychiatric disorders Confusional state	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Skin and subcutaneous tissue disorders Dermatitis bullous	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Musculoskeletal and connective tissue disorders Failure to thrive	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Nervous system disorders Memory impairment	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Psychiatric disorders Mental status changes	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Musculoskeletal and connective tissue disorders Neck pain	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Nervous system disorders Seizure	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Infections and infestations Sepsis	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Nervous system disorders Simple partial seizures	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Nervous system disorders Spinal cord compression	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Vascular disorders Syncope	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Immune system disorders Systemic inflammatory response syndrome	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Hepatobiliary disorders Transaminases increased	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Renal and urinary disorders Urinary tract infection	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.

Other adverse events
Measure	Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) n=6 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) n=12 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) n=6 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.	Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) n=4 participants at risk Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.
Eye disorders Dry eye	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Endocrine disorders Cushingoid	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Eye disorders Eye pruritus	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Eye disorders Eye discharge	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Eye disorders Vision blurred	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Eye disorders Photophobia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	33.3% 2/6 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 1/4 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	50.0% 2/4 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Neutropenia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Thrombocytopenia	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Disseminated intravascular coagulation	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Increased tendency to bruise	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Eye disorders Blepharospasm	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Leukopenia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Cardiac disorders Tachycardia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	50.0% 2/4 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Cardiac disorders Palpitations	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Ear and labyrinth disorders Ear pruritus	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Endocrine disorders Adrenal insufficiency	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Metabolism and nutrition disorders Hyperkalaemia	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 2/6 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	33.3% 4/12 • Number of events 4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 3/12 • Number of events 3 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 1/4 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Nausea	33.3% 2/6 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	50.0% 6/12 • Number of events 6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	66.7% 4/6 • Number of events 4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	100.0% 4/4 • Number of events 4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 3/12 • Number of events 3 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	50.0% 3/6 • Number of events 3 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	50.0% 2/4 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Constipation	50.0% 3/6 • Number of events 3 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 3/12 • Number of events 3 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 2/12 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	50.0% 2/4 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Stomatitis	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	33.3% 4/12 • Number of events 4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 2/12 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 2/12 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	25.0% 1/4 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Oral pain	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 2/12 • Number of events 2 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Cheilitis	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Gingival discolouration	16.7% 1/6 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/12 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Gingival ulceration	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Glossitis	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Gastrointestinal disorders Glossodynia	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	8.3% 1/12 • Number of events 1 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/6 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.	0.00% 0/4 • This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.