Trial Outcomes & Findings for Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS) (NCT NCT00948064)

Last Updated: 2020-02-24

Results Overview

Assessment of survival for outcome done on 60 days following therapy and includes participants alive for at least 60 days. Survival is calculated from start of therapy until death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

110 participants

Primary outcome timeframe

Phase I, Baseline to 60 days following first treatment.

Results posted on

2020-02-24

Participant Flow

Recruitment Period: September 08, 2009 to March 20, 2014. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Of the 110 participants enrolled, 31 were enrolled in the Phase I portion of the study and 79 were enrolled in Phase II part of the study.

Participant milestones

Participant milestones
Measure	Vorinostat With Azacitidine, Phase I Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Phase I STARTED	31	0	0
Phase I COMPLETED	30	0	0
Phase I NOT COMPLETED	1	0	0
Phase II STARTED	0	52	27
Phase II COMPLETED	0	51	26
Phase II NOT COMPLETED	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Vorinostat With Azacitidine, Phase I Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Phase I No treatment received	1	0	0
Phase II Physician Decision	0	0	1
Phase II Withdrawal by Subject	0	1	0

Baseline Characteristics

Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vorinostat With Azacitidine, Phase I n=31 Participants Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II n=52 Participants Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II n=27 Participants Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Total n=110 Participants Total of all reporting groups
Age, Continuous	74 years n=5 Participants	71 years n=7 Participants	71 years n=5 Participants	72 years n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	15 Participants n=7 Participants	9 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	37 Participants n=7 Participants	18 Participants n=5 Participants	77 Participants n=4 Participants
Region of Enrollment United States	31 participants n=5 Participants	52 participants n=7 Participants	27 participants n=5 Participants	110 participants n=4 Participants

PRIMARY outcome

Timeframe: Phase I, Baseline to 60 days following first treatment.

Population: Of the 31 enrolled participants, 30 were evaluable and 1 participant never received treatment.

Assessment of survival for outcome done on 60 days following therapy and includes participants alive for at least 60 days. Survival is calculated from start of therapy until death from any cause.

Outcome measures

Outcome measures
Measure	Vorinostat With Azacitidine, Phase I n=30 Participants Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Survival at Day 60	24 participants	—	—

PRIMARY outcome

Timeframe: 12-18 Months

Population: Out of 79 participants enrolled in Phase II, 2 participants were not evaluable - 1 participant was removed from study per treating physician discretion and the other was removed per participant's request.

Number of participants with Complete Response (CR) in AML requiring disappearance of all signs and symptoms related to disease, normalization of peripheral counts (absolute neutrophil count 10\^9/L or more, platelet count 100 x 10\^9/L or more), and a marrow with 5% or less marrow blasts; a hematologic improvement (HI) defined as a CR except for a platelet count increase by 50% to above 30 x 10\^9/L. For MDS, the International Working Group criteria used to assess response.

Outcome measures

Outcome measures
Measure	Vorinostat With Azacitidine, Phase I n=30 Participants Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II n=51 Participants Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II n=26 Participants Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Response Rate Complete Response	9 participants	11 participants	8 participants
Response Rate Hematologic Improvement	0 participants	1 participants	1 participants
Response Rate No Response	21 participants	39 participants	17 participants
Response Rate Not Evaluable	0 participants	1 participants	1 participants

PRIMARY outcome

Timeframe: Phase II, Baseline to 60 days following first treatment.

Population: Of the 79 participants enrolled, 78 were evaluable and 1 participant withdrew from study.

Assessment of survival for outcome done on 60 days following therapy and includes participants alive for at least 60 days. Survival is calculated from start of therapy until death from any cause.

Outcome measures

Outcome measures
Measure	Vorinostat With Azacitidine, Phase I n=51 Participants Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II n=27 Participants Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Survival at Day 60	43 participants	18 participants	—

Adverse Events

Vorinostat With Azacitidine, Phase I

Serious events: 15 serious events

Other events: 21 other events

Deaths: 0 deaths

Vorinostat With Azacitidine, Phase II

Serious events: 36 serious events

Other events: 45 other events

Deaths: 0 deaths

Azacitidine, Phase II

Serious events: 18 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Guillermo Garcia-Manero, MD/Professor, Leukemia Department

University of Texas (UT) MD Anderson Cancer Center

Phone: 713-745-3428

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Vorinostat With Azacitidine, Phase I n=30 participants at risk Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II n=52 participants at risk Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II n=27 participants at risk Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Infections and infestations Sinusitis	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Renal and urinary disorders Acute Renal Failure	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	11.1% 3/27 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Clostridium Difficile Colitis	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Death	26.7% 8/30 • Number of events 8 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	21.2% 11/52 • Number of events 11 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	22.2% 6/27 • Number of events 6 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Dehydration	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Diarrhea	10.0% 3/30 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Blood and lymphatic system disorders Hemoptysis	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Metabolism and nutrition disorders Hyperglycemia	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Cardiac disorders Hypotension	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Infection Pneumonia	10.0% 3/30 • Number of events 4 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Infection Pseudomonas Bacteremia	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Cardiac disorders Left Ventricular Systolic Dysfunction	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Muscle Weakness	6.7% 2/30 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Nausea	6.7% 2/30 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Vomiting	6.7% 2/30 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Neutropenic Fever	13.3% 4/30 • Number of events 6 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	17.3% 9/52 • Number of events 14 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	18.5% 5/27 • Number of events 7 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Renal and urinary disorders Renal Failure	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Seizures	3.3% 1/30 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Stroke	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Cardiac disorders Supraventricular Arrythmia	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Abdominal Pain	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Acute Maxillary Sinusitis	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Renal and urinary disorders Acute Renal Insufficiency	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Altered Mental Status	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Anal Fistula	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Cardiac disorders Atrial Fibrillation	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Back Pain	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	7.7% 4/52 • Number of events 4 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Eye disorders Blurry Vision	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Cellulitis	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Chest Pain	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Colitis	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Constipation	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Cerebrovascular Accident	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Surgical and medical procedures Debridement of Anal Wound and Laproscopic Placement of Colostomy	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Diverticulitis	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Dizziness	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Vascular disorders Deep Vein Thrombosis of Upper Extremity at PICC Site	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Metabolism and nutrition disorders Elevated Bilirubin	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.

Other adverse events
Measure	Vorinostat With Azacitidine, Phase I n=30 participants at risk Open-Label: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three times a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 6 weeks.	Vorinostat With Azacitidine, Phase II n=52 participants at risk Randomized, ARM A: Azacitidine 75 mg/m\^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.	Azacitidine, Phase II n=27 participants at risk Randomized, ARM B: Azacitidine 75 mg/m\^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
Metabolism and nutrition disorders Alanine Transaminase (ALT)	3.3% 1/30 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Metabolism and nutrition disorders Bilirubin	6.7% 2/30 • Number of events 5 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Constipation	23.3% 7/30 • Number of events 10 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	32.7% 17/52 • Number of events 44 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	22.2% 6/27 • Number of events 13 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Metabolism and nutrition disorders Creatinine	6.7% 2/30 • Number of events 5 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Diarrhea	6.7% 2/30 • Number of events 6 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	26.9% 14/52 • Number of events 20 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Fatigue	13.3% 4/30 • Number of events 4 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	65.4% 34/52 • Number of events 87 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	44.4% 12/27 • Number of events 20 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Neutropenic Fever	10.0% 3/30 • Number of events 8 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	15.4% 8/52 • Number of events 13 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	7.4% 2/27 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Skin and subcutaneous tissue disorders Hair Loss/Alopecia	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Respiratory, thoracic and mediastinal disorders Hiccoughs	3.3% 1/30 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Infection	16.7% 5/30 • Number of events 7 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Mucositis/Stomatitis	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Muscle Weakness	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	19.2% 10/52 • Number of events 16 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Nausea	20.0% 6/30 • Number of events 6 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	38.5% 20/52 • Number of events 40 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	7.4% 2/27 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Infections and infestations Opportunistic Infection	6.7% 2/30 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	7.4% 2/27 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-Other	3.3% 1/30 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Skin and subcutaneous tissue disorders Rash/Desquamation	6.7% 2/30 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Vomiting	6.7% 2/30 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 4 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Colitis	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Insomnia	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Pain	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 8 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	7.4% 2/27 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Renal and urinary disorders Urinary Frequency/Urgency	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/52 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.7% 1/27 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Cardiac disorders Cardiac General	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Confusion	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
General disorders Death	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Skin and subcutaneous tissue disorders Dermatology/Skin	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Dizziness	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	23.1% 12/52 • Number of events 17 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	25.0% 13/52 • Number of events 26 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Blood and lymphatic system disorders Edema	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	23.1% 12/52 • Number of events 19 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Gastrointestinal disorders Gastrointestinal	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Vascular disorders Hemorrhage/Bleeding	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Memory Impairment	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	17.3% 9/52 • Number of events 12 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Mental Status	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 3 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Neurology	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Nervous system disorders Neuropathy	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 5 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Eye disorders Occular/Visual	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Eye disorders Blurred Vision	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	5.8% 3/52 • Number of events 6 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Respiratory, thoracic and mediastinal disorders Voice Changes/Dysarthria	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	1.9% 1/52 • Number of events 1 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.
Eye disorders Watery Eye	0.00% 0/30 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	3.8% 2/52 • Number of events 2 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.	0.00% 0/27 • Adverse event collected when occur within 30 days of discontinuation of dosing or completion of participation in study if the last scheduled visit occurs at a later time. Overall study period: January 2009 to April 2015. Of the 31 participants enrolled in the phase I portion of this study, 1 participant did not receive treatment; hence only 30 participants were evaluable for serious and other adverse events.