Trial Outcomes & Findings for Bevacizumab With Abraxane in Patients With Recurrent Ovarian/ Peritoneal Cancer (NCT NCT00407563)

NCT ID: NCT00407563

Last Updated: 2012-04-05

Results Overview

Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 48 participants
• Primary outcome timeframe: 6 months after initiation of study treatment
• Results posted on: 2012-04-05

Participant Flow

9 community oncology research sites across the US within the ACORN network participated in this study. Enrollment started in January 2007 and was completed in December 2008.

Informed consent was obtained from all subjects. All subjects underwent screening procedures to verify eligibility.

Participant milestones

Measure	Bevacizumab and Abraxane All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Overall Study STARTED	48
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Bevacizumab and Abraxane All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Overall Study Patient continues on treatment	1

Baseline Characteristics

Bevacizumab With Abraxane in Patients With Recurrent Ovarian/ Peritoneal Cancer

Baseline characteristics by cohort

Measure	Bevacizumab and Abraxane n=48 Participants All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants
Age Continuous	61.6 years STANDARD_DEVIATION 10.22 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	48 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months after initiation of study treatment

Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Outcome measures

Measure	Bevacizumab and Abraxane n=48 Participants All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
6-month Progression-Free Rate	62.5 percentage of patients Interval 47.8 to 77.2

SECONDARY outcome

Timeframe: Radiologic imaging was repeated after every 3 cycles (about every 12 weeks) during study treatment, up to 31 months.

Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.

Outcome measures

Measure	Bevacizumab and Abraxane n=48 Participants All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Best Overall Response Complete response	4 Participants
Best Overall Response Partial response	20 Participants
Best Overall Response Stable disease	14 Participants
Best Overall Response Progressive disease	8 Participants
Best Overall Response Not evaluable	2 Participants

SECONDARY outcome

Timeframe: Overall survival is defined as the time from treatment start until death from any cause, assessed up to 40 months.

Population: Participants who had not experienced death during or after stopping treatment were censored in the analysis.

Outcome measures

Measure	Bevacizumab and Abraxane n=48 Participants All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Overall Survival	17.15 Months Interval 13.57 to 23.82

SECONDARY outcome

Timeframe: PFS was measured from day 1 of treatment until time of progression (assessed every 12 weeks) or death, whichever came first, assessed up to 30 months.

Population: Participants who had not experienced either disease progression or death during or after stopping treatment were censored in the analysis.

Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Outcome measures

Measure	Bevacizumab and Abraxane n=48 Participants All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Progression-free Survival (PFS)	8.08 Months Interval 5.78 to 10.15

SECONDARY outcome

Timeframe: Assessed over 6 months of study treatment

Population: The 2 tailed, 95% confidence interval of the estimated response rate was calculated using the normal approximation to the binomial distribution.

The outcome measure assessed the percentage of participants who had achieved either a Partial or Complete Response over 6 months of treatment. Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR.

Outcome measures

Measure	Bevacizumab and Abraxane n=48 Participants All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Best Overall Response at Six Months	50 percentage of patients Interval 34.8 to 65.1

Adverse Events

Bevacizumab and Abraxane

Serious events: 13 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab and Abraxane n=48 participants at risk All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Blood and lymphatic system disorders Neutropenia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Pancytopenia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Cardiac disorders Cardio-respiratory arrest	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal distension	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Colitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Constipation	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Intestinal perforation	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Nausea	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Small intestinal obstruction	10.4% 5/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Vomiting	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Hernia obstructive	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Bronchitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Candidiasis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Gastroenteritis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Pneumonia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Overdoses	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Body temperature increased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Dehydration	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Renal failure acute	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Deep vein thrombosis	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hypotension	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.

Other adverse events

Measure	Bevacizumab and Abraxane n=48 participants at risk All subjects received treatment with bevacizumab and Abraxane. Bevacizumab will be given via IV infusion at 10 mg/kg given on days 1 and 15 of a 28-day cycle. Abraxane will be given via IV infusion at 100 mg/m\^2 over 30 minutes on days 1, 8, and 15 of a 28-day cycle.
Musculoskeletal and connective tissue disorders Foot fracture	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Groin pain	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Joint stiffness	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Anemia	20.8% 10/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Leukopenia	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Lymphadenopathy	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Lymphopenia	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Neutropenia	29.2% 14/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Blood and lymphatic system disorders Thrombocytopenia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Cardiac disorders Palpitations	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Ear and labyrinth disorders External ear pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Ear and labyrinth disorders Tinnitus	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Blepharitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Cataract	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Diplopia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Dry eye	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Erythema of eyelid	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Eye hemorrhage	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Lacrimation increased	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Photopsia	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Eye disorders Vision blurred	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal distension	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain	22.9% 11/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain lower	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Abdominal pain upper	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Ascites	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Colitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Constipation	33.3% 16/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Diarrhea	33.3% 16/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dry mouth	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Dyspepsia	10.4% 5/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Feces hard	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Gingival pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Glossodynia	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Hemorrhoids	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Nausea	37.5% 18/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Oral pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Paresthesia oral	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Peritoneal and retroperitoneal disorders	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Proctalgia	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Rectal hemorrhage	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Reflux gastritis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Small intestinal obstruction	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Sore mouth	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Stomatitis	22.9% 11/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Toothache	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Gastrointestinal disorders Vomiting	29.2% 14/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Asthenia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Catheter site inflammation	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chest pain	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Chills	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Fatigue	77.1% 37/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Inflammation	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Influenza like illness	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Injection site reaction	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Local swelling	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Localized edema	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Malaise	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Nodule	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Edema peripheral	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Pain	10.4% 5/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
General disorders Pyrexia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Hepatobiliary disorders Hepatic pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Hepatobiliary disorders Hepatomegaly	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Immune system disorders Hypersensitivity	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Immune system disorders Multiple allergies	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Bronchitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Candidiasis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Catheter site infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Cellulitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Device related infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Fungal infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Gastroenteritis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Hand-foot-and-mouth disease	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Laryngitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Localized infection	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Nasopharyngitis	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Oral herpes	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Pharyngitis streptococcal	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Postpoperative wound infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Rhinitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Sepsis syndrome	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Sialoadenitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Sinusitis	14.6% 7/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Streptococcal infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Tooth infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Upper respiratory tract infection	16.7% 8/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Urinary tract infection	22.9% 11/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Vaginal infection	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Vaginitis bacterial	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Infections and infestations Wound infection	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Chest injury	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Contusion	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Joint sprain	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Post procedural hemorrhage	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Postoperative ileus	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Procedural pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Procedural site reaction	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Injury, poisoning and procedural complications Skin laceration	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Aspartate aminotransferase increased	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood creatinine increased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood lactate dehydrogenase increased	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood pressure increased	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Blood thyroid stimulating hormone increased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Body temperature increased	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations C-reactive protein increased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations CD4 lymphocytes increased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Forced expiratory volume	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Hematocrit decreased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Hemoglobin decreased	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Monoctye count increased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Neutrophil count decreased	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Parasite stool test positive	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Platelet count decreased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations Red blood cell count decreased	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Investigations White blood cell count decreased	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Decreased appetite	16.7% 8/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Dehydration	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Fluid retention	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypercalcemia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyperglycemia	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyperkalemia	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypermagnesemia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypernatremia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hyperphosphatemia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypoglycemia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypokalemia	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypomagnesemia	12.5% 6/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Hypophosphatemia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Metabolism and nutrition disorders Weight loss poor	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Arthralgia	29.2% 14/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Arthritis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Back pain	10.4% 5/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Flank pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Joint swelling	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Muscle spasms	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Muscular weakness	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Myalgia	12.5% 6/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Osteoporosis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	18.8% 9/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Plantar fasciitis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumor benign	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dizziness	10.4% 5/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Dysgeusia	14.6% 7/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Encephalopathy	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Headache	25.0% 12/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Hypoesthesia	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Memory impairment	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Nerve compression	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Neuralgia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Neuropathy peripheral	31.2% 15/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Paresthesia	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Sciatica	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Nervous system disorders Sinus headache	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Anxiety	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Depression	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Disturbance in attention	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Insomnia	18.8% 9/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Mood altered	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Psychiatric disorders Nightmare	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Dysuria	12.5% 6/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Hematuria	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Micturition urgency	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Proteinuria	12.5% 6/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Renal and urinary disorders Urethral pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Breast pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Edema genital	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Pelvic pain	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Sexual dysfunction	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Vaginal discharge	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Vaginal hemorrhage	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Vulvovaginal dryness	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Reproductive system and breast disorders Vulvovaginal pruritis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Asthma	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Cough	22.9% 11/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dysphonia	18.8% 9/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dyspnea	20.8% 10/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Dyspnea exertional	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Epistaxis	47.9% 23/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Hemoptysis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.4% 5/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Postnasal drip	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	12.5% 6/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Sinus congestion	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Sinus disorder	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Respiratory, thoracic and mediastinal disorders Sinus disorder, NOS	4.2% 2/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Acne	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Alopecia	31.2% 15/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Blister	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Dermatitis acneiform	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Dry skin	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Nail discoloration	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Nail disorder	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Onychomadesis	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Pruritus	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Rash	8.3% 4/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Skin discoloration	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Skin disorder	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Skin and subcutaneous tissue disorders Umbilical hemorrhage	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Surgical and medical procedures Ileostomy	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Surgical and medical procedures Tooth extraction	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Flushing	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hot flush	2.1% 1/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hypertension	20.8% 10/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.
Vascular disorders Hypotension	6.2% 3/48 • Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment, up to 32 months. Systematic Assessment - subjects were assessed for adverse events weekly by either the research coordinator, treating physician, or other appropriate sub-investigator.

Additional Information

Vice President of Scientific Affairs

Accelerated Community Oncology Research Network, Inc.

Phone: 901-435-5570

Email: mwalker@acorncro.com

Results disclosure agreements

• Principal investigator is a sponsor employee Proposed publication must be submitted to Funder at least 60 days prior to the submission for publication. If Funder requests in writing, the proposed publication may be held for an additional 90 days.
• Publication restrictions are in place

Restriction type: OTHER