Trial Outcomes & Findings for Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma (NCT NCT00124657)

Last Updated: 2015-12-04

Results Overview

DLT was defined as any of the following toxicities attributable to erlotinib therapy: thrombocytopenia grade 3 and 4; neutropenia grade 4; or any grade 3 and 4 non-hematologic toxicity except for grade 3 diarrhea and grade 3 nausea and vomiting lasting ≤48 hours in participants not receiving optimal supportive therapy, grade 3 skin rash, which did not affect normal daily activities, grade 3 fever or nonneutropenic infection, grade 3 seizures, grade 3 weight gain or loss, and grade 3 transaminase elevation that returned to grade 1 or baseline within 7 days. After enrollment of the first 4 participants, grade 3 and 4 electrolyte abnormalities that resolved to ≤grade 2 within 7 days were excluded as DLT. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

62 participants

Primary outcome timeframe

During the first 8 weeks of therapy

Results posted on

2015-12-04

Participant Flow

Overall accrual included 62 unique subjects. Five subjects participated in both Phase I and Phase II. Phase I enrolled 23 (03/2005-06/2007). Phase II enrolled an additional 39 participants (08/2007-11/2010) plus 5 carried over from Phase I for a total of 44. One of the 39 accrued to Phase II was enrolled at Rady Children's Hospital.

Participants had newly diagnosed high-grade glioma (except those originating in the brain stem) and unfavorable low-grade glioma and were ≥ 3 and ≤21 years of age. Participants receiving enzyme-inducing anticonvulsants (EIACs) were not eligible for this study. Patients with spinal cord tumors were eligible for the Phase II component of this study.

Participant milestones

Participant milestones
Measure	Phase I Only 18 participants were enrolled on the Phase I portion of the trial only.	Phase I and Phase II 5 patients participated in both the Phase I portion and the Phase II portion of the study.	Phase II Only 39 participants were enrolled on the Phase II portion of the trial only.
Overall Study STARTED	18	5	39
Overall Study COMPLETED	2	0	7
Overall Study NOT COMPLETED	16	5	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Only 18 participants were enrolled on the Phase I portion of the trial only.	Phase I and Phase II 5 patients participated in both the Phase I portion and the Phase II portion of the study.	Phase II Only 39 participants were enrolled on the Phase II portion of the trial only.
Overall Study Toxicity	0	0	1
Overall Study Non-compliance	1	0	4
Overall Study Progressive disease	14	5	27
Overall Study Intercurrent illness	1	0	0

Baseline Characteristics

Erlotinib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Glioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I Only n=18 Participants 18 participants were enrolled on the Phase I portion of the trial only.	Phase I and Phase II n=5 Participants 5 patients participated in both the Phase I portion and the Phase II portion of the study.	Phase II Only n=39 Participants 39 participants were enrolled on the Phase II portion of the trial only.	Total n=62 Participants Total of all reporting groups
Age, Continuous	11.49 years STANDARD_DEVIATION 4.31 • n=5 Participants	11.47 years STANDARD_DEVIATION 6.05 • n=7 Participants	10.55 years STANDARD_DEVIATION 4.85 • n=5 Participants	11.12 years STANDARD_DEVIATION 4.81 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	2 Participants n=7 Participants	23 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants	29 Participants n=4 Participants
Diagnosis Anaplastic astrocytoma (AA)	7 participants n=5 Participants	1 participants n=7 Participants	19 participants n=5 Participants	27 participants n=4 Participants
Diagnosis Glioblastoma multiforme (GBM)	8 participants n=5 Participants	4 participants n=7 Participants	17 participants n=5 Participants	29 participants n=4 Participants
Diagnosis Anaplastic oligoastrocytoma	2 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Diagnosis Anaplastic ganglioglioma	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Diagnosis Unfavorable fibrillary astrocytoma	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Diagnosis Spinal GBM	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: During the first 8 weeks of therapy

Population: 23 participants were enrolled on Phase I component; 22 were analyzed for DLT over 4 dose levels. 1 treated at dose level 120mg/m\^2 was not assessable for DLT due to early tumor progression. 4 were treated before and 19 after the study was amended to exclude grade 3 and 4 electrolyte abnormalities that resolved to ≤ grade 2 within 7 days.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=7 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 n=3 Participants Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 n=6 Participants Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 n=6 Participants Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Number of Participants With Dose-limiting Toxicity (DLT)	0 participants	0 participants	1 participants	2 participants

PRIMARY outcome

Timeframe: During the first 8 weeks of therapy.

Population: 22 participants were analyzed for MTD over 4 dose levels. One of 23 enrolled participants was not evaluable due to early disease progression.

MTD was defined as the highest dosage level in which no more than one of six assessable participants experienced dose-limiting toxicities (DLT). The dosage of erlotinib was increased by approximately 30% in each dosage level starting at 80% of the MTD in adults with solid tumors. A traditional 3+3 dose escalation scheme was used to estimate the MTD.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=22 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Maximum Tolerated Dose (MTD) of Erlotinib	120 mg/m^2	—	—	—

PRIMARY outcome

Timeframe: 1 and 2 years after end of therapy

Population: Per protocol, 41 participants with either anaplastic astrocytoma or glioblastoma multiforme were analyzed for this outcome.

Progression-free survival (PFS) distributions for the Phase II participants with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were calculated using Kaplan-Meier estimates (n=41). PFS was defined as the interval between treatment start and initial failure, including clinical or radiologic progression or death from any cause. PFS was not calculated for the other disease types.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=8 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 n=12 Participants Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 n=20 Participants Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 n=21 Participants Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Progression Free Survival (PFS) 1-year PFS	0.75 years Standard Deviation 0.14	0.33 years Standard Deviation 0.12	0.45 years Standard Deviation 0.106	0.19 years Standard Deviation 0.077
Progression Free Survival (PFS) 2-year PFS	NA years Standard Deviation NA 2-year PFS was not done by diagnosis group for Phase I participants.	NA years Standard Deviation NA 2-year PFS was not done by diagnosis group for Phase I participants.	0.15 years Standard Deviation 0.069	0.19 years Standard Deviation 0.077

SECONDARY outcome

Timeframe: After first dose of therapy, and Day 8 of therapy

Population: Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study.

Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=7 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 n=2 Participants Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 n=5 Participants Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 n=3 Participants Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Cmax of Erlotinib and Its Metabolite OSI-420 Erlotinib, after first dose of therapy	1.3 mg/mL Interval 0.94 to 2.2	1.6 mg/mL Interval 1.3 to 1.8	1.2 mg/mL Interval 0.5 to 2.0	1.8 mg/mL Interval 1.3 to 3.0
Cmax of Erlotinib and Its Metabolite OSI-420 Erlotinib, Day 8 of therapy	1.8 mg/mL Interval 1.7 to 2.8	1.3 mg/mL Interval 1.3 to 1.3	1.4 mg/mL Interval 1.0 to 3.0	2 mg/mL Interval 1.3 to 2.4
Cmax of Erlotinib and Its Metabolite OSI-420 OSI-420, after first dose of therapy	0.13 mg/mL Interval 0.05 to 0.2	0.16 mg/mL Interval 0.12 to 0.2	0.14 mg/mL Interval 0.1 to 0.3	0.32 mg/mL Interval 0.26 to 0.33
Cmax of Erlotinib and Its Metabolite OSI-420 OSI-420, Day 8 of therapy	0.25 mg/mL Interval 0.2 to 0.6	0.17 mg/mL Interval 0.17 to 0.17	0.3 mg/mL Interval 0.1 to 0.5	0.3 mg/mL Interval 0.3 to 0.3

SECONDARY outcome

Timeframe: After first dose of therapy

Population: Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=7 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 n=2 Participants Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 n=5 Participants Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 n=3 Participants Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Erlotinib Tmax Erlotinib, after first dose of therapy	4 hours Interval 2.1 to 8.2	3.1 hours Interval 2.0 to 4.1	2.2 hours Interval 1.0 to 4.0	2.2 hours Interval 2.0 to 2.5
Erlotinib Tmax Erlotinib, Day 8 of therapy	2.1 hours Interval 1.0 to 4.1	2.6 hours Interval 1.2 to 4.0	1.75 hours Interval 1.3 to 4.0	2.2 hours Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: After first dose of therapy, and Day 8 of therapy

Population: Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=7 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 n=2 Participants Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 n=5 Participants Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 n=3 Participants Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 Erlotinib, after first dose of therapy	34.9 mg*h/mL Interval 23.1 to 52.6	23.9 mg*h/mL Interval 14.4 to 33.3	27.8 mg*h/mL Interval 18.9 to 28.8	37.1 mg*h/mL Interval 33.1 to 50.6
AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 Erlotinib, Day 8 of therapy	28.8 mg*h/mL Interval 21.8 to 30.9	21.2 mg*h/mL Interval 18.1 to 24.2	23.1 mg*h/mL Interval 11.8 to 51.2	35.5 mg*h/mL Interval 23.7 to 51.0
AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 OSI-420, after first dose of therapy	2.1 mg*h/mL Interval 1.2 to 3.3	1.9 mg*h/mL Interval 1.4 to 2.3	2.5 mg*h/mL Interval 1.7 to 2.7	4.2 mg*h/mL Interval 4.1 to 5.2
AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 OSI-420, Day 8 of therapy	3.3 mg*h/mL Interval 2.0 to 6.9	2.1 mg*h/mL Interval 1.7 to 2.4	2.8 mg*h/mL Interval 1.9 to 5.9	4.3 mg*h/mL Interval 3.8 to 6.1

SECONDARY outcome

Timeframe: Once at tumor resection and diagnosis

Population: Unstained slides were available for immunohistochemistry analysis in 21 of the 23 Phase I participants.

Statistical analyses of genomic changes, expression profiles and validation studies should be considered in an exploratory and hypothesis-generating context. Fresh frozen tumor tissue was obtained at the time of tumor resection and diagnosis. DNA was extracted from formalin-fixed, paraffin-embedded tissue. The entire PTEN coding sequence (exons 1-9), exons 1, 9 and 20 of PIK3CA, and exons 17-24 of EGFR were evaluated using exon-specific PCR amplification, and immunohistochemistry was done. Tumor lesions were considered positive if \>25% cells were immunoreactive.

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=21 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Number of Positive Mutations of EGFR and Downstream Pathways Positive for PTEN (R130*)	1 participants	—	—	—
Number of Positive Mutations of EGFR and Downstream Pathways Positive PIK3CA (H1047R)	1 participants	—	—	—
Number of Positive Mutations of EGFR and Downstream Pathways Positive EGFR kinase domain	0 participants	—	—	—

SECONDARY outcome

Timeframe: 5 Years

Population: This outcome was not assessed due to insufficient availability of tumor and control samples for analysis.

The objective was to test the ability of erlotinib to inhibit the EGFR signaling in patients with high-grade glioma who required a second surgery. This outcome was not assessed due to insufficient availability of tumor and control samples for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at diagnosis and regular intervals during therapy (up to 2 years after start of therapy)

Population: This objective became obsolete over the course of the protocol, and data was not collected.

This objective was to prospectively investigate the correlation between standard magnetic resonance imaging (MRI) and investigational radiologic techniques (MR spectroscopy, perfusion/diffusion, PET scan, DEMRI/BLAST) in assessing tumor response to this treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 Years

Population: This objective became obsolete over the course of the protocol, and data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at diagnosis and regular intervals during therapy (up to 2 years after start of therapy)

Population: This objective became obsolete over the course of the protocol, and data was not collected.

This objective was to determine the plasma and CSF levels of the VEGF, bFGF, and SDF1 at diagnosis, and the plasma levels of these factors at regular intervals during therapy, and to analyze the association of these results with tumor response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of therapy through 2 years.

Population: All 44 Phase II participants were evaluated. Eight of 16 participants with lymphopenia received dexamethasone within 4 weeks of the recorded toxicity. In both participants with headache, there was a documented progressive disease within 3 days of the recorded headache.

Adverse events were collected systematically for each of the 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).

Outcome measures

Outcome measures
Measure	70 mg/m^2 n=44 Participants Dose level 1 was 70 mg/m\^2, range of actual dosage was 68-83 mg/m\^2.	90 mg/m^2 n=44 Participants Dose level 2 was 90 mg/m\^2, range of actual dosage was 85-87.5 mg/m\^2.	120 mg/m^2 Dose level 3 was 120 mg/m\^2, range of actual dosage was 107-128 mg/m\^2.	160 mg/m^2 Dose level 4 was 160 mg/m\^2, range of actual dosage was 151.5-167 mg/m\^2.
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Blood: Hemoglobin	2 Participants	1 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Blood: Lymphopenia	7 Participants	8 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Blood: Neutrophils	2 Participants	1 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Blood: Platelets	0 Participants	1 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Dermatologic: Pruritus	3 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Dermatologic: Rash/Desquamation	1 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Dermatologic: Rash/acne	2 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Gastrointestinal: Anorexia	3 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Gastrointestinal: Diarrhea	5 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Gastrointestinal: Dysphagia	1 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Gastrointestinal: Mucositis	1 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Gastrointestinal: Nausea	2 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Gastrointestinal: Vomiting	4 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Metabolic: ALT/AST	2 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Metabolic: Hypokalemia	2 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Metabolic: Bilirubin	1 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Pain: Headache	1 Participants	1 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Constitutional: Fatigue	1 Participants	0 Participants	—	—
Number of Participants Experiencing Grade 3 or 4 Toxicity Events Constitutional: Weight Loss	2 Participants	0 Participants	—	—

Adverse Events

70 mg/m^2 (Phase I)

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

90 mg/m^2 (Phase I)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

120 mg/m^2 (Phase I)

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

160 mg/m^2 (Phase I)

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II

Serious events: 26 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	70 mg/m^2 (Phase I) n=7 participants at risk Participants received dose of 70 mg/m\^2, range of actual dose was 68-83 mg/m\^2.	90 mg/m^2 (Phase I) n=3 participants at risk Participants received dose of 90 mg/m\^2, range of actual dose was 85-87.5 mg/m\^2.	120 mg/m^2 (Phase I) n=7 participants at risk Participants received dose of 120 mg/m\^2, range of actual dose was 107-128 mg/m\^2.	160 mg/m^2 (Phase I) n=6 participants at risk Participants received dose of 160 mg/m\^2, range of actual dose was 151.5-167 mg/m\^2.	Phase II n=44 participants at risk Phase II participants received 120 mg/m\^2.
Blood and lymphatic system disorders Hemoglobin	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Lymphopenia	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	36.4% 16/44 • Number of events 32 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Neutrophils	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Platelets	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Fatigue	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Weight loss	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Pruritis	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Rash/Desquamation	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Rash/Acne	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Anorexia	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Diarrhea	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Dysphagia	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Mucositis	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Nausea	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Vomiting	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders ALT/AST	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Hypokalemia	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Bilirubin	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Headache	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Lipase	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Hypophosphatemia	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).

Other adverse events

Other adverse events
Measure	70 mg/m^2 (Phase I) n=7 participants at risk Participants received dose of 70 mg/m\^2, range of actual dose was 68-83 mg/m\^2.	90 mg/m^2 (Phase I) n=3 participants at risk Participants received dose of 90 mg/m\^2, range of actual dose was 85-87.5 mg/m\^2.	120 mg/m^2 (Phase I) n=7 participants at risk Participants received dose of 120 mg/m\^2, range of actual dose was 107-128 mg/m\^2.	160 mg/m^2 (Phase I) n=6 participants at risk Participants received dose of 160 mg/m\^2, range of actual dose was 151.5-167 mg/m\^2.	Phase II n=44 participants at risk Phase II participants received 120 mg/m\^2.
Skin and subcutaneous tissue disorders Nail changes	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	15.9% 7/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Pruritus/itching	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	36.4% 16/44 • Number of events 21 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Rash/desquamation	71.4% 5/7 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	57.1% 4/7 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	43.2% 19/44 • Number of events 27 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Rash: acne/acneiform	85.7% 6/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 3/3 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	71.4% 5/7 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	40.9% 18/44 • Number of events 29 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Striae	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 11 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Ear and labyrinth disorders Hearing: patients wihtout baseline audiogram and not enrolled in a monitoring program	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Ear and labyrinth disorders Otitis, external ear (non-infectious)	14.3% 1/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Hemoglobin	85.7% 6/7 • Number of events 15 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	40.9% 18/44 • Number of events 41 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Leukocytes (total WBC)	57.1% 4/7 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	71.4% 5/7 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	47.7% 21/44 • Number of events 38 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Lymphopenia	100.0% 7/7 • Number of events 18 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 3/3 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 7/7 • Number of events 14 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 6/6 • Number of events 13 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	61.4% 27/44 • Number of events 104 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	28.6% 2/7 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	22.7% 10/44 • Number of events 16 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Platelets	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Cardiac disorders Supraventricular and nodal arrhythmia, sinus tachycardia	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Cardiac disorders Hypertension	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	13.6% 6/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Cardiac disorders Hypotension	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Fatigue (asthenia, lethargy, malaise)	71.4% 5/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	40.9% 18/44 • Number of events 25 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Fever (in absence of neutrophenia defined as ANC <1.0 x 10e9/L)	71.4% 5/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Insomnia	14.3% 1/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Weight loss	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	43.2% 19/44 • Number of events 27 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Chelitis	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Dermatology/Skin - other	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 14 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Dry skin	57.1% 4/7 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	40.9% 18/44 • Number of events 19 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	85.7% 6/7 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	29.5% 13/44 • Number of events 14 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Hyperpigmentation	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Endocrine disorders Cushingoid appearance(e.g. moon face, buffalo hump, centripetal obesity, cutaneous striae)	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Anorexia	57.1% 4/7 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	83.3% 5/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	59.1% 26/44 • Number of events 30 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Constipation	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 11 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Dehydration	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	15.9% 7/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Diarrhea	85.7% 6/7 • Number of events 13 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 3/3 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 7/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	63.6% 28/44 • Number of events 51 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Gastrointestinal - Other	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 12 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Heartburn/dyspepsia	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Mucositis/stomatitis (clinical exam), oral cavity	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 3/3 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic), oral cavity	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Nausea	85.7% 6/7 • Number of events 11 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	43.2% 19/44 • Number of events 27 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Taste alteration (dysgeusia)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Vomiting	71.4% 5/7 • Number of events 13 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	43.2% 19/44 • Number of events 31 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Vascular disorders Hemorrhage, pulmonary/upper respiratory, nose	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection - Other	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	43.2% 19/44 • Number of events 26 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neurophils, external ear (otitis externa)	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, middle ear (otitis media)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, upper airway NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Opportunistic infection associated with >=Grade 2 lymphopenia	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Edema: limb	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 3/3 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	31.8% 14/44 • Number of events 26 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders AST, SGOT (serum glutamic oxaloacetic transaminase)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	29.5% 13/44 • Number of events 20 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	57.1% 4/7 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	25.0% 11/44 • Number of events 19 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Alkaline phosphatase	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Bicarbonate, serum-low	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	57.1% 4/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	36.4% 16/44 • Number of events 25 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	57.1% 4/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	15.9% 7/44 • Number of events 12 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Creatinine	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	85.7% 6/7 • Number of events 13 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	29.5% 13/44 • Number of events 23 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 14 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	85.7% 6/7 • Number of events 13 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	20.5% 9/44 • Number of events 15 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	85.7% 6/7 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	27.3% 12/44 • Number of events 22 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	71.4% 5/7 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	27.3% 12/44 • Number of events 23 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Musculoskeletal and connective tissue disorders Musculoskeletal/soft tissue - other	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Ataxia (incoordination)	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 13 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Dizziness	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Mood alteration, anxiety	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	11.4% 5/44 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Mood alteration, depression	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	13.6% 6/44 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Neurology - other	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	18.2% 8/44 • Number of events 12 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Neuropathy: motor	42.9% 3/7 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Seizure	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	57.1% 4/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	25.0% 11/44 • Number of events 25 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Speech impairment (e.g., dysphasia or aphasia)	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Tremor	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Nystagmus	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Ocular/visual - other	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	22.7% 10/44 • Number of events 11 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Ophthalmoplegia/diplopia (double vision)	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Vision-blurred vision	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Respiratory, thoracic and mediastinal disorders Cough	85.7% 6/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	15.9% 7/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain - other	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	25.0% 11/44 • Number of events 17 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, abdomen NOS	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	13.6% 6/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, back	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	9.1% 4/44 • Number of events 5 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, head/headache	71.4% 5/7 • Number of events 17 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	42.9% 3/7 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	83.3% 5/6 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	45.5% 20/44 • Number of events 29 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, throat/pharynx/larynx	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	15.9% 7/44 • Number of events 7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	57.1% 4/7 • Number of events 10 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	34.1% 15/44 • Number of events 28 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	6.8% 3/44 • Number of events 6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Ear and labyrinth disorders Auditory/Ear - other	71.4% 5/7 • Number of events 8 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Ear and labyrinth disorders Otitis, middle ear (non-infectious	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Rigors/chills	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Flushing	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Ulceration	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	100.0% 3/3 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Dental: teeth	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Vascular disorders Hemorrhage, CNS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Vascular disorders Hemorrhage, GU, urinary NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, Anal/perianal	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, eye NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, mucosa	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, pharynx	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, sinus	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, skin (cellulitis)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, urinary tract NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, wound	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	50.0% 3/6 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Musculoskeletal and connective tissue disorders Extremity-lower (gait/walking)	42.9% 3/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Cognitive disturbance	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Memory impairment	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Personality/behavioral	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Somnolence/depressed level of consciousness	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Syncope (fainting)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Ocular surface disease	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 4/6 • Number of events 4 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Vision-photophobia	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, chest/thorax NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, external ear	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	66.7% 2/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, eye	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, joint	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	28.6% 2/7 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	57.1% 4/7 • Number of events 9 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Renal and urinary disorders Urinary retention (including neurogenic bladder)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	28.6% 2/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, lip/perioral	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 2/6 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Ear and labyrinth disorders Tinnitus	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Cardiac disorders Supraventricular and nodal arrhythmia, sinus bradycardia	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Weight gain	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Bruising (in absence of Grade 3 or 4 thrombocytopenia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Burn	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Skin and subcutaneous tissue disorders Rash: dermatitis associated with radiation, radiation	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Injury, poisoning and procedural complications Death not associated with CTCAE term, disease progression NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Dysphagia (difficulty swallowing)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Flatulence	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Gastritis (including bile reflex gastritis)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Gastrointestinal disorders Ulcer, GI, stomach	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Hepatobiliary disorders Hepatobiliary/pancreas - other	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, conjunctiva	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, dental-tooth	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, Foreign body	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, lung (pnemonia)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, meninges (meningitis)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, nose	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, oral cavity-gums (gingivitis)	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, rectum	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Amylase	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Cholesterol, serum-high (hypercholestremia)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Lipase	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Metabolism and nutrition disorders Metabolic/laboratory - other	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy), whole body/generalized	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Musculoskeletal and connective tissue disorders Trismus (difficulty, restriction or pain when opening mouth)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Hydrocephalus	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Leak, cerebrospinal fluid (CSF)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Mood alteration, agitation	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Neuropathy: cranial, CN VI Lateral deviation of eye	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Neuropathy: cranial, CN VII motor-face: sensory-taste	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Neuropathy: cranial, CN VIII hearing and balance	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Neuropathy: sensory	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Psychosis (hallucinations/delusions)	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Nervous system disorders Pyramidal tract dysfunction	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Cataract	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Dry eye syndrome	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Eye disorders Eyelid dysfunction	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Respiratory, thoracic and mediastinal disorders Pulmonary/upper respiratory - other	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Renal and urinary disorders Cystitis	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	2.3% 1/44 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Renal and urinary disorders Urinary frequency/urgency	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary malignancy - possibly related to cancer treatment	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Reproductive system and breast disorders Sexual/reproductive function - other	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Injury, poisoning and procedural complications Intra-operative injury, brain	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Flu-like syndrome	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, extremity-limb	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	16.7% 1/6 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, muscle	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, oral cavity	14.3% 1/7 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, pain NOS	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
General disorders Pain, stomach	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 2 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Cardiac disorders Palpitations	14.3% 1/7 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	4.5% 2/44 • Number of events 3 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
Blood and lymphatic system disorders Lymphatics - other	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	33.3% 1/3 • Number of events 1 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/7 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/6 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).	0.00% 0/44 • Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).

Additional Information

Alberto Broniscer, MD

St. Jude Children's Research Hospital

Phone: 866-966-5934

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place