Trial Outcomes & Findings for PU-H71 in Patients With Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma That Have Not Responded to Standard Treatment (NCT NCT01581541)

Last Updated: 2017-10-04

Results Overview

A DLT was defined as an adverse event that occurred during cycle 1, was thought to be related to study drug administration, and met one of the following criteria: grade ≥ 3 non-hematologic toxicities (except diarrhea, nausea, vomiting without maximal supportive therapy; alopecia), grade 4 hematologic toxicities (except lymphopenia), and grade 2 ocular toxicity that did not resolve to ≤ grade 1 within 2 weeks. Occurrence of a DLT resulted in a dose reduction following resolution to grade ≤ 2. No more than 2 dose reductions were allowed per patient on study.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

Cycle 1 (21 days)

Results posted on

2017-10-04

Participant Flow

Participant milestones

Participant milestones
Measure	PU-H71, 10 mg/m^2 PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Overall Study STARTED	1	1	1	1	2	3	1	2	1	3	1
Overall Study COMPLETED	1	1	1	1	2	3	1	2	1	3	1
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PU-H71 in Patients With Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma That Have Not Responded to Standard Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PU-H71 n=17 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Age, Continuous	59 years n=93 Participants
Sex: Female, Male Female	7 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants
Race (NIH/OMB) White	11 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Region of Enrollment United States	17 participants n=93 Participants
Number of Prior Therapies	7 prior therapies n=93 Participants
Diagnosis Malignant Hürthle cell tumor	1 Participants n=93 Participants
Diagnosis Rectal adenocarcinoma	1 Participants n=93 Participants
Diagnosis Adenocarcinoma, not otherwise specified	6 Participants n=93 Participants
Diagnosis Adenoid cystic carcinoma	1 Participants n=93 Participants
Diagnosis Invasive poorly differentiated carcinoma	1 Participants n=93 Participants
Diagnosis Metastatic adenocarcinoma	1 Participants n=93 Participants
Diagnosis Hepatocellular carcinoma	1 Participants n=93 Participants
Diagnosis Carcinoid tumor	1 Participants n=93 Participants
Diagnosis Squamous cell carcinoma of the esophagus	1 Participants n=93 Participants
Diagnosis Synovial sarcoma	2 Participants n=93 Participants
Diagnosis Non-small cell lung cancer	1 Participants n=93 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 3 years and two months and 11 days

Severity of adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1 Mild adverse event (AE), Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, and Grade 5 Death related to AE.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Lymphopenia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Nausea	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Anemia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Aspartate Aminotransferase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Atrioventricular Block First Degree	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Blood Bilirubin Increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Fatigue	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Headache	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 2 Sinus Bradycardia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Grade 3 Vomiting	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

The MTD is the dose level at which no more than 1 of 6 patients experience DLT during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) patients have DLT as a result of the drug.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=17 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Maximum Tolerated Dose (MTD) of PU-H71	NA mg/m^2 Due to cessation of the drug supply, patients could not be accrued at higher doses, and the MTD could not be determined.	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and every 6 weeks up to 18 weeks

Population: All participants who continued further treatment and did not start an alternative treatment were considered evaluable for response.

Number of Participants According to Best Response Per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by computed tomography (CT): Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Complete Response	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Partial Response	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Stable Disease	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Progression of Disease	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: up to 126 days

Population: All participants who continued further treatment and did not start an alternative treatment were considered evaluable for response.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Number of Days on Treatment	42 days Interval 42.0 to 42.0	42 days Interval 42.0 to 42.0	42 days Interval 42.0 to 42.0	84 days Interval 84.0 to 84.0	42 days Interval 42.0 to 42.0	126 days Interval 42.0 to 126.0	84 days Interval 84.0 to 84.0	84 days Interval 84.0 to 84.0	63 days Interval 63.0 to 63.0	42 days Interval 42.0 to 42.0	42 days Interval 42.0 to 42.0

SECONDARY outcome

Timeframe: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.

The maximum concentration (Cmax) was determined by visual inspection of the concentration versus time data.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Maximum Observed Plasma Concentration (Cmax)	0.2 µM Standard Deviation 0	0.3 µM Standard Deviation 0	74.7 µM Standard Deviation 0	1.3 µM Standard Deviation 0	5.17 µM Standard Deviation 0.1	7.3 µM Standard Deviation 2.4	8.7 µM Standard Deviation 0	8.0 µM Standard Deviation 4.5	7.8 µM Standard Deviation 0	17.3 µM Standard Deviation 8.5	33.7 µM Standard Deviation 0

SECONDARY outcome

The terminal half-life (t1/2) was derived from the plasma concentration vs. time data.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Terminal Half-life (T1/2)	2.7 hours Standard Deviation 0	10.5 hours Standard Deviation 0	9.2 hours Standard Deviation 0	6.1 hours Standard Deviation 0	6.7 hours Standard Deviation 0.1	7.6 hours Standard Deviation 0.2	7.2 hours Standard Deviation 0	7.1 hours Standard Deviation 0.5	10.2 hours Standard Deviation 0	11.5 hours Standard Deviation 7.3	10.8 hours Standard Deviation 0

SECONDARY outcome

Area Under the Concentration-Time Curve From Time 0 to 24 Hours was estimated by trapezoidal rule calculations

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Area Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)]	27 µM*min Standard Deviation 0	74 µM*min Standard Deviation 0	3845 µM*min Standard Deviation 0	273 µM*min Standard Deviation 0	899 µM*min Standard Deviation 32	1186 µM*min Standard Deviation 481	1534 µM*min Standard Deviation 0	2090 µM*min Standard Deviation 459	3596 µM*min Standard Deviation 0	6866 µM*min Standard Deviation 2876	8568 µM*min Standard Deviation 0

SECONDARY outcome

Area Under the Concentration-Time Curve From Time 0 to Infinity was estimated by trapezoidal rule calculations

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)]	31 µM*min Standard Deviation 0	100 µM*min Standard Deviation 0	3905 µM*min Standard Deviation 0	301 µM*min Standard Deviation 0	1007 µM*min Standard Deviation 32	1375 µM*min Standard Deviation 591	1771 µM*min Standard Deviation 0	2477 µM*min Standard Deviation 429	5449 µM*min Standard Deviation 0	10815 µM*min Standard Deviation 5499	12151 µM*min Standard Deviation 0

SECONDARY outcome

Timeframe: Every void post-treatment on day 1 of cycle 1

Elimination of the drug was investigated by analysis of an aliquot of the total urine collected in 24 h.

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Urinary Excretion (%)	5.5 percent of dose recovered Standard Deviation 0	NA percent of dose recovered Standard Deviation NA Data were not collected from the single participant at this dose level.	1.9 percent of dose recovered Standard Deviation 0	8.8 percent of dose recovered Standard Deviation 0	6.7 percent of dose recovered Standard Deviation 1.3	6.7 percent of dose recovered Standard Deviation 4.6	8.1 percent of dose recovered Standard Deviation 0	6.0 percent of dose recovered Standard Deviation 4.2	5.4 percent of dose recovered Standard Deviation 0	8.6 percent of dose recovered Standard Deviation 4.6	5.7 percent of dose recovered Standard Deviation 0

SECONDARY outcome

Clearance was calculated from drug dose and AUC(0-∞).

Outcome measures

Outcome measures
Measure	PU-H71, 10 mg/m^2 n=1 Participants PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 Participants PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Clearance	1.03 L/h/kg Standard Deviation 0	0.63 L/h/kg Standard Deviation 0	0.03 L/h/kg Standard Deviation 0	0.63 L/h/kg Standard Deviation 0	0.25 L/h/kg Standard Deviation 0.01	0.28 L/h/kg Standard Deviation 0.12	0.27 L/h/kg Standard Deviation 0	0.26 L/h/kg Standard Deviation 0.04	0.15 L/h/kg Standard Deviation 0	0.13 L/h/kg Standard Deviation 0.09	0.12 L/h/kg Standard Deviation 0

Deaths: 0 deaths

PU-H71, 470 mg/m^2

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PU-H71, 10 mg/m^2 n=1 participants at risk PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Cardiac disorders Atrioventricular block first degree	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Infections and infestations Lung Infection	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Nausea	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Cardiac disorders Sinus bradycardia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Vomiting	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.

Other adverse events

Other adverse events
Measure	PU-H71, 10 mg/m^2 n=1 participants at risk PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 20 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 40 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 60 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 80 mg/m^2 n=2 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 110 mg/m^2 n=3 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 150 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 200 mg/m^2 n=2 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 266 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 354 mg/m^2 n=3 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days	PU-H71, 470 mg/m^2 n=1 participants at risk PU-H71 will be administered IV over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Eye disorders Eye pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
General disorders Fatigue	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
General disorders Fever	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Diarrhea	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 4 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 3/3 • Number of events 5 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Nervous system disorders Dizziness	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Eye disorders Dry eye	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Abdominal pain - cramping	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Abdominal pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Alanine aminotransferase increased	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Alkaline phosphatase increased	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Blood and lymphatic system disorders Anemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Anorexia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Psychiatric disorders Anxiety	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Aspartate aminotransferase increased	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 2/2 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Bloating	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Blood bilirubin increased	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Eye disorders Blurred vision	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
General disorders Chills	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Psychiatric disorders Confusion	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Constipation	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations CPK increased	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Creatinine increased	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Dehydration	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Musculoskeletal and connective tissue disorders Flank pain - Left	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Vascular disorders Flushing	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Nervous system disorders Headache	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Renal and urinary disorders Hematuria	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Renal and urinary disorders Hemoglobinuria	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Hemorrhoids	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypercalcemia	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Vascular disorders Hypertension	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 7 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 2/2 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 3/3 • Number of events 8 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 4 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 2/2 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 3/3 • Number of events 4 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 4 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hyponatremia	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Endocrine disorders Hypothyroidism	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Infections and infestations Infection, device related	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Psychiatric disorders Insomnia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Lymphocyte count decreased	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 2/2 • Number of events 4 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
General disorders Malaise	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Mucositis oral	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Nausea	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Eye disorders Night blindness: intermittent	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Oral hemorrhage	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Oral pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Musculoskeletal and connective tissue disorders Pain in extremity- Right Ankle	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Nervous system disorders Paresthesia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Reproductive system and breast disorders Pelvic pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Cardiac disorders Pericardial effusion	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Vascular disorders Peripheral ischemia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations Platelet count decreased	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Rectal pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Cardiac disorders Sinus bradycardia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Cardiac disorders Sinus tachycardia	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	66.7% 2/3 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Infections and infestations Sinusitis	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Stomach pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Toothache	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Renal and urinary disorders Urinary frequency	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Infections and infestations Urinary tract infection	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Vascular disorders Peripheral vascular dis.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Gastrointestinal disorders Vomiting	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	50.0% 1/2 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 4 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	100.0% 1/1 • Number of events 1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.
Investigations White blood cell decreased	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	33.3% 1/3 • Number of events 2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/2 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/3 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.	0.00% 0/1 • 3 years and two months and 11 days Adverse events were collected and analyzed by dose level.

Additional Information

Dr. Shivaani Kummar

Stanford University School of Medicine

Phone: 650-724-9084

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place