Trial Outcomes & Findings for Sunitinib in Sarcomas of the Central Nervous System (NCT NCT03641326)

Last Updated: 2022-04-19

Results Overview

Objective Response is defined as all participants who had greater than 50% reduction in Complete Response and Partial Response assessed by the Assessment in Neuro-oncology Criteria (RANO criteria). Complete Response is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) or clinical status. Partial Response is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

From enrollment to off study, approximately 3 Months, 1 Week, 4 Days

Results posted on

2022-04-19

Participant Flow

No participants with Primary Central Nervous System (CNS) Sarcoma were enrolled in Cohort 3.

Participant milestones

Participant milestones
Measure	Participants With Primary Gliosarcoma Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.
Overall Study STARTED	2	3
Overall Study COMPLETED	2	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sunitinib in Sarcomas of the Central Nervous System

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants With Primary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	67.7 years STANDARD_DEVIATION 12.45 • n=5 Participants	58.6 years STANDARD_DEVIATION 10.16 • n=7 Participants	62.24 years STANDARD_DEVIATION 10.73 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: From enrollment to off study, approximately 3 Months, 1 Week, 4 Days

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Number of Participants With Greater Than 50% Reduction in Objective Response Complete Response	0 Participants	0 Participants	—	—
Number of Participants With Greater Than 50% Reduction in Objective Response Partial Response	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 6 months

Progression is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. PFS was assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). Progression is ≥25% increase in T1 gadolinium enhancing disease, increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR), presence of new lesions, and decrease in clinical status.

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Number of Participants With 6-month Progression Free Survival (PFS)	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: After 18 months

Population: This outcome measure was not analyzed because none of the participants reached 6 months progression free survival (PFS), thus we could not assess participants for 18 months PFS.

Progressive disease was assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). Progression is ≥25% increase in T1 gadolinium enhancing disease, increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR), presence of new lesions, and decrease in clinical status.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to off study, approximately 3 months and 12 days

Adverse events was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Number of Adverse Events Related to Drug	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: end of study, approximately 25 months and 12 days.

Population: Analysis not done. There were not enough samples collected to provide results.

To evaluate archival tumor tissue for activation of signaling pathways targeted by sunitinib to establish potential biomarkers of response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline to end of treatment, approximately 25 months and 12 days.

Population: 0 participants achieved a response in the responders with primary gliosarcoma group and responders with secondary gliosarcoma group.

Molecular profiling of archival tumor tissues was used to identify tumor markers of activation of response to sunitinib in responders and non-responders. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma n=3 Participants A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Number of Responders and Non-responders With Tumor Markers of Activation	0 Participants	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Pre-treatment and post treatment, approximately 25 months and 12 days.

Population: This outcome measure was not done because no data was collected because the perfusion blood volume was not measured.

Perfusion was quantitated in responders and non-responders comparing pre and post treatment to determine if the treatment regimen altered vasculature and blood flow to the tumor. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \<25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Before (baseline) and during treatment with Sunitinib every 6 weeks, up to approximately 25 months and 12 days.

Population: 0 participants achieved a response in the responders with primary gliosarcoma group and responders with secondary gliosarcoma group.

Dynamic contrast enhanced magnetic resonance imaging (MRI) was performed before and during treatment with sunitinib in responders and non-responders. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma n=3 Participants A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Number of Responders and Non-responders With Dynamic Contrast Enhanced Magnetic Resonance Imaging (MRI) Performed Before and During Treatment With Sunitinib. Baseline	0 Participants	2 Participants	0 Participants	3 Participants
Number of Responders and Non-responders With Dynamic Contrast Enhanced Magnetic Resonance Imaging (MRI) Performed Before and During Treatment With Sunitinib. During Treatment	0 Participants	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and off treatment, approximately 25 months and 12 days

Population: 2 participants only had baseline MDASI, \& 1 participant had baseline\&off treatment MDASI in the secondary glioblastoma group. The number of participants enrolled =5 \& analyses were performed on a subset of collected data. No conclusions should be drawn from the reported data on whether participants had a change in quality of life. Only treatment toxicity evaluation is meaningful \& this will not vary by the histologic subtype of the tumor. Thus, combining the 2 groups is most logical \& expedient.

Participants reported outcome measures using a self-reported symptom severity and interference with daily activities using the MDASI-BT. The MDASI-BT consists of symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. All patients with at least one valid questionnaire will be included in the analyses. This outcome measure was predicated on change. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity and symptom interference measures.

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Mean Symptom Severity and Interference From Baseline Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Baseline mean symptom severity	2.4 Score on a scale Standard Deviation 1.5	—	—	—
Mean Symptom Severity and Interference From Baseline Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Baseline mean symptom interference	3.4 Score on a scale Standard Deviation 3.4	—	—	—
Mean Symptom Severity and Interference From Baseline Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Mean symptom severity at disease progression	0.4 Score on a scale Standard Deviation NA Standard Deviation cannot be calculated at disease progression due to n=1.	—	—	—
Mean Symptom Severity and Interference From Baseline Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Mean symptom interference at disease progression	0.2 Score on a scale Standard Deviation NA Standard Deviation cannot be calculated at disease progression due to n=1.	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to off study, approximately 3 months and 12 days

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Participants With Primary Gliosarcoma n=2 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 Participants Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Responders With Secondary Gliosarcoma A responder is a participant with a Complete Response (CR) or Partial Response (PR).	Non-Responders With Secondary Gliosarcoma A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	2 Participants	3 Participants	—	—

Adverse Events

Participants With Primary Gliosarcoma

Serious events: 2 serious events

Other events: 2 other events

Deaths: 2 deaths

Participants With Secondary Gliosarcoma

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Participants With Primary Gliosarcoma n=2 participants at risk Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 participants at risk Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.
General disorders Edema face	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Injury, poisoning and procedural complications Fall	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
General disorders Fatigue	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days
General disorders Fever	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Headache	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	66.7% 2/3 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Hydrocephalus	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Nausea	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Gliosarcoma	100.0% 2/2 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Nervous system disorders - Other, Apraxia	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Somnolence	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Vomiting	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days

Other adverse events

Additional Information

Dr. Mark Gilbert

National Cancer Institute

Phone: 240-760-6023

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Participants With Primary Gliosarcoma n=2 participants at risk Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.	Participants With Secondary Gliosarcoma n=3 participants at risk Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.
Investigations Alanine aminotransferase increased	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days
Investigations Alkaline phosphatase increased	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Investigations Aspartate aminotransferase increased	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Constipation	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Investigations Creatinine increased	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Diarrhea	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Dysgeusia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Dyspepsia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Renal and urinary disorders Dysuria	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
General disorders Facial pain	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Injury, poisoning and procedural complications Fall	50.0% 1/2 • Number of events 3 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
General disorders Fatigue	100.0% 2/2 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
General disorders Gait disturbance	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days
General disorders General disorders and administration site conditions - Other, bilateral feet ache	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Headache	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	66.7% 2/3 • Number of events 4 • Baseline to off study, approximately 3 months and 12 days
Vascular disorders Hematoma	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Metabolism and nutrition disorders Hypermagnesemia	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Vascular disorders Hypertension	100.0% 2/2 • Number of events 8 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 3 • Baseline to off study, approximately 3 months and 12 days
Metabolism and nutrition disorders Hypokalemia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days
Metabolism and nutrition disorders Hyponatremia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Psychiatric disorders Insomnia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Investigations Lymphocyte count decreased	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	66.7% 2/3 • Number of events 6 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Memory impairment	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Musculoskeletal and connective tissue disorders Muscle cramp	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Nausea	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Nervous system disorders - Other, apraxia	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Investigations Neutrophil count decreased	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Paresthesia	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Investigations Platelet count decreased	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Nervous system disorders Seizure	50.0% 1/2 • Number of events 2 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Yellowing skin	50.0% 1/2 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days	0.00% 0/3 • Baseline to off study, approximately 3 months and 12 days
Gastrointestinal disorders Toothache	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days
Investigations White blood cell decreased	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	66.7% 2/3 • Number of events 3 • Baseline to off study, approximately 3 months and 12 days
Infections and infestations Wound infection	0.00% 0/2 • Baseline to off study, approximately 3 months and 12 days	33.3% 1/3 • Number of events 1 • Baseline to off study, approximately 3 months and 12 days