Trial Outcomes & Findings for Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma (NCT NCT03727841)

Last Updated: 2022-07-27

Results Overview

Progression was assessed by the Response assessment in neuro-oncology criteria (RANO) and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

6 months

Results posted on

2022-07-27

Participant Flow

There were plans to enroll participants in the pregnancy arm, however, participants were unable to be reached, thus no participants were enrolled on this arm, and no data was collected.

Participant milestones

Participant milestones
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Overall Study STARTED	3	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Overall Study Physician Decision	3	1

Baseline Characteristics

Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous	47.4 years STANDARD_DEVIATION 13.8 • n=99 Participants	32.3 years STANDARD_DEVIATION 0 • n=107 Participants	43.63 years STANDARD_DEVIATION 13.56 • n=206 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	3 participants n=99 Participants	1 participants n=107 Participants	4 participants n=206 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Number of Participants That Are Progression-free at 6 Months Time Point After Initiation of Treatment	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At end of study, up to 16 months

To determine the safety of marizomib in recurrent ependymoma patients and in a subset of patients with more than 2 prior chemotherapies (RELA-fusion Cohort 2 and non-RELA-fusion Cohort 4).

Outcome measures

Outcome measures
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Number of Toxicities by Grade Using the Common CTCAE Version 5.0. Grade 1	35 Toxicities	13 Toxicities
Number of Toxicities by Grade Using the Common CTCAE Version 5.0. Grade 2	24 Toxicities	5 Toxicities
Number of Toxicities by Grade Using the Common CTCAE Version 5.0. Grade 3	6 Toxicities	0 Toxicities
Number of Toxicities by Grade Using the Common CTCAE Version 5.0. Grade 4	0 Toxicities	0 Toxicities
Number of Toxicities by Grade Using the Common CTCAE Version 5.0. Grade 5	0 Toxicities	0 Toxicities

SECONDARY outcome

Timeframe: 6 months

Population: The one participant in Cohort 2 had progressive disease prior to 6 month mark and we did not enroll in Cohort 4 due to early study termination.

To estimate the efficacy of marizomib in recurrent ependymoma patients (RELA- fusion Cohort 2 and non RELA-fusion Cohort 4) with more than 2 prior chemotherapies as measured by progression free disease after 6 months. Progression was assessed by the Response Assessment in Neuro-oncology (RANO) criteria and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Outcome measures

Outcome measures
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Number of Participants That Have Progressive Disease After 6 Months	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Progression was assessed by the Response Assessment in Neuro-oncology criteria (RANO) and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Outcome measures

Outcome measures
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Number of Participants With 12-month Progression-free Survival (PFS12)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: End of study

Population: This outcome measure was not done because we were unable to determine due to low accrual and few data timepoints for which meaningful data could be extracted.

Changes in quality of life using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) instrument was used to determine symptom severity.To longitudinally evaluate participant reported outcome measures using self-reported symptom severity with daily activities using the MDASI-BT and/or MDASI-SP instrument.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 16 months

Population: We did not enroll to Cohort 4 due to early termination of the study.

To estimate the efficacy of marizomib in recurrent ependymoma patients (RELA- fusion Cohort 2 and non RELA-fusion Cohort 4) with more than 2 prior chemotherapies as measured by objective response. Complete Response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial Response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.

Outcome measures

Outcome measures
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Number of Participants Assessed Using the Response Assessment in Neuro-oncology Criteria (RANO) for Complete Response (CR) + Partial Response (PR)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months after therapy

Population: This outcome measure was not done. We were unable to determine as participants were taken off study for early study termination prior to the 12 months post therapy timepoint.

Median amount of time subject survives 12 months after therapy

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of treatment until end of study

Population: This outcome measure was not done. We were unable to determine for non RELA-fusion recurrent ependymoma patients since we did not enroll in those cohorts due to early study termination. And for the 4 participants with RELA-fusion recurrent ependymoma enrolled, the study was prematurely terminated pharmaceutical sponsor.

OS is defined as the time from treatment start date until date of death or date last known alive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of study

Population: This outcome measure was not done because we were unable to determine due to low accrual and few data timepoints for which meaningful data could be extracted.

Changes in quality of life using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) instrument was used to determine symptom interference.To longitudinally evaluate participant reported outcome measures using self-reported symptom interference with daily activities using the MDASI-BT and/or MDASI-SP instrument.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.

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	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 Participants Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 Participants Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	3 Participants	1 Participants

Adverse Events

1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 participants at risk Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 participants at risk Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.

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	1/Cohort 1 - Participants With Ependymoma Who Had None, One or Two Prior Chemotherapies n=3 participants at risk Marizomib at days 1, 8, and 15 of each 28-day cycle Marizomib: 0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. Participants with Intra-cranial or Spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)-fusion Ependymoma who have had none, 1 or 2 prior chemotherapies.	2/Cohort 2 - Participants With Ependymoma Who Had More Than Two Prior Chemotherapies n=1 participants at risk Participants with intra-cranial or spinal RELA-fusion ependymoma who had more than two prior chemotherapies.
Psychiatric disorders Agitation	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Ataxia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations Blood lactate dehydrogenase increased	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Psychiatric disorders Confusion	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations Creatinine increased	66.7% 2/3 • Number of events 5 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Psychiatric disorders Delirium	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Dysarthria	33.3% 1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Dysphasia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
General disorders Fatigue	66.7% 2/3 • Number of events 4 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
General disorders Flu like symptoms	0.00% 0/3 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations GGT increased	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
General disorders Gait disturbance	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Psychiatric disorders Hallucinations	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Headache	66.7% 2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Respiratory, thoracic and mediastinal disorders Hiccups	66.7% 2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Metabolism and nutrition disorders Hyperglycemia	66.7% 2/3 • Number of events 7 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Metabolism and nutrition disorders Hyperphosphatemia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Vascular disorders Hypertension	66.7% 2/3 • Number of events 7 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations Lymphocyte count decreased	33.3% 1/3 • Number of events 5 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 9 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Nervous system disorders - Other, Aphasia (word-finding difficulties)	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations Neutrophil count decreased	33.3% 1/3 • Number of events 5 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 5 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Nervous system disorders Paresthesia	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations Platelet count decreased	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Respiratory, thoracic and mediastinal disorders Productive cough	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations Serum amylase increased	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Renal and urinary disorders Urinary retention	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Infections and infestations Vaginal infection	0.00% 0/3 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Ear and labyrinth disorders Vestibular disorder	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Gastrointestinal disorders Vomiting	100.0% 3/3 • Number of events 6 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.
Investigations White blood cell decreased	33.3% 1/3 • Number of events 5 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.	100.0% 1/1 • Number of events 5 • Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.