Trial Outcomes & Findings for Nivolumab Plus Standard Dose Bevacizumab Versus Nivolumab Plus Low Dose Bevacizumab in GBM (NCT NCT03452579)

Last Updated: 2025-02-28

Results Overview

OS-12 is the percentage of participants in the analysis population who remain alive for at least twelve months following initiation of study therapy. Participants without efficacy evaluation data or without survival data will be censored at Day 1

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Up to 12 months after beginning therapy

Results posted on

2025-02-28

Participant Flow

Participant milestones

Participant milestones
Measure	Nivolumab + Standard Dose Bevacizumab nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Overall Study STARTED	45	45
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	42	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab + Standard Dose Bevacizumab nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Overall Study Death	0	1
Overall Study Withdrawal by Subject	2	0
Overall Study Disease progression, relapse during active treatment	38	37
Overall Study Physician Decision	1	1
Overall Study Adverse Event	1	4

Baseline Characteristics

Nivolumab Plus Standard Dose Bevacizumab Versus Nivolumab Plus Low Dose Bevacizumab in GBM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg	Total n=90 Participants Total of all reporting groups
Age, Continuous	60.7 Years n=99 Participants	60.5 Years n=107 Participants	60.6 Years n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	16 Participants n=107 Participants	29 Participants n=206 Participants
Sex: Female, Male Male	32 Participants n=99 Participants	29 Participants n=107 Participants	61 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=99 Participants	43 Participants n=107 Participants	86 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	2 Participants n=107 Participants	4 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	1 Participants n=107 Participants	2 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	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) White	40 Participants n=99 Participants	42 Participants n=107 Participants	82 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	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Region of Enrollment United States	45 participants n=99 Participants	45 participants n=107 Participants	90 participants n=206 Participants
Baseline Karnofsky Performance Scale (KPS) 70%	11 Participants n=99 Participants	13 Participants n=107 Participants	24 Participants n=206 Participants
Baseline Karnofsky Performance Scale (KPS) 80%	18 Participants n=99 Participants	17 Participants n=107 Participants	35 Participants n=206 Participants
Baseline Karnofsky Performance Scale (KPS) 90%	15 Participants n=99 Participants	13 Participants n=107 Participants	28 Participants n=206 Participants
Baseline Karnofsky Performance Scale (KPS) 100%	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Baseline Karnofsky Performance Scale (KPS) Unknown	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 12 months after beginning therapy

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Overall Survival at 12 Months (OS-12)	41.1 Percentage of participants Interval 26.1 to 56.1	37.7 Percentage of participants Interval 23.1 to 52.4

SECONDARY outcome

Timeframe: Up to six months after beginning treatment

The percentage of participants in the analysis population who remain progression-free for at least six months following initiation of study therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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 Participants without efficacy evaluation data or without survival data will be censored at Day 1

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Progression-Free Survival (PFS) at Six Months	46.7 Percentage of participants Interval 32.1 to 61.2	44.6 Percentage of participants Interval 29.4 to 59.8

SECONDARY outcome

Timeframe: Up to six months after beginning treatment

OS, as defined as number of participants alive from beginning of treatment up to 6 six months Participants without efficacy evaluation data or without survival data will be censored at Day 1

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Overall Survival (OS)	75.1 Percentage of participants Interval 62.3 to 87.9	57.4 Percentage of participants Interval 42.9 to 71.9

SECONDARY outcome

Timeframe: Up to 18 months after beginning treatment

OS, as defined as the percentage of participants alive from beginning of treatment up to 18 months. Participants without efficacy evaluation data or without survival data will be censored at Day 1

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Overall Survival (OS)	30.9 Percentage of participants Interval 15.7 to 46.1	22.5 Percentage of participants Interval 8.5 to 36.5

SECONDARY outcome

Timeframe: Up to 3 years after beginning treatment

Proportion of participants in the analysis population who have complete response (CR) or partial response (PR) using Radiologic Assessment in Neuro-Oncology criteria (RANO) criteria. Participants without efficacy evalaluation data or survival data censored at day 1. Participants without measurable disease will not be included.

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Overall Response Rate (ORR)	18 percentage of participants	16 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 years after beginning treatment

Median time from allocation to first documented disease progression per RANO or death due to any cause, whichever occurs first. Those without efficacy eval. data or survival data censored at day 1 RANO - progressive disease: * (\>) 25% increase in sum of products of perpendicular diameters of measurable lesions (over best response \[smallest tumor size\] or baseline if no decrease) on stable/increasing corticosteroid doses * Any new measurable lesion that when added to change in initial tumor(s) exceeds 25% increase in x-sectional area. * Clear clinical deterioration not attributable to causes apart from tumor. Def. is left to discretion of PI but recommended is: Decline in KPS from 100 or 90 to \<= 70, decline in KPS of at least 20 from \<= 80, or decline in KPS from any baseline to \<= 50, for \>= 7 days, be considered neurologic deterioration, unless attributable to co-morbid events or changes in corticosteroid dose. * Failure to return for eval. due to death or deteriorating condition

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Progression-Free Survival	4.1 months Interval 3.2 to 7.0	5.6 months Interval 3.7 to 6.8

SECONDARY outcome

Timeframe: Up to 3 years after beginning treatment

Time from first RANO response to disease progression in participants who achieve a PR or better Participants without efficacy evaluation data or without survival data will be censored at Day 1

Outcome measures

Outcome measures
Measure	Nivolumab + Standard Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 Participants nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Duration of Response	5.2 months Interval 3.5 to 6.6	5.2 months Interval 3.4 to 6.8

Adverse Events

Nivolumab + Standard Dose Bevacizumab

Serious events: 25 serious events

Other events: 45 other events

Deaths: 37 deaths

Nivolumab + Low Dose Bevacizumab

Serious events: 21 serious events

Other events: 44 other events

Deaths: 40 deaths

Serious adverse events

Other adverse events

Additional Information

David Peereboom, MD

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Phone: 1-866-223-8100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Nivolumab + Standard Dose Bevacizumab n=45 participants at risk nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 participants at risk nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Blood and lymphatic system disorders ALT Increase	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Blood and lymphatic system disorders Neutrophil decreased	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Cardiac disorders Deep vein thrombosis	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years
Cardiac disorders Hypertension	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years
Cardiac disorders Pulmonary Embolism	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Fatigue	13.3% 6/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Infection	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Pain	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Diarrhea	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Liver Function Abnormal	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Abnormal Electrolytes	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Immune System Other Cerebrit	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Lipase Increase	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Serum Amylase Increased	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Musculoskeletal and connective tissue disorders Gait Imbalance	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Headaches	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Intracranial Hemorrhage	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Other Neurologic	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years	11.1% 5/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Seizure	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years
Renal and urinary disorders Chronic Kidney Disease	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Respiratory, thoracic and mediastinal disorders Upper Resipratory Infection	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Skin and subcutaneous tissue disorders Rash	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years
Skin and subcutaneous tissue disorders Skin Ulceration	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Renal and urinary disorders CPK Increased	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Cognitive	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Aphasia	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Hyperglycemia	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Abnormal LFT	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Dehydration	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Lethargy	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years	0.00% 0/45 • Adverse events were collected while participants were on study up to 3 years

Measure	Nivolumab + Standard Dose Bevacizumab n=45 participants at risk nivolumab 240 mg IV and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Standard Dose Bevacizumab: 10mg/kg	Nivolumab + Low Dose Bevacizumab n=45 participants at risk nivolumab 240 mg IV and low dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity Nivolumab is to be administered first. The second infusion will be bevacizumab, and will start no sooner than 10 minutes after completion of the nivolumab infusion Nivolumab: 240mg Low Dose Bevacizumab: 3mg/kg
Blood and lymphatic system disorders ALT increased	24.4% 11/45 • Adverse events were collected while participants were on study up to 3 years	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years
Blood and lymphatic system disorders Bleed	28.9% 13/45 • Adverse events were collected while participants were on study up to 3 years	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years
Blood and lymphatic system disorders Platelet count decreased	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years	20.0% 9/45 • Adverse events were collected while participants were on study up to 3 years
Cardiac disorders Hypertension	33.3% 15/45 • Adverse events were collected while participants were on study up to 3 years	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Fatigue	64.4% 29/45 • Adverse events were collected while participants were on study up to 3 years	42.2% 19/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Diarrhea	37.8% 17/45 • Adverse events were collected while participants were on study up to 3 years	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Nausea	22.2% 10/45 • Adverse events were collected while participants were on study up to 3 years	24.4% 11/45 • Adverse events were collected while participants were on study up to 3 years
Investigations AST increased	20.0% 9/45 • Adverse events were collected while participants were on study up to 3 years	11.1% 5/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Hypothroidism	11.1% 5/45 • Adverse events were collected while participants were on study up to 3 years	13.3% 6/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Lipase Increased	31.1% 14/45 • Adverse events were collected while participants were on study up to 3 years	13.3% 6/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Serum amylase increased	20.0% 9/45 • Adverse events were collected while participants were on study up to 3 years	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years
Musculoskeletal and connective tissue disorders Body pain/stiffness	28.9% 13/45 • Adverse events were collected while participants were on study up to 3 years	24.4% 11/45 • Adverse events were collected while participants were on study up to 3 years
Musculoskeletal and connective tissue disorders Joint Pain	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Headache	44.4% 20/45 • Adverse events were collected while participants were on study up to 3 years	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Other-neurologic	28.9% 13/45 • Adverse events were collected while participants were on study up to 3 years	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years
Renal and urinary disorders Proteinuria	33.3% 15/45 • Adverse events were collected while participants were on study up to 3 years	37.8% 17/45 • Adverse events were collected while participants were on study up to 3 years
Respiratory, thoracic and mediastinal disorders Hiccups/hoarseness	11.1% 5/45 • Adverse events were collected while participants were on study up to 3 years	11.1% 5/45 • Adverse events were collected while participants were on study up to 3 years
Skin and subcutaneous tissue disorders Pruritus	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years
Skin and subcutaneous tissue disorders Rash	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Seizure	31.1% 14/45 • Adverse events were collected while participants were on study up to 3 years	28.9% 13/45 • Adverse events were collected while participants were on study up to 3 years
Nervous system disorders Behavioral Side effect	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years	22.2% 10/45 • Adverse events were collected while participants were on study up to 3 years
Cardiac disorders Chest Pain	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years	2.2% 1/45 • Adverse events were collected while participants were on study up to 3 years
Eye disorders Eye Discomfort	6.7% 3/45 • Adverse events were collected while participants were on study up to 3 years	11.1% 5/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Cough	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years	22.2% 10/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Flu Symptoms	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years	28.9% 13/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Infection	20.0% 9/45 • Adverse events were collected while participants were on study up to 3 years	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Insomnia	13.3% 6/45 • Adverse events were collected while participants were on study up to 3 years	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years
General disorders Weight loss	13.3% 6/45 • Adverse events were collected while participants were on study up to 3 years	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Abdominal Discomfort	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years	4.4% 2/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Constipation	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years	20.0% 9/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Dysphagia	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years	13.3% 6/45 • Adverse events were collected while participants were on study up to 3 years
Gastrointestinal disorders Vomiting	8.9% 4/45 • Adverse events were collected while participants were on study up to 3 years	15.6% 7/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Abnormal Electrocytes	40.0% 18/45 • Adverse events were collected while participants were on study up to 3 years	33.3% 15/45 • Adverse events were collected while participants were on study up to 3 years
Investigations Hyperglycemia	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years	17.8% 8/45 • Adverse events were collected while participants were on study up to 3 years
Investigations General Muscle Weakness	26.7% 12/45 • Adverse events were collected while participants were on study up to 3 years	31.1% 14/45 • Adverse events were collected while participants were on study up to 3 years