Trial Outcomes & Findings for A Subject Treatment Preference Study of Tivozanib Versus Sunitinib in Subjects With Metastatic RCC (NCT NCT01673386)

Last Updated: 2020-10-27

Results Overview

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Up to 25 weeks

Results posted on

2020-10-27

Participant Flow

All screening assessments were performed within 28 days prior to the first dose of study drug. All subjects were recruited as per the inclusion and exclusion criteria.

Participant milestones

Participant milestones
Measure	Tivozanib First, Then Sunitinib Subject randomized to this arm received 1.5 mg oral tivozanib hydrochloride (drug 1) daily on a 3 weeks on/1 week off schedule for 12 weeks, followed by 50 mg oral sunitinib (drug 2) daily on a 4 weeks on/2 weeks off schedule for 12 weeks.	Sunitinib First, Then Tivosanib Subject randomized to this arm received 50 mg oral sunitinib (drug 1) daily on a 4 weeks on/2 weeks off schedule for 12 weeks, followed by 1.5 mg oral tivozanib hydrochloride (drug 2) daily on a 3 weeks on/1 week off schedule for 12 weeks.
Overall Study STARTED	27	31
Overall Study COMPLETED	2	4
Overall Study NOT COMPLETED	25	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Tivozanib First, Then Sunitinib Subject randomized to this arm received 1.5 mg oral tivozanib hydrochloride (drug 1) daily on a 3 weeks on/1 week off schedule for 12 weeks, followed by 50 mg oral sunitinib (drug 2) daily on a 4 weeks on/2 weeks off schedule for 12 weeks.	Sunitinib First, Then Tivosanib Subject randomized to this arm received 50 mg oral sunitinib (drug 1) daily on a 4 weeks on/2 weeks off schedule for 12 weeks, followed by 1.5 mg oral tivozanib hydrochloride (drug 2) daily on a 3 weeks on/1 week off schedule for 12 weeks.
Overall Study Study terminated by sponsor	16	22
Overall Study Adverse Event	5	2
Overall Study Progressive disease	4	1
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

A Subject Treatment Preference Study of Tivozanib Versus Sunitinib in Subjects With Metastatic RCC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=58 Participants Subjects randomized to Arm 1, received 1.5 mg oral tivozanib daily on a 3 week on/1 week off schedule for 12 weeks (3 cycles) followed by 50 mg oral sunitinib daily on a 4 week on/2 week off schedule for 12 weeks (2 cycles). Subjects randomized to Arm 2, received 50 mg oral sunitinib daily on a 4 week on/2 weeks off schedule for 12 weeks followed by 1.5 mg oral tivozanib daily on a 3 week on/1 week off schedule.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants
Age, Categorical >=65 years	32 Participants n=5 Participants
Age, Continuous	65.5 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: Descriptive statistical analyses were performed for a limited set of data (disposition, demographics, and adverse events).

Number of subjects with serious and non-serious adverse events.

Outcome measures

Outcome measures
Measure	Tivozanib n=38 Participants Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib n=41 Participants Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Number of Subjects With AEs and SAEs At least one AE	35 Participants	40 Participants
Number of Subjects With AEs and SAEs At least one treatment-related AE	33 Participants	38 Participants
Number of Subjects With AEs and SAEs At least one serious AE (SAE)	6 Participants	7 Participants
Number of Subjects With AEs and SAEs At least one treatment-related SAE	1 Participants	3 Participants
Number of Subjects With AEs and SAEs At least one AE leading to drug withdrawal	3 Participants	8 Participants
Number of Subjects With AEs and SAEs At least one AE with outcome of death	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Population: The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Tivozanib

Serious events: 6 serious events

Other events: 35 other events

Deaths: 0 deaths

Sunitinib

Serious events: 7 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

AVEO Pharmaceuticals, Inc.

Phone: 857-400-0101

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Tivozanib n=38 participants at risk Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib n=41 participants at risk Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Gastrointestinal disorders Nausea	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Vomiting	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Oesophagitis	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Fatigue	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Pyrexia	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Asthenia	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Blood and lymphatic system disorders Anaemia	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Nervous system disorders Headache	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Vascular disorders Hypotension	0.00% 0/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Hepatobiliary disorders Hyperbilirubinaemia	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Infections and infestations Subcutaneous abscess	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Metabolism and nutrition disorders Decreased appetite	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Musculoskeletal and connective tissue disorders Flank pain	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.

Other adverse events
Measure	Tivozanib n=38 participants at risk Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib n=41 participants at risk Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Gastrointestinal disorders Diarrhoea	44.7% 17/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	36.6% 15/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Stomatitis	21.1% 8/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	22.0% 9/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Constipation	13.2% 5/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	7.3% 3/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Gingival pain	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Nausea	13.2% 5/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	34.1% 14/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Vomiting	7.9% 3/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	19.5% 8/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Abdominal pain upper	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	12.2% 5/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Dry mouth	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Dyspepsia	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	24.4% 10/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Flatulence	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	12.2% 5/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Gastrointestinal disorders Oral pain	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Dysphonia	36.8% 14/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	12.2% 5/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.2% 5/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	17.1% 7/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Cough	15.8% 6/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	9.8% 4/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Blood and lymphatic system disorders Anaemia	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	9.8% 4/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Renal and urinary disorders Proteinuria	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	7.3% 3/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Renal and urinary disorders Haematuria	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Psychiatric disorders Insomnia	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Metabolism and nutrition disorders Decreased appetite	18.4% 7/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	26.8% 11/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Metabolism and nutrition disorders Dehydration	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Metabolism and nutrition disorders Hyponatraemia	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Investigations Weight decreased	10.5% 4/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Investigations Blood creatinine increased	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	7.3% 3/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Infections and infestations Nasopharyngitis	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Infections and infestations Tooth infection	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	2.4% 1/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Infections and infestations Upper respiratory tract infection	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Infections and infestations Urinary tract infection	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Fatigue	36.8% 14/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	43.9% 18/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Asthenia	18.4% 7/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	22.0% 9/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Oedema peripheral	7.9% 3/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	12.2% 5/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
General disorders Pyrexia	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	12.2% 5/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Vascular disorders Hypertension	50.0% 19/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	29.3% 12/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Vascular disorders Hypotension	7.9% 3/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	9.8% 4/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	18.4% 7/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	24.4% 10/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Skin and subcutaneous tissue disorders Pruritus	7.9% 3/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Skin and subcutaneous tissue disorders Rash	7.9% 3/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	9.8% 4/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Skin and subcutaneous tissue disorders Hair colour changes	2.6% 1/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	14.6% 6/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Musculoskeletal and connective tissue disorders Pain in extremity	7.9% 3/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	4.9% 2/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 2/38 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.	0.00% 0/41 • Collected from the time of signing the Informed Consent Form until 30 days after permanent treatment discontinuation at Week 25 (2 sequential 12-week treatment periods with a 1-week washout period). The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA. Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.