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

• Sponsor: AVEO Pharmaceuticals, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01673386
• Collaborator: Astellas Pharma Inc (Industry)
• Enrollment: 58
• Locations: 38
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Randomized, double-blind, 2-arm crossover study comparing tivozanib hydrochloride and sunitinib in subjects with metastatic RCC who have received no prior systemic therapy for Renal Cell Carcinoma (RCC).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: Tivozanib; Drug: Sunitinib	Phase 2

Detailed Description

This is a randomized, double-blind, 2-arm crossover study comparing tivozanib hydrochloride and sunitinib in subjects with metastatic RCC who have received no prior systemic therapy for Renal Cell Carcinoma (RCC). Approximately 160 subjects will be stratified for ECOG score (0 vs 1) and histology (clear cell vs non-clear cell) and then will be randomized 1:1 to 1 of 2 treatment arms. The study consists of two 12-week treatment periods with a 1-week washout in between. Subjects will receive double-blind (over-encapsulated) tivozanib hydrochloride and sunitinib sequentially. The study is designed to compare subject treatment preference, as well as overall safety and tolerability, frequency of dose modifications and kidney-specific health outcomes/QoL.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Randomized, Double-Blind, Crossover, Controlled, Multi-Center Subject Preference Study of Tivozanib Hydrochloride Versus Sunitinib in the Treatment of Subjects With Metastatic Renal Cell Carcinoma
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tivozanib Hydrochloride 1.5 mg oral tivozanib hydrochloride daily on a 3 weeks on/1 week off schedule for 12 weeks, followed by 50 mg oral sunitinib daily on a 4 weeks on/2 weeks off schedule for 12 weeks.	Drug: Tivozanib; Other Names: Tivozanib Hydrochloride
Active Comparator: Sunitinib 50 mg oral sunitinib daily on a 4 weeks on/2 weeks off schedule for 12 weeks, followed by 1.5 mg oral tivozanib hydrochloride daily on a 3 weeks on/1 week off schedule for 12 weeks.	Drug: Sunitinib; Other Names: Sutent

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects Who Prefer Tivozanib Hydrochloride or Sunitinib [Up to 25 weeks]

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

Secondary Outcome Measures

1. Number of Subjects With AEs and SAEs [Up to 25 weeks]

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

2. Number of Subjects With Dose Reductions [Up to 25 weeks]

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

3. Number of Subjects With Dose Interruptions [Up to 25 weeks]

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

4. Number of Subjects With Grade 3/4 Hematology Abnormalities [Up to 25 weeks]

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

5. Number of Subjects With Grade 3/4 Chemistry Abnormalities [Up to 25 weeks]

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

6. Number of Subjects With Grade 3/4 Coagulation Abnormalities [Up to 25 weeks]

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

7. Number of Subjects With Grade 3/4 Urinalysis Abnormalities [Up to 25 weeks]

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

8. Number of Subjects With Grade 3/4 Thyroid Function Abnormalities [Up to 25 weeks]

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

9. Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) [Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment]

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

10. Change From Baseline in FACT Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) [Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment]

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

11. Change From Baseline in Functional Assessment of Cancer Therapy-Diarrhea (FACT-D) [Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment]

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

12. Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D) [Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Unresectable mRCC

• Histologically or cytologically confirmed RCC of any histology

• Subjects with or without prior nephrectomy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Any prior systemic therapy for treatment of mRCC (including investigational or licensed drugs that target VEGF or VEGF receptors/pathway, or are mammalian target of rapamycin [mTOR] inhibitors)

• Central nervous system malignancies or metastases

• Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders

• Significant serum chemistry or urinalysis abnormalities

• Significant cardiovascular disease, including symptomatic left ventricular ejection fraction or baseline LVEF of ≤ institutional lower limit of normal, uncontrolled hypertension, myocardial infarction or severe angina within 6 months prior to administration of first dose of study drug, history of class III or IV congestive heart failure, or history of serious ventricular arrhythmia, cardiac arrhythmias, or coronary or peripheral bypass graft within 6 months of screening

• Corrected QT interval (QTc) of >480 msec using Bazett's formula

• Currently active second primary malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States	90001
2		Albany	Georgia	United States	31701
3		Atlanta	Georgia	United States	30301
4		Chicago	Illinois	United States	60007
5		Indianapolis	Indiana	United States	46077
6		Shreveport	Louisiana	United States	71101
7		Worcester	Massachusetts	United States	01601
8		Minneapolis	Minnesota	United States	55111
9		New York	New York	United States	10001
10		Columbus	Ohio	United States	43004
11		Portland	Oregon	United States	97035
12		Charleston	South Carolina	United States	29401
13		Myrtle Beach	South Carolina	United States	29572
14		San Antonio	Texas	United States	78006
15		Madison	Wisconsin	United States	53558
16		Antwerp		Belgium
17		Brussels		Belgium
18		Bordeaux		France
19		Caen		France
20		Lyon		France
21		Paris		France
22		Berlin		Germany
23		Hamburg		Germany
24		Hannover		Germany
25		Heidelberg		Germany
26		Munich		Germany
27		Aviano		Italy
28		Pavia		Italy
29		Rome		Italy
30		Barcelona		Spain
31		Madrid		Spain
32		Pamplona		Spain
33		Valencia		Spain
34		Glasgow	Scotland	United Kingdom
35		Swansea	Wales	United Kingdom
36		Cambridge		United Kingdom
37		London		United Kingdom
38		Manchester		United Kingdom

Sponsors and Collaborators

• AVEO Pharmaceuticals, Inc.
• Astellas Pharma Inc

Investigators

• Study Chair: Michael Needle, MD, AVEO Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Aveo Pharmaceuticals, Inc. official web page

Publications

None provided.

• Responsible Party: AVEO Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01673386
• Other Study ID Numbers: AV-951-12-205
• First Posted: Aug 28, 2012
• Last Update Posted: Oct 27, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by AVEO Pharmaceuticals, Inc.: Tivozanib hydrochloride; renal cell carcinoma; subject preference; quality of life
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Tivozanib First, Then Sunitinib	Sunitinib First, Then Tivosanib
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	27	31
COMPLETED	2	4
NOT COMPLETED	25	27

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	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.
Overall Participants	58
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	26 44.8%
>=65 years	32 55.2%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.5
Sex: Female, Male (Count of Participants)
Female	10 17.2%
Male	48 82.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1.7%
White	56 96.6%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Who Prefer Tivozanib Hydrochloride or Sunitinib
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Subjects With AEs and SAEs
Description	Number of subjects with serious and non-serious adverse events.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	38	41
At least one AE	35 60.3%	40 NaN
At least one treatment-related AE	33 56.9%	38 NaN
At least one serious AE (SAE)	6 10.3%	7 NaN
At least one treatment-related SAE	1 1.7%	3 NaN
At least one AE leading to drug withdrawal	3 5.2%	8 NaN
At least one AE with outcome of death	2 3.4%	1 NaN

3. Secondary Outcome

Title	Number of Subjects With Dose Reductions
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Subjects With Dose Interruptions
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

5. Secondary Outcome

Title	Number of Subjects With Grade 3/4 Hematology Abnormalities
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Subjects With Grade 3/4 Chemistry Abnormalities
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

7. Secondary Outcome

Title	Number of Subjects With Grade 3/4 Coagulation Abnormalities
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

8. Secondary Outcome

Title	Number of Subjects With Grade 3/4 Urinalysis Abnormalities
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

9. Secondary Outcome

Title	Number of Subjects With Grade 3/4 Thyroid Function Abnormalities
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

11. Secondary Outcome

Title	Change From Baseline in FACT Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS)
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

12. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy-Diarrhea (FACT-D)
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

13. Secondary Outcome

Title	Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D)
Description	The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure.
Time Frame	Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Tivozanib	Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.	Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
Measure Participants	0	0

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	Serious treatment-emergent adverse events and treatment-emergent adverse events in Safety (SAF) Population was reported.
Arm/Group Title	Tivozanib		Sunitinib
Arm/Group Description	Tivozanib hydrochloride 1.5 mg was administered orally to the randomized subjects first in arm 1 and second in arm 2.		Sunitinib 50 mg was administered orally to the randomized subjects first in arm 2 and second in arm 1.
All Cause Mortality
	Tivozanib		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tivozanib		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/38 (15.8%)		7/41 (17.1%)
Blood and lymphatic system disorders
Anaemia	0/38 (0%)		1/41 (2.4%)
Thrombocytopenia	0/38 (0%)		1/41 (2.4%)
Gastrointestinal disorders
Nausea	0/38 (0%)		2/41 (4.9%)
Vomiting	0/38 (0%)		2/41 (4.9%)
Gastric ulcer haemorrhage	0/38 (0%)		1/41 (2.4%)
Rectal haemorrhage	0/38 (0%)		1/41 (2.4%)
Oesophagitis	1/38 (2.6%)		0/41 (0%)
General disorders
Fatigue	0/38 (0%)		1/41 (2.4%)
Pyrexia	0/38 (0%)		1/41 (2.4%)
Asthenia	2/38 (5.3%)		0/41 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/38 (2.6%)		0/41 (0%)
Infections and infestations
Subcutaneous abscess	1/38 (2.6%)		0/41 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/38 (2.6%)		0/41 (0%)
Musculoskeletal and connective tissue disorders
Flank pain	1/38 (2.6%)		0/41 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	0/38 (0%)		1/41 (2.4%)
Neoplasm progression	1/38 (2.6%)		0/41 (0%)
Nervous system disorders
Headache	0/38 (0%)		1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/38 (2.6%)		2/41 (4.9%)
Pulmonary embolism	1/38 (2.6%)		0/41 (0%)
Atelectasis	0/38 (0%)		1/41 (2.4%)
Pleural effusion	0/38 (0%)		1/41 (2.4%)
Respiratory failure	0/38 (0%)		1/41 (2.4%)
Vascular disorders
Hypotension	0/38 (0%)		1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Tivozanib		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/38 (92.1%)		40/41 (97.6%)
Blood and lymphatic system disorders
Anaemia	1/38 (2.6%)		4/41 (9.8%)
Thrombocytopenia	0/38 (0%)		6/41 (14.6%)
Neutropenia	0/38 (0%)		2/41 (4.9%)
Eye disorders
Eyelid oedema	0/38 (0%)		3/41 (7.3%)
Gastrointestinal disorders
Diarrhoea	17/38 (44.7%)		15/41 (36.6%)
Stomatitis	8/38 (21.1%)		9/41 (22%)
Constipation	5/38 (13.2%)		3/41 (7.3%)
Gingival pain	2/38 (5.3%)		0/41 (0%)
Nausea	5/38 (13.2%)		14/41 (34.1%)
Vomiting	3/38 (7.9%)		8/41 (19.5%)
Abdominal pain upper	2/38 (5.3%)		5/41 (12.2%)
Dry mouth	2/38 (5.3%)		2/41 (4.9%)
Dyspepsia	2/38 (5.3%)		10/41 (24.4%)
Flatulence	1/38 (2.6%)		5/41 (12.2%)
Oral pain	1/38 (2.6%)		2/41 (4.9%)
Abdominal pain	1/38 (2.6%)		3/41 (7.3%)
Rectal haemorrhage	0/38 (0%)		3/41 (7.3%)
Gastrooesophageal reflux disease	0/38 (0%)		2/41 (4.9%)
Oral dysaesthesia	0/38 (0%)		2/41 (4.9%)
General disorders
Fatigue	14/38 (36.8%)		18/41 (43.9%)
Asthenia	7/38 (18.4%)		9/41 (22%)
Oedema peripheral	3/38 (7.9%)		5/41 (12.2%)
Pyrexia	2/38 (5.3%)		5/41 (12.2%)
Chills	0/38 (0%)		3/41 (7.3%)
Hepatobiliary disorders
Jaundice	0/38 (0%)		4/41 (9.8%)
Infections and infestations
Nasopharyngitis	2/38 (5.3%)		0/41 (0%)
Tooth infection	2/38 (5.3%)		1/41 (2.4%)
Upper respiratory tract infection	2/38 (5.3%)		0/41 (0%)
Urinary tract infection	2/38 (5.3%)		2/41 (4.9%)
Injury, poisoning and procedural complications
Contusion	0/38 (0%)		2/41 (4.9%)
Investigations
Weight decreased	4/38 (10.5%)		0/41 (0%)
Blood creatinine increased	1/38 (2.6%)		3/41 (7.3%)
Lipase increased	0/38 (0%)		5/41 (12.2%)
Amylase increased	0/38 (0%)		3/41 (7.3%)
Platelet count decreased	0/38 (0%)		3/41 (7.3%)
White blood cell count decreased	0/38 (0%)		2/41 (4.9%)
Metabolism and nutrition disorders
Decreased appetite	7/38 (18.4%)		11/41 (26.8%)
Dehydration	2/38 (5.3%)		1/41 (2.4%)
Hyponatraemia	1/38 (2.6%)		2/41 (4.9%)
Musculoskeletal and connective tissue disorders
Pain in extremity	3/38 (7.9%)		2/41 (4.9%)
Arthralgia	2/38 (5.3%)		0/41 (0%)
Back pain	2/38 (5.3%)		6/41 (14.6%)
Musculoskeletal pain	2/38 (5.3%)		0/41 (0%)
Musculoskeletal stiffness	2/38 (5.3%)		0/41 (0%)
Muscle spasms	1/38 (2.6%)		2/41 (4.9%)
Myalgia	0/38 (0%)		4/41 (9.8%)
Nervous system disorders
Headache	5/38 (13.2%)		1/41 (2.4%)
Dysgeusia	4/38 (10.5%)		17/41 (41.5%)
Dizziness	3/38 (7.9%)		3/41 (7.3%)
Neuropathy peripheral	0/38 (0%)		2/41 (4.9%)
Paraesthesia	1/38 (2.6%)		2/41 (4.9%)
Psychiatric disorders
Insomnia	2/38 (5.3%)		1/41 (2.4%)
Renal and urinary disorders
Proteinuria	1/38 (2.6%)		3/41 (7.3%)
Haematuria	1/38 (2.6%)		2/41 (4.9%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	14/38 (36.8%)		5/41 (12.2%)
Dyspnoea	5/38 (13.2%)		7/41 (17.1%)
Cough	6/38 (15.8%)		4/41 (9.8%)
Oropharyngeal pain	2/38 (5.3%)		0/41 (0%)
Epistaxis	0/38 (0%)		6/41 (14.6%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	7/38 (18.4%)		10/41 (24.4%)
Pruritus	3/38 (7.9%)		2/41 (4.9%)
Rash	3/38 (7.9%)		4/41 (9.8%)
Hair colour changes	1/38 (2.6%)		6/41 (14.6%)
Yellow skin	0/38 (0%)		4/41 (9.8%)
Alopecia	1/38 (2.6%)		3/41 (7.3%)
Dry skin	0/38 (0%)		3/41 (7.3%)
Skin discolouration	0/38 (0%)		3/41 (7.3%)
Vascular disorders
Hypertension	19/38 (50%)		12/41 (29.3%)
Hypotension	3/38 (7.9%)		4/41 (9.8%)
Deep vein thrombosis	0/38 (0%)		2/41 (4.9%)

Limitations/Caveats

The Sponsor terminated Study AV-951-12-205 before enrollment was completed, following the negative decision of the US FDA.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.