Trial Outcomes & Findings for A Rollover Protocol to Allow Continued Access to Tivozanib (AV 951) for Subjects Enrolled in Other Tivozanib Protocols (NCT NCT01369433)
NCT ID: NCT01369433
Last Updated: 2020-09-01
Results Overview
Safety and tolerability will be assessed in accordance to the protocol of the parent study in which the subjects had participated, before enrolling in the AV-951-09-901 rollover study.
Recruitment status
TERMINATED
Study phase
NA
Target enrollment
225 participants
Primary outcome timeframe
24 Months
Results posted on
2020-09-01
Participant Flow
Subjects who met all the inclusion and none of the exclusion criteria were enrolled in the study.
All subjects underwent inclusion and exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures. All the study assessments were performed as per the schedule of assessment.
Participant milestones
| Measure |
Monotherapy
Subjects received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride.
|
Combination Therapy
Subjects who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible subjects who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine.
|
|---|---|---|
|
Overall Study
STARTED
|
209
|
16
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
209
|
16
|
Reasons for withdrawal
| Measure |
Monotherapy
Subjects received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride.
|
Combination Therapy
Subjects who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible subjects who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine.
|
|---|---|---|
|
Overall Study
Adverse Event
|
31
|
1
|
|
Overall Study
Required significant surgical procedure
|
1
|
0
|
|
Overall Study
Non-compliance
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
|
Overall Study
Study terminated by Sponsor
|
67
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Death
|
5
|
0
|
|
Overall Study
Investigator discretion
|
6
|
1
|
|
Overall Study
Progressive Disease
|
92
|
12
|
Baseline Characteristics
A Rollover Protocol to Allow Continued Access to Tivozanib (AV 951) for Subjects Enrolled in Other Tivozanib Protocols
Baseline characteristics by cohort
| Measure |
Monotherapy
n=209 Participants
Participants received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride.
|
Combination Therapy
n=16 Participants
Participants who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible participants who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine.
|
Total
n=225 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to >= 75 years
|
209 participants
n=5 Participants
|
16 participants
n=7 Participants
|
225 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
80 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
129 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
139 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
199 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
215 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 MonthsPopulation: Of the 225 subjects, 209 subjects had monotherapy treatment during their parent study; the remaining subjects (N=16) had combination therapy * Monotherapy: Studies AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, AV-951-09-902. * Combination: Studies AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, AV-951-12-204.
Safety and tolerability will be assessed in accordance to the protocol of the parent study in which the subjects had participated, before enrolling in the AV-951-09-901 rollover study.
Outcome measures
| Measure |
Monotherapy
n=209 Participants
Participants received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride.
|
Combination Therapy
n=16 Participants
Participants who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible participants who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine.
|
|---|---|---|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
AEs
|
178 Participants
|
16 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
Treatment-related AEs
|
159 Participants
|
15 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
AEs ≥Grade 3 toxicity
|
111 Participants
|
12 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
AEs-study drug interruption
|
54 Participants
|
6 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
AEs-study drug dose reduction
|
13 Participants
|
0 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
AEs-discontinuation of study drug
|
31 Participants
|
1 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
AEs-death
|
13 Participants
|
1 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
Serious Adverse events (SAEs)
|
44 Participants
|
5 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
SAEs ≥Grade 3 toxicity
|
38 Participants
|
5 Participants
|
|
Number of Subjects With Adverse Events (AEs) and Serious AEs
Serious treatment-related AEs
|
16 Participants
|
0 Participants
|
Adverse Events
Monotherapy
Serious events: 44 serious events
Other events: 178 other events
Deaths: 0 deaths
Combination Therapy
Serious events: 5 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Monotherapy
n=209 participants at risk
Participants received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride.
|
Combination Therapy
n=16 participants at risk
Participants who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible participants who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Cardiac disorders
Myocardial infarction
|
2.4%
5/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Cardiac disorders
Cardiac arrest
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Cardiac disorders
Cardiac failure acute
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Cardiac disorders
Cardiac failure congestive
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Endocrine disorders
Hypothyroidism
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Eye disorders
Cataract
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Constipation
|
1.4%
3/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.96%
2/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Nausea
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.96%
2/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Ascites
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Periproctitis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Vomiting
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
General disorders
Disease progression
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Fatigue
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
General disorders
Multi-organ failure
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
General disorders
Non-cardiac chest pain
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
General disorders
Pain
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Hepatobiliary disorders
Hepatic failure
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Infections and infestations
Pneumonia
|
1.4%
3/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Infections and infestations
Cystitis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Infections and infestations
Diverticulitis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Infections and infestations
Gastroenteritis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Infections and infestations
Sepsis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Dehydration
|
3.3%
7/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Hypochloraemia
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
0.96%
2/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Spinal cord compression
|
0.96%
2/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Balance disorder
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Convulsion
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Dysarthria
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Headache
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Nervous system disorders
Syncope
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Psychiatric disorders
Mental status changes
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Renal and urinary disorders
Hydronephrosis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Renal and urinary disorders
Renal failure acute
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.4%
5/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Vascular disorders
Orthostatic hypotension
|
0.48%
1/209 • 24 months
|
0.00%
0/16 • 24 months
|
Other adverse events
| Measure |
Monotherapy
n=209 participants at risk
Participants received oral tivozanib hydrochloride at the same dose and schedule as during the parent protocol. Studies under monotherapy were AV-951-10-112, AV-951-07-201, AV-951-110-202, AV-951-12-205, and AV-951-09-902. Drug: Tivozanib hydrochloride.
|
Combination Therapy
n=16 participants at risk
Participants who were receiving tivozanib hydrochloride combination, continued the combination therapy, as long as it was tolerated, at the same dose and schedule as in the parent protocol. Eligible participants who received sorafenib in Parent Study AV-951-09-902 at the time of study termination and who rolled into Study AV-951-09-901 began tivozanib hydrochloride at a dose of 1.5 mg/day. Studies under combination therapy were AV-951-07-102, AV-951-07-103, AV-951-08-104, AV-951-10-114, and AV-951-12-204. Combination Drugs: Tivozanib hydrochloride + temsirolimus, Tivozanib hydrochloride + paclitaxel, and Tivozanib hydrochloride + capecitabine.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.3%
11/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Endocrine disorders
Hypothyroidism
|
17.2%
36/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Gastrointestinal disorders
Diarrhoea
|
41.6%
87/209 • 24 months
|
50.0%
8/16 • 24 months
|
|
Gastrointestinal disorders
Nausea
|
25.4%
53/209 • 24 months
|
50.0%
8/16 • 24 months
|
|
Gastrointestinal disorders
Vomiting
|
13.4%
28/209 • 24 months
|
31.2%
5/16 • 24 months
|
|
Gastrointestinal disorders
Stomatitis
|
12.0%
25/209 • 24 months
|
31.2%
5/16 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
12.0%
25/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Gastrointestinal disorders
Constipation
|
12.0%
25/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Gastrointestinal disorders
Dyspepsia
|
12.0%
25/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.1%
17/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Dry mouth
|
7.2%
15/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.2%
13/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
General disorders
Fatigue
|
38.8%
81/209 • 24 months
|
81.2%
13/16 • 24 months
|
|
General disorders
Oedema peripheral
|
8.1%
17/209 • 24 months
|
31.2%
5/16 • 24 months
|
|
General disorders
Asthenia
|
9.1%
19/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
General disorders
Pain
|
7.2%
15/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Non-cardiac chest pain
|
5.7%
12/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
16/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Infections and infestations
Urinary tract infection
|
6.2%
13/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
23.0%
48/209 • 24 months
|
37.5%
6/16 • 24 months
|
|
Metabolism and nutrition disorders
Dehydration
|
6.7%
14/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.7%
14/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.3%
11/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.8%
31/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.9%
27/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.9%
27/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.2%
13/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Nervous system disorders
Headache
|
20.6%
43/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Nervous system disorders
Dizziness
|
12.0%
25/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Nervous system disorders
Dysgeusia
|
6.7%
14/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.8%
8/209 • 24 months
|
37.5%
6/16 • 24 months
|
|
Psychiatric disorders
Anxiety
|
8.6%
18/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Psychiatric disorders
Insomnia
|
7.7%
16/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Psychiatric disorders
Depression
|
5.3%
11/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Renal and urinary disorders
Proteinuria
|
8.6%
18/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
24.4%
51/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.4%
28/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.4%
26/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.1%
19/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
12.4%
26/209 • 24 months
|
31.2%
5/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.3%
9/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Vascular disorders
Hypertension
|
42.1%
88/209 • 24 months
|
50.0%
8/16 • 24 months
|
|
Investigations
Weight decreased
|
14.8%
31/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.96%
2/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.9%
6/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Eye disorders
Cataract
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Eye disorders
Lacrimation increased
|
0.96%
2/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Eye disorders
Eye swelling
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Eye disorders
Visual impairment
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Oral pain
|
5.3%
11/209 • 24 months
|
0.00%
0/16 • 24 months
|
|
Gastrointestinal disorders
Abdominal distension
|
3.3%
7/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Pancreatitis
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Toothache
|
1.4%
3/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.00%
0/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Gastrointestinal disorders
Haematochezia
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Tongue ulceration
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Abdominal mass
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Gastrointestinal sounds abnormal
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Pyrexia
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Malaise
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Disease progression
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Early satiety
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
General disorders
Impaired healing
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.96%
2/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.96%
2/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Hepatobiliary disorders
Gallbladder enlargement
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Nasopharyngitis
|
3.8%
8/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Oral herpes
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Cellulitis
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Folliculitis
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Liver abscess
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Influenza
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Infected cyst
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Infections and infestations
Tinea cruris
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Injury, poisoning and procedural complications
Contusion
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Lipase increased
|
4.3%
9/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Blood thyroid stimulating hormone increased
|
2.4%
5/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Investigations
Prothrombin time prolonged
|
0.00%
0/209 • 24 months
|
25.0%
4/16 • 24 months
|
|
Investigations
International normalised ratio increased
|
0.00%
0/209 • 24 months
|
18.8%
3/16 • 24 months
|
|
Investigations
Neutrophil count decreased
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Investigations
Low density lipoprotein increased
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Alanine aminotransferase decreased
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Aspartate aminotransferase decreased
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Blood bilirubin unconjugated increased
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Blood uric acid increased
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Carbon dioxide increased
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Liver function test abnormal
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Investigations
Protein total decreased
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.4%
5/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
1.9%
4/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
1.9%
4/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.3%
9/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.8%
10/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
1.9%
4/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.48%
1/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Nervous system disorders
Dizziness postural
|
1.9%
4/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Nervous system disorders
Paraesthesia
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Nervous system disorders
Hyperaesthesia
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Nervous system disorders
Vocal cord paralysis
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Psychiatric disorders
Withdrawal syndrome
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Renal and urinary disorders
Haematuria
|
2.4%
5/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Renal and urinary disorders
Nocturia
|
0.48%
1/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Renal and urinary disorders
Urethral atrophy
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Reproductive system and breast disorders
Breast mass
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.3%
9/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.4%
5/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Choking sensation
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal ulcer
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.8%
8/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.3%
9/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.3%
7/209 • 24 months
|
12.5%
2/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.48%
1/209 • 24 months
|
31.2%
5/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
1.4%
3/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.48%
1/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Neurodermatitis
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Vascular disorders
Deep vein thrombosis
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Vascular disorders
Flushing
|
0.96%
2/209 • 24 months
|
6.2%
1/16 • 24 months
|
|
Vascular disorders
Vena cava thrombosis
|
0.00%
0/209 • 24 months
|
6.2%
1/16 • 24 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place