105GM201: A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma

• Sponsor: Tracon Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01564914
• Collaborator: The Cleveland Clinic (Other), Case Comprehensive Cancer Center (Other)
• Enrollment: 22
• Locations: 4
• Arm: 1
• Duration (Months): 37
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy)

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma; Glioblastoma Multiforme	Drug: TRC105; Drug: Bevacizumab	Phase 2

Detailed Description

Angiogenesis plays a central role in the progression of solid cancer. TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on proliferating endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models. TRC105 has been well tolerated in patients with glioblastoma (GBM) as a single agent. The combination of TRC105 in combination with bevacizumab has demonstrated activity in bevacizumab refractory cancer patients. We hypothesize that TRC105 when administered with bevacizumab will have activity in GBM patients who progress on bevacizumab. By targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibition by bevacizumab, which could represent a major advance in GBM therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A total of 6 initial patients were treated with 10 mg/kg of TRC105 monotherapy. All patients progressed within 2 months of initiating treatment, reflecting the rapid progression. Due to the lack of activity in this disease setting with TRC105 alone, the study was amended to treat patients with 10 mg/kg TRC105 weekly in combination with 10 mg/kg bevacizumab every two weeks.A total of 6 initial patients were treated with 10 mg/kg of TRC105 monotherapy. All patients progressed within 2 months of initiating treatment, reflecting the rapid progression. Due to the lack of activity in this disease setting with TRC105 alone, the study was amended to treat patients with 10 mg/kg TRC105 weekly in combination with 10 mg/kg bevacizumab every two weeks.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab for the Treatment Of Recurrent or Progressive Glioblastoma That Has Progressed on Bevacizumab
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TRC105, Bevacizumab Single arm study	Drug: TRC105; 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle; Other Names: carotuximab ; Drug: Bevacizumab; IV; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Median Overall Survival (OS) [6 Months]

   Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial

Secondary Outcome Measures

1. Median Duration That Patients Remained Progression Free on Study [Patients are scanned every 8 weeks for approximately 6 months]

   The median number of months that patients remained progression free was calculated using modified RANO criteria to determine progression. Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.

2. Number of Participants With Adverse Events [Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months]

   Adverse event frequency per patient according to CTCAE version 4.0.

3. Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)). [Patients are scanned every 8 weeks]

   Number of patients who respond to study treatment according to modified RANO criteria was calculated (Objective Response Rate (ORR)). Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients with histologically confirmed glioblastoma, recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.

2. Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma.

3. Patients with up to 3 prior recurrences are allowed.

4. Karnofsky performance status ≥ 70%.

5. Age ≥ 18 years old.

6. Normal organ function

Exclusion Criteria:

• Patients who have had previous treatment with TRC105.

• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury

• Patients with cirrhosis, or active viral or nonviral hepatitis.

• Patients with active bleeding or pathologic conditions that carry a high risk of bleeding,(i.e. hereditary hemorrhagic telangiectasia).

• Patients who are currently receiving anticoagulation treatment

• Patients unwilling or unable to comply with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati	Cincinnati	Ohio	United States	45267
2	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
3	Cleveland Clinic	Cleveland	Ohio	United States	44195
4	Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Tracon Pharmaceuticals Inc.
• The Cleveland Clinic
• Case Comprehensive Cancer Center

Investigators

• Study Director: Charles Theuer, MD PhD, Tracon Pharmaceuticals Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tracon Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT01564914
• Other Study ID Numbers: 105GM201/Case 1312
• First Posted: Mar 28, 2012
• Last Update Posted: Jun 12, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Glioblastoma; Bevacizumab

Study Results

Participant Flow

Recruitment Details	Patients were screened and enrolled at 4 sites

Arm/Group Title	Carotuximab (TRC105), Bevacizumab	Carotuximab (TRC105)
Arm/Group Description	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Period Title: Overall Study
STARTED	16	6
COMPLETED	16	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	TRC105, Bevacizumab	TRC105	Total
Arm/Group Description	Single arm study TRC105: 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Single arm TRC105: 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle	Total of all reporting groups
Overall Participants	16	6	22
Age, Customized (years) [Median (Full Range) ]
Age	64.5	56.5	62
Sex: Female, Male (Count of Participants)
Female	3 18.8%	3 50%	6 27.3%
Male	13 81.3%	3 50%	16 72.7%
Screening Karnofsky Score (participants) [Number]
Score = 60: requires occasional assistance	1 6.3%	3 50%	4 18.2%
Score = 70: Can care for self; not normal activity	4 25%	0 0%	4 18.2%
Score = 80: Normal activity with effort	8 50%	2 33.3%	10 45.5%
Score = 90: Normal activities, minor symptoms.	3 18.8%	1 16.7%	4 18.2%
Cancer Histology (Count of Participants)
Glioblastoma	15 93.8%	5 83.3%	20 90.9%
Giant Cell Glioblastoma	1 6.3%	0 0%	1 4.5%
Astrocytoma	0 0%	1 16.7%	1 4.5%
Number of Prior Regimens (prior regimens) [Median (Full Range) ]
Median (Full Range) [prior regimens]	2.5	3	3

Outcome Measures

1. Primary Outcome

Title	Median Overall Survival (OS)
Description	Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

Patients treated with TRC105 and bevacizumab who expired. Overall survival was not captured in the monotherapy portion of the study.

Arm/Group Title	Carotuximab (TRC105), Bevacizumab
Arm/Group Description	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks
Measure Participants	1
Median (95% Confidence Interval) [months]	5.75

2. Secondary Outcome

Title	Median Duration That Patients Remained Progression Free on Study
Description	The median number of months that patients remained progression free was calculated using modified RANO criteria to determine progression. Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.
Time Frame	Patients are scanned every 8 weeks for approximately 6 months

Outcome Measure Data

Analysis Population Description

Patients with at least 1 on study scan were included in the efficacy population. The number of months that patients remained progression free was calculated for 5 evaluable monotherapy patients and 14 evaluable combination therapy patients.

Arm/Group Title	Carotuximab (TRC105), Bevacizumab	Carotuximab (TRC105)
Arm/Group Description	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Measure Participants	14	5
Median (95% Confidence Interval) [months]	1.81	1.38

3. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Adverse event frequency per patient according to CTCAE version 4.0.
Time Frame	Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months

Outcome Measure Data

Analysis Population Description

Patients who received at least a portion of a dose of TRC105 and/or Bevacizumab

Arm/Group Title	Carotuximab (TRC105), Bevacizumab	Carotuximab (TRC105)
Arm/Group Description	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every two weeks	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Measure Participants	16	6
Total SAEs	6 37.5%	3 50%
TRC105 Related SAEs	2 12.5%	0 0%

4. Secondary Outcome

Title	Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).
Description	Number of patients who respond to study treatment according to modified RANO criteria was calculated (Objective Response Rate (ORR)). Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.
Time Frame	Patients are scanned every 8 weeks

Outcome Measure Data

Analysis Population Description

Nineteen patients had measurable disease at baseline and received at least one follow up scan and were evaluable for the secondary efficacy outcome measure of PFS by modified RANO criteria. None of the patients treated on this study had a reduction in tumor burden compared to baseline.

Arm/Group Title	Carotuximab (TRC105), Bevacizumab	Carotuximab (TRC105) Alone
Arm/Group Description	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	TRC105 alone 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Measure Participants	16	6
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Arm/Group Title	Carotuximab (TRC105), Bevacizumab		Carotuximab (TRC105)
Arm/Group Description	Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks		Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
All Cause Mortality
	Carotuximab (TRC105), Bevacizumab		Carotuximab (TRC105)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		1/6 (16.7%)
Serious Adverse Events
	Carotuximab (TRC105), Bevacizumab		Carotuximab (TRC105)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)		3/6 (50%)
Blood and lymphatic system disorders
Anemia	1/16 (6.3%)	1	0/6 (0%)	0
General disorders
Disease Progression	1/16 (6.3%)	1	1/6 (16.7%)	1
Peripheral Oedema	1/16 (6.3%)	1	0/6 (0%)	0
Infections and infestations
Periorbital Cellulitis	1/16 (6.3%)	1	0/6 (0%)	0
Nervous system disorders
Aphasia	1/16 (6.3%)	1	0/6 (0%)	0
Cognitive Disorder	0/16 (0%)	0	1/6 (16.7%)	1
Convulsion	1/16 (6.3%)	1	2/6 (33.3%)	2
Mental Impairment	1/16 (6.3%)	1	0/6 (0%)	0
Transient Ischemic Attack	1/16 (6.3%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1	0/6 (0%)	0
Hypoxia	1/16 (6.3%)	1	0/6 (0%)	0
Vascular disorders
Embolism	1/16 (6.3%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Carotuximab (TRC105), Bevacizumab		Carotuximab (TRC105)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/16 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anaemia	3/16 (18.8%)	5	0/6 (0%)	0
Lymphopenia	2/16 (12.5%)	5	0/6 (0%)	0
Cardiac disorders
Tachycardia	1/16 (6.3%)	1	0/6 (0%)	0
Tachycardia	0/16 (0%)	0	1/6 (16.7%)	1
Ear and labyrinth disorders
Tinnitus	1/16 (6.3%)	1	0/6 (0%)	0
Endocrine disorders
Cushingoid	1/16 (6.3%)	1	0/6 (0%)	0
Eye disorders
Optic Neuropathy	1/16 (6.3%)	1	0/6 (0%)	0
Photophobia	0/16 (0%)	0	1/6 (16.7%)	1
Visual Impairment	1/16 (6.3%)	1	0/6 (0%)	0
Gastrointestinal disorders
Abdominal Distension	1/16 (6.3%)	1	0/6 (0%)	0
Abdominal Pain	1/16 (6.3%)	1	0/6 (0%)	0
Breath Odour	1/16 (6.3%)	1	0/6 (0%)	0
Constipation	3/16 (18.8%)	3	0/6 (0%)	0
Defeacation Urgency	1/16 (6.3%)	1	0/6 (0%)	0
Diarrhoea	6/16 (37.5%)	7	0/6 (0%)	0
Dry Mouth	1/16 (6.3%)	1	0/6 (0%)	0
Faecal Incontinence	2/16 (12.5%)	2	0/6 (0%)	0
Gingival Pain	1/16 (6.3%)	2	0/6 (0%)	0
Melaena	1/16 (6.3%)	1	0/6 (0%)	0
Nausea	2/16 (12.5%)	2	1/6 (16.7%)	2
Oral Pain	2/16 (12.5%)	2	0/6 (0%)	0
Periodontitis	1/16 (6.3%)	1	0/6 (0%)	0
Stomatitis	1/16 (6.3%)	2	0/6 (0%)	0
Tooth Impacted	1/16 (6.3%)	1	0/6 (0%)	0
Toothache	1/16 (6.3%)	2	0/6 (0%)	0
Vomiting	3/16 (18.8%)	3	0/6 (0%)	0
General disorders
Asthenia	4/16 (25%)	4	1/6 (16.7%)	1
Chest Pain	1/16 (6.3%)	1	0/6 (0%)	0
Chills	2/16 (12.5%)	2	0/6 (0%)	0
Disease Progression	1/16 (6.3%)	1	1/6 (16.7%)	1
Fatigue	12/16 (75%)	15	5/6 (83.3%)	5
Feeling Hot	1/16 (6.3%)	1	0/6 (0%)	0
Gait Disturbance	6/16 (37.5%)	8	0/6 (0%)	0
Infusion Site Extravasation	2/16 (12.5%)	2	0/6 (0%)	0
Localised Oedema	1/16 (6.3%)	1	0/6 (0%)	0
Malaise	2/16 (12.5%)	2	0/6 (0%)	0
Mucosal Inflammation	1/16 (6.3%)	1	0/6 (0%)	0
Oedema Peripheral	2/16 (12.5%)	5	0/6 (0%)	0
Pyrexia	2/16 (12.5%)	3	0/6 (0%)	0
Infections and infestations
Periorbital Cellulitis	1/16 (6.3%)	1	0/6 (0%)	0
Sinusitis	1/16 (6.3%)	1	0/6 (0%)	0
Upper Respiratory Tract Infection	4/16 (25%)	4	0/6 (0%)	0
Urinary Tract Infection	1/16 (6.3%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Back Pain	1/16 (6.3%)	1	0/6 (0%)	0
Contusion	2/16 (12.5%)	2	0/6 (0%)	0
Fall	4/16 (25%)	6	0/6 (0%)	0
Head Injury	1/16 (6.3%)	1	0/6 (0%)	0
Infusion Related Reaction	2/16 (12.5%)	2	0/6 (0%)	0
Limb Injury	1/16 (6.3%)	1	0/6 (0%)	0
Investigations
Alanine Aminotransferase Increased	2/16 (12.5%)	2	1/6 (16.7%)	1
Aspartate Aminotransferase Increased	0/16 (0%)	0	1/6 (16.7%)	1
Cardiac Murmur	1/16 (6.3%)	1	0/6 (0%)	0
Haemoglobin Decreased	1/16 (6.3%)	2	0/6 (0%)	0
Lipase Increased	1/16 (6.3%)	2	0/6 (0%)	0
Lymphocyte Count Decreased	1/16 (6.3%)	1	0/6 (0%)	0
Platelet Count Decreased	1/16 (6.3%)	1	0/6 (0%)	0
Weight Decreased	2/16 (12.5%)	4	0/6 (0%)	0
Metabolism and nutrition disorders
Decreased Appetite	5/16 (31.3%)	6	0/6 (0%)	0
Hyperglycaemia	2/16 (12.5%)	2	0/6 (0%)	0
Hypocalcaemia	1/16 (6.3%)	2	1/6 (16.7%)	2
Hypokalaemia	6/16 (37.5%)	13	0/6 (0%)	0
Hypophosphataemia	1/16 (6.3%)	1	0/6 (0%)	0
Vitamin D Deficiency	1/16 (6.3%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/16 (12.5%)	2	0/6 (0%)	0
Bursitis	1/16 (6.3%)	1	0/6 (0%)	0
Joint Stiffness	1/16 (6.3%)	1	0/6 (0%)	0
Muscle Spasms	1/16 (6.3%)	1	0/6 (0%)	0
Muscular Weakness	3/16 (18.8%)	5	2/6 (33.3%)	3
Pain in extremity	1/16 (6.3%)	1	1/6 (16.7%)	1
Nervous system disorders
Amnesia	2/16 (12.5%)	2	0/6 (0%)	0
Aphasia	2/16 (12.5%)	4	4/6 (66.7%)	5
Apraxia	1/16 (6.3%)	1	0/6 (0%)	0
Balance Disorder	0/16 (0%)	0	1/6 (16.7%)	1
Clumsiness	1/16 (6.3%)	1	0/6 (0%)	0
Cognitive Disorder	5/16 (31.3%)	6	2/6 (33.3%)	3
Convulsion	4/16 (25%)	4	3/6 (50%)	3
Coordination Abnormal	1/16 (6.3%)	1	0/6 (0%)	0
Disturbance in Attention	1/16 (6.3%)	1	1/6 (16.7%)	2
Dizziness	4/16 (25%)	5	0/6 (0%)	0
Dysarthria	1/16 (6.3%)	1	0/6 (0%)	0
Dysgeusia	1/16 (6.3%)	1	0/6 (0%)	0
Headache	10/16 (62.5%)	15	3/6 (50%)	10
Hemianopia Homonymous	1/16 (6.3%)	1	0/6 (0%)	0
Hypersomnia	1/16 (6.3%)	1	0/6 (0%)	0
Hypogeusia	1/16 (6.3%)	1	0/6 (0%)	0
Lethargy	0/16 (0%)	0	1/6 (16.7%)	1
Loss of Consciousness	1/16 (6.3%)	1	0/6 (0%)	0
Loss of Proprioception	1/16 (6.3%)	1	0/6 (0%)	0
Memory Impairment	2/16 (12.5%)	2	1/6 (16.7%)	1
Mental Impairment	1/16 (6.3%)	1	0/6 (0%)	0
Migraine	0/16 (0%)	0	1/6 (16.7%)	1
Neurological Symptom	1/16 (6.3%)	1	0/6 (0%)	0
Neuropathy Peripheral	1/16 (6.3%)	1	0/6 (0%)	0
Somnolence	1/16 (6.3%)	1	0/6 (0%)	0
Transient Ischaemic Attack	1/16 (6.3%)	1	0/6 (0%)	0
Tremor	3/16 (18.8%)	3	0/6 (0%)	0
VIIth Nerve Paralysis	2/16 (12.5%)	2	1/6 (16.7%)	2
Psychiatric disorders
Anxiety	2/16 (12.5%)	2	0/6 (0%)	0
Depression	0/16 (0%)	0	1/6 (16.7%)	1
Disorientation	0/16 (0%)	0	1/6 (16.7%)	1
Flat Affect	1/16 (6.3%)	1	0/6 (0%)	0
Hallucination, visual	1/16 (6.3%)	1	0/6 (0%)	0
Insomnia	1/16 (6.3%)	1	1/6 (16.7%)	1
Renal and urinary disorders
Bilirubinuria	1/16 (6.3%)	1	0/6 (0%)	0
Haematuria	1/16 (6.3%)	1	0/6 (0%)	0
Micturition Urgency	1/16 (6.3%)	1	0/6 (0%)	0
Pollakiuria	1/16 (6.3%)	1	0/6 (0%)	0
Proteinuria	1/16 (6.3%)	1	0/6 (0%)	0
Renal Failure Acute	1/16 (6.3%)	1	0/6 (0%)	0
Renal cyst	1/16 (6.3%)	1	0/6 (0%)	0
Urinary Incontinence	2/16 (12.5%)	2	1/6 (16.7%)	1
Urinary Retention	1/16 (6.3%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/16 (12.5%)	2	0/6 (0%)	0
Dysphonia	1/16 (6.3%)	1	0/6 (0%)	0
Dyspnoea	3/16 (18.8%)	3	0/6 (0%)	0
Hypoxia	2/16 (12.5%)	2	0/6 (0%)	0
Nasal Congestion	2/16 (12.5%)	2	0/6 (0%)	0
Nasal Discomfort	1/16 (6.3%)	1	0/6 (0%)	0
Oropharyngeal Pain	1/16 (6.3%)	1	0/6 (0%)	0
Pleural Effusion	1/16 (6.3%)	1	0/6 (0%)	0
Respiratory Tract Congestion	1/16 (6.3%)	1	0/6 (0%)	0
Rhinorrhoea	1/16 (6.3%)	1	0/6 (0%)	0
Sinus Congestion	1/16 (6.3%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis Acneiform	2/16 (12.5%)	2	0/6 (0%)	0
Ecchymosis	1/16 (6.3%)	1	0/6 (0%)	0
Onychoclasis	1/16 (6.3%)	1	0/6 (0%)	0
Petechiae	1/16 (6.3%)	1	0/6 (0%)	0
Rash	3/16 (18.8%)	3	0/6 (0%)	0
Skin Irritation	1/16 (6.3%)	1	0/6 (0%)	0
Vascular disorders
Embolism	2/16 (12.5%)	2	0/6 (0%)	0
Epistaxis	11/16 (68.8%)	14	1/6 (16.7%)	1
Flushing	3/16 (18.8%)	3	0/6 (0%)	0
Gingival Bleeding	4/16 (25%)	4	1/6 (16.7%)	1
Haemoptysis	1/16 (6.3%)	1	0/6 (0%)	0
Hypertension	3/16 (18.8%)	3	0/6 (0%)	0
Telangiectasia	0/16 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.