Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma

• Sponsor: Mirati Therapeutics Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03680521
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 55
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma	Drug: Sitravatinib; Drug: Nivolumab	Phase 2

Detailed Description

Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of nivolumab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma
• Actual Study Start Date: Oct 10, 2018
• Actual Primary Completion Date: Apr 27, 2020
• Anticipated Study Completion Date: May 11, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sitravatinib and nivolumab Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.	Drug: Sitravatinib; Sitravatinib oral capsule administered daily for 6-8 weeks in segments 1 and 2.; Drug: Nivolumab; Nivolumab administered as 240 mg IV every 2 weeks for 4-6 weeks in segment 2.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

   Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions.

2. Point in Time Objective Response Prior to Surgery [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

   Number and percentage of participants who experienced a response prior to surgery in accordance with RECIST 1.1. CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions; Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD); PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.

Secondary Outcome Measures

1. Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) [Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)]

   TEAEs occured after the first dose of any study treatment or any preexisting condition that increased in severity after the first dose of study treatment and prior to 28 days after last dose of study drug or surgery, whichever occurred last. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

2. Blood Plasma Concentrations of Sitravatinib [Day 1 (pre-dose, and 30 minutes to 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)]

3. Time to Surgery [Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)]

   Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.

4. Disease Free Survival (DFS) [Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)]

   DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.

5. Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

6. Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

7. Change From Baseline in Regulatory T-cells (Tregs) in the Tumor [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

8. Change From Baseline in CD4+ T-cells in the Tumor [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

9. Change From Baseline in CD8+ T-cells in the Tumor [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

10. Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor [Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)]

11. Change From Baseline of Selected Cytokines in Peripheral Blood [Baseline to Day 43]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Imaging results consistent with locally-advanced RCC

2. Candidate for partial or complete nephrectomy as part of treatment plan.

3. Measurable disease per RECIST version 1.1.

4. ECOG performance status 0 or 1.

5. Adequate bone marrow and organ function.

Exclusion Criteria:

1. Prior systemic anti-tumor treatment for RCC.

2. Patients who are receiving any other investigational agents.

3. Clinical status indicating that immediate surgery (within 6 weeks) is warranted regardless of whether neoadjuvant therapy is to be administered, as assessed by the treating surgeon.

4. Inability to undergo baseline tumor biopsy.

5. Active or prior documented autoimmune or immunocompromising conditions.

6. Uncontrolled hypertension.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Mirati Therapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 16, 2018
• Statistical Analysis Plan - Jul 1, 2020

More Information

Publications

None provided.

• Responsible Party: Mirati Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03680521
• Other Study ID Numbers: 516-002
• First Posted: Sep 21, 2018
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mirati Therapeutics Inc.: ccRCC; MGCD516; Antineoplastic Agents; Immunologic factors; nivolumab; Tyrosine Kinase Inhibitor; VEGFR; TAM RTKs; PD-1; PD-L1
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Nivolumab

Study Results

Participant Flow

Pre-assignment Detail	After the participants completed screening, participants underwent an initial diagnostic tumor biopsy of their renal lesion. Out of the 25 participants enrolled, 5 participants did not receive treatment per protocol. The reasons were ineligible histology (3), disallowed concomitant treatment (1), and patient noncompliance (1).

Arm/Group Title	Sitravatinib 120 mg	Sitravatinib 80 mg
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).
Period Title: Overall Study
STARTED	7	13
COMPLETED	0	2
NOT COMPLETED	7	11

Baseline Characteristics

Arm/Group Title	Sitravatinib 120 mg	Sitravatinib 80 mg	Total
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Total of all reporting groups
Overall Participants	7	13	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (6.19)	56.7 (12.70)	59.1 (11.18)
Sex: Female, Male (Count of Participants)
Female	2 28.6%	2 15.4%	4 20%
Male	5 71.4%	11 84.6%	16 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 14.3%	3 23.1%	4 20%
Not Hispanic or Latino	6 85.7%	9 69.2%	15 75%
Unknown or Not Reported	0 0%	1 7.7%	1 5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	7 100%	12 92.3%	19 95%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 7.7%	1 5%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0	7 100%	12 92.3%	19 95%
1	0 0%	1 7.7%	1 5%
Clinical TNM Staging at Diagnosis (Count of Participants)
T2bN0M0	1 14.3%	0 0%	1 5%
T3N0M0	0 0%	1 7.7%	1 5%
T3N0M1	0 0%	1 7.7%	1 5%
T3NXM0	0 0%	1 7.7%	1 5%
T3aN0M0	6 85.7%	2 15.4%	8 40%
T3aNXM0	0 0%	7 53.8%	7 35%
T3aNXM1	0 0%	1 7.7%	1 5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery
Description	Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

Clinical activity evaluable population: All participants who 1) had measurable disease (per RECIST 1.1) at baseline, 2) received at least one dose of both sitravatinib and nivolumab, 3) had their onstudy disease assessment prior to surgery, and 4) underwent surgery and were deemed disease-free (i.e. non-metastatic) after surgery.

Arm/Group Title	Sitravatinib 120 mg	Sitravatinib 80 mg
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).
Measure Participants	6	11
Count of Participants [Participants]	2 28.6%	0 0%

2. Secondary Outcome

Title	Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Description	TEAEs occured after the first dose of any study treatment or any preexisting condition that increased in severity after the first dose of study treatment and prior to 28 days after last dose of study drug or surgery, whichever occurred last. TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame	Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)

Outcome Measure Data

Analysis Population Description

Safety population: all participants who received at least 1 dose of either sitravatinib or nivolumab.

Arm/Group Title	Sitravatinib 120 mg	Sitravatinib 80 mg
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).
Measure Participants	7	13
Count of Participants [Participants]	7 100%	13 100%

3. Secondary Outcome

Title	Blood Plasma Concentrations of Sitravatinib
Time Frame	Day 1 (pre-dose, and 30 minutes to 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)

Outcome Measure Data

Analysis Population Description

Pharmacokinetics (PK) evaluable population: all participants who received treatment with sitravatinib and had non-missing concentration-time data. Concentration was assessed by actual dose associated with each time-point.

Arm/Group Title	PK Population: Sitravatinib 120 mg	PK Population: Sitravatinib 80 mg	PK Population: Sitravatinib 60 mg
Arm/Group Description	PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 120 mg of sitravatinib orally.	PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 80 mg of sitravatinib orally.	PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 60 mg of sitravatinib orally.
Measure Participants	7	13	1
Day 1 (pre-dose)	0.0 (0.00)	0.6 (2.27)
Day 1 (30 mins post-dose)	2.9 (2.12)	1.0 (1.17)
Day 1 (4 hours post-dose)	17.0 (10.38)	13.7 (10.60)
Day 15 (pre-dose)	87.7 (9.62)	63.3 (42.36)
Day 43 (pre-dose)	75.0 (23.74)	53.7 (32.88)	66.5 (NA)

4. Secondary Outcome

Title	Time to Surgery
Description	Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.
Time Frame	Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

Clinical activity evaluable population: All participants who 1) had measurable disease (per RECIST 1.1) at baseline, 2) received at least one dose of both sitravatinib and nivolumab, 3) had their onstudy disease assessment prior to surgery, and 4) underwent surgery and were deemed disease-free after surgery.

Arm/Group Title	Sitravatinib 120 mg	Sitravatinib 80 mg
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).
Measure Participants	6	11
Time to Surgery	56.5	50.0
Delays in Surgery	1.0	1.0

5. Secondary Outcome

Title	Disease Free Survival (DFS)
Description	DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.
Time Frame	Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Change From Baseline in Regulatory T-cells (Tregs) in the Tumor
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change From Baseline in CD4+ T-cells in the Tumor
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Change From Baseline in CD8+ T-cells in the Tumor
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Change From Baseline of Selected Cytokines in Peripheral Blood
Time Frame	Baseline to Day 43

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Primary Outcome

Title	Point in Time Objective Response Prior to Surgery
Description	Number and percentage of participants who experienced a response prior to surgery in accordance with RECIST 1.1. CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions; Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD); PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.
Time Frame	Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Outcome Measure Data

Analysis Population Description

Clinical activity evaluable population: All participants who 1) had measurable disease (per RECIST 1.1) at baseline, 2) received at least one dose of both sitravatinib and nivolumab, 3) had their onstudy disease assessment prior to surgery, and 4) underwent surgery and were deemed disease-free (i.e. non-metastatic) after surgery.

Arm/Group Title	Sitravatinib 120 mg	Sitravatinib 80 mg
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).	Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).
Measure Participants	6	11
Preoperative timepoint response: CR	0 0%	0 0%
Preoperative timepoint response: PR	2 28.6%	0 0%
Preoperative timepoint response: SD	4 57.1%	11 84.6%
Preoperative timepoint response: PD	0 0%	0 0%

Adverse Events

Time Frame	Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Arm/Group Title	Sitravatinib 120 mg		Sitravatinib 80 mg
Arm/Group Description	Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).		Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).
All Cause Mortality
	Sitravatinib 120 mg		Sitravatinib 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/13 (0%)
Serious Adverse Events
	Sitravatinib 120 mg		Sitravatinib 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		1/13 (7.7%)
Cardiac disorders
Atrial fibrillation	1/7 (14.3%)		0/13 (0%)
Infections and infestations
Atypical pneumonia	0/7 (0%)		1/13 (7.7%)
Sepsis	0/7 (0%)		1/13 (7.7%)
Urosepsis	1/7 (14.3%)		0/13 (0%)
Renal and urinary disorders
Urinary retention	1/7 (14.3%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/7 (0%)		1/13 (7.7%)
Vascular disorders
Deep vein thrombosis	0/7 (0%)		1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Sitravatinib 120 mg		Sitravatinib 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		13/13 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/7 (14.3%)		0/13 (0%)
Cardiac disorders
Atrial fibrillation	0/7 (0%)		1/13 (7.7%)
Tachycardia	0/7 (0%)		1/13 (7.7%)
Ear and labyrinth disorders
Hypoacusis	0/7 (0%)		1/13 (7.7%)
Tinnitus	1/7 (14.3%)		0/13 (0%)
Endocrine disorders
Hypothyroidism	2/7 (28.6%)		0/13 (0%)
Thyroiditis	0/7 (0%)		2/13 (15.4%)
Eye disorders
Visual impairment	0/7 (0%)		1/13 (7.7%)
Gastrointestinal disorders
Diarrhoea	2/7 (28.6%)		6/13 (46.2%)
Constipation	3/7 (42.9%)		3/13 (23.1%)
Nausea	1/7 (14.3%)		3/13 (23.1%)
Oral dysaesthesia	3/7 (42.9%)		0/13 (0%)
Glossodynia	0/7 (0%)		2/13 (15.4%)
Pancreatitis	0/7 (0%)		2/13 (15.4%)
Vomiting	2/7 (28.6%)		0/13 (0%)
Abdominal pain	1/7 (14.3%)		0/13 (0%)
Dental caries	0/7 (0%)		1/13 (7.7%)
Dry mouth	0/7 (0%)		1/13 (7.7%)
Dysphagia	0/7 (0%)		1/13 (7.7%)
Oral pain	0/7 (0%)		1/13 (7.7%)
General disorders
Fatigue	3/7 (42.9%)		7/13 (53.8%)
Pain	2/7 (28.6%)		0/13 (0%)
Chills	1/7 (14.3%)		0/13 (0%)
Pyrexia	1/7 (14.3%)		0/13 (0%)
Infections and infestations
Urinary tract infection	2/7 (28.6%)		0/13 (0%)
Herpes zoster	1/7 (14.3%)		0/13 (0%)
Influenza	0/7 (0%)		1/13 (7.7%)
Oral herpes	1/7 (14.3%)		0/13 (0%)
Rhinitis	0/7 (0%)		1/13 (7.7%)
Sinusitis	0/7 (0%)		1/13 (7.7%)
Tooth abscess	1/7 (14.3%)		0/13 (0%)
Injury, poisoning and procedural complications
Incision site erythema	0/7 (0%)		1/13 (7.7%)
Incision site vesicles	0/7 (0%)		1/13 (7.7%)
Procedural pain	1/7 (14.3%)		0/13 (0%)
Investigations
Alanine aminotransferase increased	1/7 (14.3%)		5/13 (38.5%)
Lipase increased	3/7 (42.9%)		3/13 (23.1%)
Amylase increased	2/7 (28.6%)		1/13 (7.7%)
Blood thyroid stimulating hormone increased	2/7 (28.6%)		1/13 (7.7%)
Aspartate aminotransferase increased	0/7 (0%)		2/13 (15.4%)
Weight decreased	1/7 (14.3%)		1/13 (7.7%)
Blood bilirubin increased	0/7 (0%)		1/13 (7.7%)
Haematocrit increased	0/7 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Decreased appetite	1/7 (14.3%)		2/13 (15.4%)
Hyperuricaemia	1/7 (14.3%)		0/13 (0%)
Hypoglycaemia	1/7 (14.3%)		0/13 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/7 (0%)		2/13 (15.4%)
Flank pain	1/7 (14.3%)		1/13 (7.7%)
Myalgia	2/7 (28.6%)		0/13 (0%)
Neck pain	0/7 (0%)		2/13 (15.4%)
Arthralgia	1/7 (14.3%)		0/13 (0%)
Bone pain	0/7 (0%)		1/13 (7.7%)
Musculoskeletal pain	1/7 (14.3%)		0/13 (0%)
Pain in jaw	1/7 (14.3%)		0/13 (0%)
Nervous system disorders
Headache	4/7 (57.1%)		3/13 (23.1%)
Dizziness	1/7 (14.3%)		2/13 (15.4%)
Hyperaesthesia	0/7 (0%)		2/13 (15.4%)
Memory impairment	1/7 (14.3%)		0/13 (0%)
Somnolence	1/7 (14.3%)		0/13 (0%)
Psychiatric disorders
Delirium	0/7 (0%)		1/13 (7.7%)
Renal and urinary disorders
Haematuria	1/7 (14.3%)		2/13 (15.4%)
Dysuria	0/7 (0%)		2/13 (15.4%)
Acute kidney injury	0/7 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	5/7 (71.4%)		6/13 (46.2%)
Acute respiratory failure	1/7 (14.3%)		1/13 (7.7%)
Cough	1/7 (14.3%)		1/13 (7.7%)
Epistaxis	1/7 (14.3%)		1/13 (7.7%)
Acute respiratory distress syndrome	0/7 (0%)		1/13 (7.7%)
Nasal congestion	1/7 (14.3%)		0/13 (0%)
Pneumonitis	1/7 (14.3%)		0/13 (0%)
Rhinitis allergic	1/7 (14.3%)		0/13 (0%)
Rhinorrhoea	1/7 (14.3%)		0/13 (0%)
Sinus congestion	1/7 (14.3%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Rash	1/7 (14.3%)		3/13 (23.1%)
Pruritus	0/7 (0%)		3/13 (23.1%)
Nail discolouration	1/7 (14.3%)		1/13 (7.7%)
Night sweats	1/7 (14.3%)		1/13 (7.7%)
Dry skin	0/7 (0%)		1/13 (7.7%)
Palmar-plantar erythrodysaesthesia syndrome	0/7 (0%)		1/13 (7.7%)
Psoriasis	0/7 (0%)		1/13 (7.7%)
Vascular disorders
Hypertension	6/7 (85.7%)		7/13 (53.8%)
Hypotension	2/7 (28.6%)		0/13 (0%)
Thrombophlebitis superficial	0/7 (0%)		1/13 (7.7%)

Limitations/Caveats

[Not Specified]

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.