A Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, in Patients With Advanced Solid Tumors

• Sponsor: Jubilant Innovation Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00842335
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study, the first clinical trial of JI-101, is to determine the maximum tolerated dose of JI-101 when given orally to patients with solid tumors. Safety, tolerability, pharmacokinetics, pharmacodynamics, and the effects of the drug on tumor metabolism will also be studied. JI-101 is an inhibitor of new blood vessel growth that may provide benefit to patients with solid tumors that have failed standard therapeutic regimens.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: JI-101	Phase 1/Phase 2

Detailed Description

JI-101 is a compound being developed for the treatment of patients with solid tumors; specifically patients for which no approved therapy or standard of care is available or have solid tumors and have failed standard of care therapy. JI-101 is an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRβ), and EphB4 receptor, each of which plays an important role in driving vascularization (angiogenesis and vasculogenesis) during normal development and tumorigenesis. JI-101 inhibits the growth of new blood vessels, which in turn, may slow or prevent the growth of tumors. The purpose of this open label study is to treat patients with advanced solid tumors, with increasing doses of JI-101, thereby providing information about the maximum tolerated dose (MTD). The study will also examine safety, tolerability, pharmacokinetics, pharmacodynamics, and may evaluate the effects of the drug on tumor metabolism. During this dose-escalation study, at least two patients will be dosed at each dose level (cohort). The patients must complete 21 days of dosing and safety results will be reviewed prior to any patients being assigned the next higher dose level. A continuous reassessment method will be utilized to escalate JI-101 doses between cohorts. Doses will be increased, with an anticipated high dose of 800mg per day. If the MTD is not reached, an optimal biologic dose (OBD) will be determined based on the highest doses that are tolerable with acceptable efficacy. The cohort at MTD or OBD will be expanded to include up to 30 patients with solid tumors to further explore the safety and tolerability of orally-administered JI-101.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JI-101	Drug: JI-101; JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of JI-101 [28 days (1 cycle)]

   The primary objective of this study was to determine the maximum tolerated dose (MTD) of JI-101 when administered orally in patients with advanced solid tumors. The MTD was established based on safety data from Cycle 1. Patients who completed 21 days of treatment in Cycle 1 were considered to have completed the study for the determination of MTD. Patients were eligible to continue treatment with JI-101 until they experienced disease progression or unacceptable treatment-related toxicity. Unacceptable treatment-related toxicity was defined as a clinically significant AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and that was attributed to JI 101.

Secondary Outcome Measures

1. Number of Participants Reaching Maximum Tolerated Dose [Up to 112 days (up to four 28-day cycles) or longer if the patient is benefiting from treatment]

   Number of participants withdrawn from study due to adverse events

2. Overall Clinical Response by Cycle [Up to 112 days ( four 28-day cycles)]

   Stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions

3. Days to Progression [Up to 112 days (four 28-day cycles) or longer if the patient is benefiting from treatment]

   Progression: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Be 18 years of age or greater at the time of consent.

• Have solid tumors for which no approved therapy or standard of care is available or have solid tumors and have failed standard-of-care therapy.

• Have life expectancy of greater than 3 months.

• Have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

• Have organ and marrow function as defined below:

• absolute neutrophil count ≥ 1.5 x 10^9 cells/L

• hemoglobin ≥ 9.0 g/dL

• platelets ≥ 75 x 10^9 cells/L

• total bilirubin ≤ 1.5 x upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5 x ULN for liver metastases)

• serum creatinine < 1.5 x ULN

• < 500 mg urinary protein/24 hours or dipstick < 2+

• No evidence of preexisting uncontrolled hypertension as documented by two baseline blood pressure readings taken at least 1 hour apart (the baseline systolic blood pressure readings must be <140 mm Hg, and the baseline diastolic blood pressure readings must be <90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible)

• Have no clinically significant disease that poses a risk to the patient and/or would interfere with study evaluations or procedures.

• Have within normal range cardiac function as measured by twelve-lead electrocardiogram at Screening.

• Be clinically euthyroid.

• If female, must be postmenopausal (at least 1 year from last menses), or surgically sterile, or if a female patient of childbearing potential they must agree to use acceptable methods of birth control, which include local double-barrier contraceptive methods, such as cervical diaphragm plus spermicide, female condom plus spermicide, or a non-hormonal intrauterine device (IUD) plus spermicide, or systemic contraceptive methods, such as oral, injectable, transdermal or implantable hormonal contraceptives (including hormone-containing IUDs) during the study period, and for 30 days after the last dose of study drug. Female patients of childbearing potential must have a negative serum pregnancy test within the 3 days before the first study drug administration. Male patients must be surgically sterile or also agree to use acceptable methods of birth control with their female partners, and this may include use of a male condom plus spermicide. If the subject is practicing abstinence at the time of Screening, he/she must agree to use a double-barrier contraceptive method if he/she becomes sexually active.

• Be able to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Be pregnant or breastfeeding.

• Have a known history of human immunodeficiency virus (HIV) infection because the effect of JI-101 on immunosuppression and drug interactions with anti-retroviral medications is unknown.

• Have participated in an investigational drug/device/biologic study within 30 days (or within 5 half-lives of the treatment, whichever is longer) before Visit 1 or who are currently participating in another investigational drug/device/biologic study. Participation in non-interventional or observational studies is allowed.

• Have a history of cardiac abnormalities including: abnormal and clinically relevant ECGs; frequent palpitations or syncopal episodes; heart failure; hypokalemia; stroke; family history of Long QT Syndrome; acute myocardial infarction or ventricular tachyarrhythmia within the previous 12 months.

• Have used concomitant medications that prolong the QT/QTc interval within 14 days prior to Day 1.

• Have a history of significant retinopathy or any progressive eye disease that could lead to severe loss of visual acuity or visual field loss during the study period.

• Have had therapeutic reanticoagulation with heparin or heparin analogs (low molecular weight heparins) or warfarin within the past 4 weeks. Low dose warfarin (1 to 2 mg/day) is allowed for prophylaxis treatment.

• Have had major surgery, radiotherapy, chemotherapy, or cytokine therapy within 4 weeks of treatment initiation. Patients must have recovered to baseline or grade 1 from any clinically significant adverse event experienced during those prior therapies.

• Have gastrointestinal abnormalities including inability to take oral medications, malabsorption syndromes or other clinically significant GI abnormalities that may impair the absorption of JI-101 in the opinion of the Investigator.

• Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would pose a risk to patient safety or that would limit compliance with study requirements.

• Have any condition that, in the opinion of the Investigator, would interfere with a patient's ability to perform the required activities of the study or would subject the patient to undue risk.

• Patients with proteinuria (patients with >2+ protein on urine dipstick) at baseline should undergo a 24-hour urine collection. Results must demonstrate <500 mg of protein in 24 hours to allow participation in the study)

• Patients with any of the following contraindications to FDG-PET can participate in the study if all of the inclusion criteria and none of the exclusion criteria are met, but these patients are excluded from FDG PET assessments:

o Inability to remain lying down in PET scanner (for PET portion of the study).

• Absence of at least one metastatic lesion greater than or equal to 2 cm on pre-dose CT (computed tomography) scan or other radiographic imaging as defined by response evaluation criteria in solid tumors (RECIST) criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Premiere Oncology of Arizona	Scottsdale	Arizona	United States	85258

Sponsors and Collaborators

• Jubilant Innovation Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jubilant Innovation Ltd.
• ClinicalTrials.gov Identifier: NCT00842335
• Other Study ID Numbers: JI-101-001
• First Posted: Feb 12, 2009
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Jubilant Innovation Ltd.: solid tumors; angiogenesis inhibitor; dose escalation; maximum tolerated dose; JI-101
• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Recruitment Details	This study was conducted at one clinical site in the US. First Patient Enrolled: 24 February 2009 Cut-off Date: 15 February 2011

Arm/Group Title	JI-101
Arm/Group Description	JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	JI-101
Arm/Group Description	JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 61.1%
>=65 years	7 38.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (9.11)
Sex: Female, Male (Count of Participants)
Female	10 55.6%
Male	8 44.4%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of JI-101
Description	The primary objective of this study was to determine the maximum tolerated dose (MTD) of JI-101 when administered orally in patients with advanced solid tumors. The MTD was established based on safety data from Cycle 1. Patients who completed 21 days of treatment in Cycle 1 were considered to have completed the study for the determination of MTD. Patients were eligible to continue treatment with JI-101 until they experienced disease progression or unacceptable treatment-related toxicity. Unacceptable treatment-related toxicity was defined as a clinically significant AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and that was attributed to JI 101.
Time Frame	28 days (1 cycle)

Outcome Measure Data

Analysis Population Description

Full Analysis Population (FAS) or Modified Intent-to-Treat (mITT) Population: All patients enrolled into the study who received JI-101 and completed at least 21 days of dosing in Cycle 1 comprised the FAS. Safety Population: Included all patients who received at least one dose of study drug. This population was used for all safety analyses.

Arm/Group Title	JI-101
Arm/Group Description	JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Measure Participants	18
Number [mg]	400

2. Secondary Outcome

Title	Number of Participants Reaching Maximum Tolerated Dose
Description	Number of participants withdrawn from study due to adverse events
Time Frame	Up to 112 days (up to four 28-day cycles) or longer if the patient is benefiting from treatment

Outcome Measure Data

Analysis Population Description

Only one subject withdrew due to an adverse event.

Arm/Group Title	All Subjects
Arm/Group Description	The starting dose of JI-101 for patients in the first cohort was 100 mg QD. All patients took JI-101 without food on Day 0, with a high fat meal on Day 2, and with a regular diet on Day 3 onwards. Patients in the first three cohorts were dosed QD. Based on PK characteristics observed from the first eight patients (Cohort 1, Cohort 2, and Cohort 3), subsequent cohorts were dosed BID. After the first eight patients, the combined PK profiles of the enrolled patients were studied. These assessments indicated that the PK profile for JI-101 supported BID dosing. Therefore, BID dosing was administered to patients who enrolled in the study following the effective date of Protocol
Measure Participants	18
Number [participants]	18 100%

3. Secondary Outcome

Title	Overall Clinical Response by Cycle
Description	Stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions
Time Frame	Up to 112 days ( four 28-day cycles)

Outcome Measure Data

Analysis Population Description

All 18 participants were analyzed.

Arm/Group Title	JI-101
Arm/Group Description	JI-101 : JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
Measure Participants	18
Cycle 2 - Stable Disease	7 38.9%
Cycle 2 - Progressive Disease	10 55.6%
Cycle 4 - Stable Disease	5 27.8%
Cycle 4 - Progressive Disease	2 11.1%
Cycle 6 - Stable Disease	5 27.8%
Cycle 6 - Progressive Disease	0 0%
Cycle 8 - Stable Disease	3 16.7%
Cycle 8 - Progressive Disease	2 11.1%
Cycle 10 - Stable Disease	2 11.1%
Cycle 10 - Progressive Disease	1 5.6%
Cycle 12 - Stable Disease	2 11.1%
Cycle 12 - Progressive Disease	0 0%
Cycle 14 - Stable Disease	1 5.6%
Cycle 14 - Progressive Disease	0 0%
Cycle 16 - Stable Disease	1 5.6%
Cycle 16 - Progressive Disease	0 0%

4. Secondary Outcome

Title	Days to Progression
Description	Progression: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions
Time Frame	Up to 112 days (four 28-day cycles) or longer if the patient is benefiting from treatment

Outcome Measure Data

Analysis Population Description

The efficacy analyses were performed using all patients, who had at least one post-treatment evaluation for tumor assessment (N=17). The overall response was based on the number of cycles of treatment before the participant experienced progressive disease.

Arm/Group Title	All Subjects
Arm/Group Description
Measure Participants	17
Median (Full Range) [days]	55

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	One subject was followed for an additional 5 months until the progression of disease.
Arm/Group Title	JI-101
Arm/Group Description	Maximum tolerated dose
All Cause Mortality
	JI-101
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	JI-101
	Affected / at Risk (%)	# Events
Total	6/18 (33.3%)
Gastrointestinal disorders
peritonitis	1/18 (5.6%)	1
duodenal obstruction	1/18 (5.6%)	1
impaired gastric emptying	1/18 (5.6%)	1
diarrhea	1/18 (5.6%)	1
Infections and infestations
pneumonia	1/18 (5.6%)	1
urinary tract infection	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
pathological fracture	1/18 (5.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
metastases to central nervous system	1/18 (5.6%)	1
Nervous system disorders
subarachnoid hemorrhage	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	1/18 (5.6%)	1
dyspnea exertional	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	JI-101
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Anemia	1/18 (5.6%)	1
Lymphadenopathy	1/18 (5.6%)	1
Lymph node pain	1/18 (5.6%)	1
Neutropenia	1/18 (5.6%)	1
Thrombocytopenia	1/18 (5.6%)	1
Cardiac disorders
Tachycardia	1/18 (5.6%)	1
Ear and labyrinth disorders
Ear discomfort	1/18 (5.6%)	1
Ear disorder	1/18 (5.6%)	1
Ear pain	2/18 (11.1%)	2
Hyperacusis	1/18 (5.6%)	1
Tinnitus	1/18 (5.6%)	1
Endocrine disorders
Hypothyroidism	4/18 (22.2%)	4
Eye disorders
Acquired corneal dystrophy	1/18 (5.6%)	1
Dellen	1/18 (5.6%)	1
Diplopia	1/18 (5.6%)	1
Dry eye	3/18 (16.7%)	3
Eye pain	1/18 (5.6%)	1
Intraocular pressure increased	2/18 (11.1%)	2
Macular degeneration	1/18 (5.6%)	1
Pseudoexfoliation of lens capsule	1/18 (5.6%)	1
Vision blurred	3/18 (16.7%)	3
Visual acuity reduced	1/18 (5.6%)	1
Gastrointestinal disorders
Abdominal distension	3/18 (16.7%)	3
Abdominal pain	2/18 (11.1%)	2
Abdominal tenderness	1/18 (5.6%)	1
Aphthous stomatitis	1/18 (5.6%)	1
Ascites	2/18 (11.1%)	2
Constipation	6/18 (33.3%)	6
Diarrhea	5/18 (27.8%)	5
Dry mouth	4/18 (22.2%)	4
Dyspepsia	1/18 (5.6%)	1
Eructation	1/18 (5.6%)	1
Flatulence	1/18 (5.6%)	1
Frequent bowel movements	1/18 (5.6%)	1
Gastroesophageal reflux disease	1/18 (5.6%)	1
Glossodynia	1/18 (5.6%)	1
Hematochezia	2/18 (11.1%)	2
Nausea	9/18 (50%)	9
Oral pain	2/18 (11.1%)	2
Pyrexia	1/18 (5.6%)	1
Retching	1/18 (5.6%)	1
Stomatitis	2/18 (11.1%)	2
Tongue blistering	1/18 (5.6%)	1
Vomiting	7/18 (38.9%)	7
General disorders
Asthenia	2/18 (11.1%)	2
Chills	5/18 (27.8%)	5
Edema peripheral	1/18 (5.6%)	1
Fatigue	11/18 (61.1%)	11
Feeling cold	1/18 (5.6%)	1
Gait disturbance	1/18 (5.6%)	1
Influenza like illness	1/18 (5.6%)	1
Mass	1/18 (5.6%)	1
Non-cardiac chest pain	4/18 (22.2%)	4
Pain	2/18 (11.1%)	2
Pyrexia	4/18 (22.2%)	4
Temperature intolerance	1/18 (5.6%)	1
Thirst	1/18 (5.6%)	1
Hepatobiliary disorders
Hyperbilirubinemia	2/18 (11.1%)	2
Infections and infestations
Clostridial infection	2/18 (11.1%)	2
Fungal infection	1/18 (5.6%)	1
Furuncle	1/18 (5.6%)	1
Nasal abscess	1/18 (5.6%)	1
Upper respiratory tract infection	1/18 (5.6%)	1
Urinary tract infection	2/18 (11.1%)	2
Vaginal abscess	1/18 (5.6%)	1
Vaginal infection	1/18 (5.6%)	1
Vulvovaginal mycotic infection	2/18 (11.1%)	2
Investigations
Activated partial thromboplastin time prolonged	2/18 (11.1%)	2
Alanine aminotransferase increased	3/18 (16.7%)	3
Aspartate aminotransferase increased	3/18 (16.7%)	3
Blood alkaline phosphatase increased	2/18 (11.1%)	2
Blood amylase decreased	1/18 (5.6%)	1
Blood bilirubin increased	1/18 (5.6%)	1
Blood calcium decreased	2/18 (11.1%)	2
Blood chloride decreased	1/18 (5.6%)	1
Blood cortisol decreased	1/18 (5.6%)	1
Blood creatinine decreased	1/18 (5.6%)	1
Blood creatinine increased	2/18 (11.1%)	2
Blood glucose increased	2/18 (11.1%)	2
Blood potassium increased	1/18 (5.6%)	1
Blood pressure orthostatic	1/18 (5.6%)	1
Blood sodium decreased	4/18 (22.2%)	4
Blood uric acid increased	1/18 (5.6%)	1
Carbon dioxide decreased	1/18 (5.6%)	1
International normalized ratio increased	3/18 (16.7%)	3
Weight decreased	2/18 (11.1%)	2
Metabolism and nutrition disorders
Anorexia	13/18 (72.2%)	13
Dehydration	7/18 (38.9%)	7
Hyperglycemia	1/18 (5.6%)	1
Hyperkalemia	1/18 (5.6%)	1
Hypoalbuminemia	1/18 (5.6%)	1
Hypocalcemia	2/18 (11.1%)	2
Hyponatremia	1/18 (5.6%)	1
Hypokalemia	3/18 (16.7%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	1/18 (5.6%)	1
Arthritis	1/18 (5.6%)	1
Back pain	5/18 (27.8%)	5
Joint swelling	2/18 (11.1%)	2
Muscle spasms	1/18 (5.6%)	1
Musculoskeletal pain	2/18 (11.1%)	2
Myalgia	1/18 (5.6%)	1
Neck pain	2/18 (11.1%)	2
Pain in extremity	1/18 (5.6%)	1
Pain in jaw	2/18 (11.1%)	2
Sensation of heaviness	1/18 (5.6%)	1
Shoulder pain	1/18 (5.6%)	1
Temporomandibular joint syndrome	1/18 (5.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Keratoacanthoma	1/18 (5.6%)	1
Nervous system disorders
Balance disorder	1/18 (5.6%)	1
Dizziness	3/18 (16.7%)	3
Dysgeusia	5/18 (27.8%)	5
Headache	5/18 (27.8%)	5
Hyperesthesia	1/18 (5.6%)	1
Hypoesthesia	4/18 (22.2%)	4
Migraine	1/18 (5.6%)	1
Psychiatric disorders
Abnormal dreams	1/18 (5.6%)	1
Anxiety	3/18 (16.7%)	3
Depression	3/18 (16.7%)	3
Insomnia	2/18 (11.1%)	2
Nightmare	1/18 (5.6%)	1
Renal and urinary disorders
Dysuria	2/18 (11.1%)	2
Hematuria	2/18 (11.1%)	2
Incontinence	1/18 (5.6%)	1
Micturition disorder	1/18 (5.6%)	1
Micturition urgency	1/18 (5.6%)	1
Nocturia	2/18 (11.1%)	2
Pollakiuria	1/18 (5.6%)	1
Proteinuria	2/18 (11.1%)	2
Renal failure	1/18 (5.6%)	1
Urinary incontinence	2/18 (11.1%)	2
Reproductive system and breast disorders
Breast mass	1/18 (5.6%)	1
Breast pain	1/18 (5.6%)	1
Testicular pain	1/18 (5.6%)	1
Vaginal discharge	1/18 (5.6%)	1
Vaginal hemorrhage	1/18 (5.6%)	1
Vulvovaginal burning sensation	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Choking	1/18 (5.6%)	1
Cough	8/18 (44.4%)	8
Dysphonia	3/18 (16.7%)	3
Dyspnea	6/18 (33.3%)	6
Hiccups	2/18 (11.1%)	2
Lung disorder	1/18 (5.6%)	1
Nasal congestion	3/18 (16.7%)	3
Oropharyngeal pain	2/18 (11.1%)	2
Productive cough	4/18 (22.2%)	4
Rhinalgia	1/18 (5.6%)	1
Sputum discolored	2/18 (11.1%)	2
Upper respiratory tract infection	1/18 (5.6%)	1
Wheezing	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Acne	1/18 (5.6%)	1
Alopecia	1/18 (5.6%)	1
Dry skin	2/18 (11.1%)	2
Erythema	3/18 (16.7%)	3
Heat rash	2/18 (11.1%)	2
Hyperhidrosis	5/18 (27.8%)	5
Night sweats	5/18 (27.8%)	5
Pain of skin	4/18 (22.2%)	4
Palmar-plantar erythrodysesthesia syndrome	4/18 (22.2%)	4
Photosensitivity reaction	1/18 (5.6%)	1
Pruritus	2/18 (11.1%)	2
Rash	5/18 (27.8%)	5
Rash macular	1/18 (5.6%)	1
Skin chapped	1/18 (5.6%)	1
Skin exfoliation	1/18 (5.6%)	1
Urticaria	1/18 (5.6%)	1
Vascular disorders
Hypotension	2/18 (11.1%)	2
Hot flush	9/18 (50%)	9
Hypertension	10/18 (55.6%)	10
Orthostatic hypotension	1/18 (5.6%)	1

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.