Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)

• Sponsor: Accelerated Community Oncology Research Network (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00452387
• Collaborator: Bayer (Industry)
• Enrollment: 22
• Locations: 10
• Duration (Months): 20.1
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if the combination of mitoxantrone, prednisone and sorafenib will improve the time to progression of advanced stage metastatic hormone-refractory prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Prostate Cancer	Drug: Mitoxantrone; Drug: Prednisone; Drug: Sorafenib	Phase 2

Detailed Description

The primary objective of this study is to test the hypothesis that the combination of Mitoxantrone, Prednisone and Sorafenib in taxane-refractory patients with metastatic hormone refractory prostate cancer (mHRPC) will result in an improvement of the median time to progression (TTP). Since the median (i.e 50% of patients) TTP for Mitoxantrone/Prednisone is 3 months, our hypothesis is that 70% will have not progressed at 3 months with this investigational combination. Progression will be assessed by radiologic imaging criteria.

The early stopping point is 21 subjects. If 10 or fewer subjects with tumor favorable response are observed when 21 subjects are accrued then the null hypothesis is accepted and the trial is terminated. If 16 or more subjects with tumor favorable response are observed when 21 subjects are accrued then the alternative hypothesis is accepted and the trial is terminated. The probability of early stopping under the null is 0.51, and under the alternative is 0.39. If the trial progresses until 42 subjects are evaluated and 24 or more subjects with favorable response are observed then the null hypothesis is rejected. This design minimizes the average sample number under the null, which is 31.2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jan 1, 2009

Outcome Measures

Primary Outcome Measures

1. Median Time to Progression (TTP) by Imaging [Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.]

   Time to progression is defined as the time from treatment start until objective tumor progression. The median time to progression is the parameter used to describe TTP.

Secondary Outcome Measures

1. Correlation of Biochemical Criteria (PSA, Prostate-specific Antigen) With Objective Imaging [PSA was evaluated on day 1 of every cycle (approximately every 3 weeks) during study treatment. Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.]

   The test of association assesses the null hypothesis that the frequency of PSA response is the same for patients with and without a favorable imaging response. PSA response required a 50% reduction of the baseline PSA result that was confirmed three weeks later. Favorable imaging response is defined as stable disease, partial response, or complete response per RECIST guidelines. The Fisher's exact test was used to test this hypothesis.

2. Quality of Life (QoL) [The Patient Care Monitor questionnaire was administered on day 1 of every cycle (approximately every 3 weeks) during study treatment.]

   The subject answers questions from the following 6 categories: general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation. Each question has a scale from 0 through 10, where 0 is not a problem and 10 is as bad as possible. The scores for the 6 categories are combined and normalized, and used to describe overall quality of life. Because normalized scores are created using a look-up index, there is no clearly defined maximum value. In practice, the maximum value for the combined scale is 73.5.

3. Median Overall Survival (OS) [Overall survival was measured from day 1 of treatment until the end of treatment and then every 3 months thereafter until death.]

   Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Voluntary written informed consent

• Histopathologic diagnosis of prostatic adenocarcinoma with evidence of progression despite adequate castration (testosterone < 50 ng/dL)

• Progressive disease after taxane-based chemotherapy (docetaxel or paclitaxel, single agent or combination regimens, weekly or every 21 day schedules)

• Patients who discontinued taxane- based chemotherapy because of toxicity will be eligible as long as there is evidence of progressive disease

• Minimum of 4 weeks period from last chemotherapy infusion to registration (this does not apply to steroid use which is permitted). Estramustine needs to be discontinued at least 6 weeks prior to first day of treatment on protocol

• A minimum of 4 weeks off bicalutamide, nilutamide, megestrol acetate ketoconazole, diethylstilbestrol (DES). Minimum of 2 weeks off flutamide

• Reductase inhibitors will be allowed if initiated at least 2 months prior to registration

• No concurrent investigational therapy

• Complementary and Alternative Medicine (CAM) products will be permitted as long as patients have been receiving them for at least 2 months. Initiation of new CAM products while on protocol will be discouraged.

• Ongoing androgen deprivation therapy (orchiectomy, gonadotropin-releasing hormone (GnRH) agonist or antagonist)

• Adequate bone marrow, liver and renal function as assessed by the following:

• Hemoglobin ≥ 9.0 g/dl

• Absolute neutrophil count (ANC) ≥ 1,500/mm3

• Platelet count ≥ 100,000/mm3

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT and AST ≤ 2.5 times the ULN ( ≤ 5 x ULN for patients with liver involvement)

• Creatinine ≤ 1.5 times the ULN

• International normalized ratio (INR) < 1.5 or a Prothrombin (PT)/Partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

• ECOG performance status ≤ 2

• Baseline left ventricular ejection fraction (LVEF) ≥ 50%

• Life expectancy ≥ 3 months

• Patients must agree to use adequate contraception prior to study entry, during the study and for at least three months after the last administration of sorafenib

Exclusion Criteria:

• More than one line of prior cytotoxic chemotherapy in the metastatic setting, previous adjuvant chemotherapy will be allowed

• No active malignancy other than prostate cancer (except non-melanoma skin cancer) within 5 years of enrollment

• Known brain metastases

• Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months

• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

• Uncontrolled hypertension

• Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2

• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months

• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug

• Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug

• Poorly controlled hyperglycemia

• Treatment with radiotherapy within 4 weeks or treatment with radiopharmaceuticals within past 8 weeks

• Patient has received other investigational drugs within 14 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study

• Serious non-healing wound or ulcer

• Evidence or history of bleeding diathesis or coagulopathy

• Use of St. John's Wort or rifampin

• Known or suspected allergy to sorafenib or any agent given in the course of this trial

• Any condition that impairs patient's ability to swallow whole pills

• Any malabsorption problem

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wilshire Oncology Medical Group, Inc.	La Verne	California	United States	91750
2	Peachtree Hematology Oncology Consultants	Atlanta	Georgia	United States	30309
3	Central Georgia Cancer Care	Macon	Georgia	United States	31201
4	Northwest Georgia Oncology Centers	Marietta	Georgia	United States	30060
5	Hematology Oncology Centers of the Northern Rockies, PC	Billings	Montana	United States	59101
6	Mid-Ohio Oncology/Hematology, Inc.	Columbus	Ohio	United States	43213
7	Lancaster Cancer Center	Lancaster	Pennsylvania	United States	17605
8	Pennsylvania Oncology Hematmology Associates	Philadelphia	Pennsylvania	United States	19106
9	The West Clinic	Memphis	Tennessee	United States	38120
10	Cancer Specialists of Tidewater	Chesapeake	Virginia	United States	23320

Sponsors and Collaborators

• Accelerated Community Oncology Research Network
• Bayer

Investigators

• Principal Investigator: Vasily Assikis, MD, Peachtree Hematology Oncology Consultants

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT00452387
• Other Study ID Numbers: ACORN AVAHRPC0607
• First Posted: Mar 27, 2007
• Last Update Posted: Sep 16, 2011
• Last Verified: Sep 1, 2011

• Keywords provided by Accelerated Community Oncology Research Network: Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Sorafenib; Mitoxantrone

Study Results

Participant Flow

Recruitment Details	10 community oncology research sites across the US within the ACORN network participated in this study. Enrollment started in May 2007 and was closed in July 2008 after the interim analysis was completed.
Pre-assignment Detail	Informed consent was obtained from all subjects. All subjects underwent a screening period that could last up to 4 weeks during which pre-study assessments were completed.

Arm/Group Title	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
Arm/Group Description	The treatment plan for all subjects was mitoxantrone 12 mg/m2 IV every 21 days; sorafenib 400 mg po bid daily; and prednisone 5 mg po bid daily.
Period Title: Overall Study
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
Arm/Group Description	The treatment plan for all subjects was mitoxantrone 12 mg/m2 IV every 21 days; sorafenib 400 mg po bid daily; and prednisone 5 mg po bid daily.
Overall Participants	22
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 36.4%
>=65 years	14 63.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67 (9)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	22 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 9.1%
White	20 90.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Median Time to Progression (TTP) by Imaging
Description	Time to progression is defined as the time from treatment start until objective tumor progression. The median time to progression is the parameter used to describe TTP.
Time Frame	Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.

Outcome Measure Data

Analysis Population Description

Survival analysis was performed for 22 patients. However, the upper 95% confidence interval for median TTP could not be calculated and so the number of patients analyzed and the upper 95% confidence interval for median TTP could not be entered into the system.

Arm/Group Title	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
Arm/Group Description	The treatment plan for all subjects was mitoxantrone 12 mg/m2 IV every 21 days; sorafenib 400 mg po bid daily; and prednisone 5 mg po bid daily.
Measure Participants	0

2. Secondary Outcome

Title	Correlation of Biochemical Criteria (PSA, Prostate-specific Antigen) With Objective Imaging
Description	The test of association assesses the null hypothesis that the frequency of PSA response is the same for patients with and without a favorable imaging response. PSA response required a 50% reduction of the baseline PSA result that was confirmed three weeks later. Favorable imaging response is defined as stable disease, partial response, or complete response per RECIST guidelines. The Fisher's exact test was used to test this hypothesis.
Time Frame	PSA was evaluated on day 1 of every cycle (approximately every 3 weeks) during study treatment. Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imaging Response (Favorable)	Imaging Response (Unfavorable)
Arm/Group Description
Measure Participants	9	13
PSA response (> 50% reduction)	3 13.6%	0 NaN
PSA response (< or = 50% reduction)	6 27.3%	13 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib, Imaging Response (Unfavorable)
	Comments	The test of association of PSA and imaging response tests the null hypothesis that the proportion of cases exhibiting PSA response is the same for patients with and without a favorable imaging response. A 2x2 table was constructed based on the number of the patients in imaging response (favorable and unfavorable) and PSA response (>50% reduction and <=50% reduction). The Fisher's exact test was used to test this hypothesis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Quality of Life (QoL)
Description	The subject answers questions from the following 6 categories: general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation. Each question has a scale from 0 through 10, where 0 is not a problem and 10 is as bad as possible. The scores for the 6 categories are combined and normalized, and used to describe overall quality of life. Because normalized scores are created using a look-up index, there is no clearly defined maximum value. In practice, the maximum value for the combined scale is 73.5.
Time Frame	The Patient Care Monitor questionnaire was administered on day 1 of every cycle (approximately every 3 weeks) during study treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
Arm/Group Description	The treatment plan for all subjects was mitoxantrone 12 mg/m2 IV every 21 days; sorafenib 400 mg po bid daily; and prednisone 5 mg po bid daily.
Measure Participants	22
Baseline	50.21
Cycle 1	49.71
Cycle 2	51.06
Cycle 3	51.20
Cycle 4	51.66
Cycle 5	51.22
Cycle 6	49.73
Cycle 7	49.50
Cycle 8	48.20
Cycle 9	54.34
Cycle 10	55.88
Cycle 11	54.95
Cycle 12	54.02
Cycle 13	54.65
End of Study (at treatment discontinuation)	45.13

4. Secondary Outcome

Title	Median Overall Survival (OS)
Description	Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS.
Time Frame	Overall survival was measured from day 1 of treatment until the end of treatment and then every 3 months thereafter until death.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
Arm/Group Description	The treatment plan for all subjects was mitoxantrone 12 mg/m2 IV every 21 days; sorafenib 400 mg po bid daily; and prednisone 5 mg po bid daily.
Measure Participants	22
Median (95% Confidence Interval) [Months]	12.32

Adverse Events

Time Frame	Adverse events were collected beginning on day 1 of study treatment until one month after the end of study treatment.
Adverse Event Reporting Description	Systematic Assessment - subjects were assessed for adverse events on day 1 of each cycle by either the research coordiantor, treating physician, or other appropriate sub-investigator.
Arm/Group Title	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
Arm/Group Description	The treatment plan for all subjects was mitoxantrone 12 mg/m2 IV every 21 days; sorafenib 400 mg po bid daily; and prednisone 5 mg po bid daily.
All Cause Mortality
	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
	Affected / at Risk (%)	# Events
Total	10/22 (45.5%)
Blood and lymphatic system disorders
Neutropenia	1/22 (4.5%)	1
Gastrointestinal disorders
Acute gastritis	1/22 (4.5%)	1
Nausea	1/22 (4.5%)	1
Pain - abdominal	2/22 (9.1%)	2
Vomiting	1/22 (4.5%)	1
Dysphagia	1/22 (4.5%)	1
General disorders
Death	1/22 (4.5%)	1
Necrosis	1/22 (4.5%)	1
Pain - chest	1/22 (4.5%)	1
Infections and infestations
Acute osteomylitis	1/22 (4.5%)	1
Esophageal candidiasis	1/22 (4.5%)	1
Metabolism and nutrition disorders
Dehydration	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis of mandible	1/22 (4.5%)	1
Pain - hip	1/22 (4.5%)	1
Pain - jaw	1/22 (4.5%)	1
Pain - shoulder	1/22 (4.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic small cell lung cancer	1/22 (4.5%)	1
Nervous system disorders
Lower extremities paraparesis	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Hand and foot syndrome	1/22 (4.5%)	1
Rash/desquamation	1/22 (4.5%)	1
Vascular disorders
Deep vein thrombosis of lower extremity	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment Group: Mitoxantrone, Prednisone, Plus Sorafenib
	Affected / at Risk (%)	# Events
Total	20/22 (90.9%)
Blood and lymphatic system disorders
Anemia	3/22 (13.6%)	5
Leukopenia	1/22 (4.5%)	2
Neutropenia	5/22 (22.7%)	5
Thrombocytopenia	1/22 (4.5%)	2
Eye disorders
Blurred vision	1/22 (4.5%)	1
Eye floaters	1/22 (4.5%)	1
Watery eyes	1/22 (4.5%)	1
Gastrointestinal disorders
Anal buccal tenderness	1/22 (4.5%)	1
Bloating	1/22 (4.5%)	1
Change in taste of food	1/22 (4.5%)	1
Constipation	1/22 (4.5%)	1
Diarrhea	8/22 (36.4%)	10
Dry heaves	1/22 (4.5%)	1
Dysphagia	1/22 (4.5%)	1
Flatulence	1/22 (4.5%)	1
Gastrointestinal - abdomen NOS (intermittent)	1/22 (4.5%)	1
Heartburn	2/22 (9.1%)	2
Hemoccult positive stools	1/22 (4.5%)	1
Melanotic stools	1/22 (4.5%)	1
Mouth sores	2/22 (9.1%)	2
Nausea	9/22 (40.9%)	12
Pain - abdomen	1/22 (4.5%)	1
Pain - esophagus	1/22 (4.5%)	2
Peridontal disease	1/22 (4.5%)	1
Sore mouth	1/22 (4.5%)	1
Stomatitis	2/22 (9.1%)	2
Vomiting	4/22 (18.2%)	7
General disorders
Ankle edema	1/22 (4.5%)	1
Bilateral lower extremity edema	1/22 (4.5%)	1
Fatigue	13/22 (59.1%)	14
Flu-like symptoms	2/22 (9.1%)	2
Mucositis	8/22 (36.4%)	8
Pain - chest	3/22 (13.6%)	3
Rigors without temperature	1/22 (4.5%)	1
Weakness	2/22 (9.1%)	2
Infections and infestations
Bronchitis	1/22 (4.5%)	1
Diverticulitis	1/22 (4.5%)	1
Herpes zoster	1/22 (4.5%)	1
Positive blood cultures	1/22 (4.5%)	1
Shingles	1/22 (4.5%)	1
Upper respiratory infection	1/22 (4.5%)	1
Urinary tract infection	2/22 (9.1%)	2
Injury, poisoning and procedural complications
T12 compression fracture	1/22 (4.5%)	1
Investigations
Cardiac catheter	1/22 (4.5%)	1
Decreased ejection fraction	1/22 (4.5%)	1
Elevated ALT	1/22 (4.5%)	1
Elevated AST	1/22 (4.5%)	1
Elevated blood pressure	1/22 (4.5%)	1
Elevated liver enzymes	1/22 (4.5%)	1
Fever	1/22 (4.5%)	1
Metabolism and nutrition disorders
Anorexia	6/22 (27.3%)	6
Dehydration	1/22 (4.5%)	1
Hypoalbuminemia	1/22 (4.5%)	1
Hypocalcemia	1/22 (4.5%)	1
Hypokalemia	2/22 (9.1%)	3
Hypomagnesemia	1/22 (4.5%)	2
Iron deficiency	1/22 (4.5%)	1
Weight gain	1/22 (4.5%)	1
Weight loss	7/22 (31.8%)	7
Musculoskeletal and connective tissue disorders
Cramping - bilateral feet	1/22 (4.5%)	1
Cramping - bilateral hands	1/22 (4.5%)	1
Pain - abdominal	1/22 (4.5%)	1
Pain - hip	4/22 (18.2%)	6
Pain - jaw	1/22 (4.5%)	1
Pain - lower back	2/22 (9.1%)	2
Pain - muscles	1/22 (4.5%)	1
Pain - right flank	1/22 (4.5%)	1
Pain - shoulder	1/22 (4.5%)	1
Pain - thighs	1/22 (4.5%)	1
Weakness - legs	2/22 (9.1%)	2
Nervous system disorders
Disequilibrium	1/22 (4.5%)	1
Dizziness	3/22 (13.6%)	3
Headache	3/22 (13.6%)	3
Neuropathy	1/22 (4.5%)	1
Neuropathy - peripheral	1/22 (4.5%)	1
Neuropathy - sensory	1/22 (4.5%)	1
Pain - sinus	1/22 (4.5%)	1
Psychiatric disorders
Depression	1/22 (4.5%)	1
Mental status change	1/22 (4.5%)	1
Renal and urinary disorders
Frequent urination	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/22 (4.5%)	1
Dyspnea	6/22 (27.3%)	10
Hoarseness	1/22 (4.5%)	1
Nasal congestion	1/22 (4.5%)	1
Pleural effusion	1/22 (4.5%)	2
Pulmonary edema	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Alopecia	4/22 (18.2%)	4
Dry skin	1/22 (4.5%)	1
Erythema	1/22 (4.5%)	1
Erythema - face	1/22 (4.5%)	1
Erythema - feet	1/22 (4.5%)	1
Hand and foot syndrome	1/22 (4.5%)	1
Nail discoloration	1/22 (4.5%)	1
Numbness in face	1/22 (4.5%)	1
Onycholysis right thumbnail	1/22 (4.5%)	1
Pruritis / itching scalp	1/22 (4.5%)	1
Rash	4/22 (18.2%)	4
Rash - back	1/22 (4.5%)	1
Rash - face	1/22 (4.5%)	1
Rash - generalized	1/22 (4.5%)	1
Rash - hand/foot/scalp	1/22 (4.5%)	1
Rash - mouth	1/22 (4.5%)	1
Rash - hand and foot	1/22 (4.5%)	3
Ruddy complexion	1/22 (4.5%)	1
Sensory neuropathy sensitivity - feet	1/22 (4.5%)	1
Skin irritation	1/22 (4.5%)	1
Tingling on scalp	1/22 (4.5%)	1
Surgical and medical procedures
Stent placement	1/22 (4.5%)	1
Vascular disorders
Hypertension	4/22 (18.2%)	5
Hypotension	2/22 (9.1%)	2

Limitations/Caveats

Early termination, according to the stopping rule included in the protocol, leading to a small number of subjects analyzed

More Information

Certain Agreements

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

Prior to publication or presentation of Sponsored Research results, Researcher agrees to provide Bayer with such presentation or manuscript at least 30 days prior to its submission for the sole purpose of allowing Bayer to redact confidential information and protect any existing or future patents. The Principal Investigator shall acknowledge Bayer contributions where appropriate.