Randomized Phase 1/2 Open-Label Trial of PR104 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

• Sponsor: Proacta, Incorporated (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00862082
• Collaborator: (none)
• Enrollment: 14
• Locations: 17
• Arm: 1
• Duration (Months): 14
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The current understanding of PR104 justifies the evaluation of PR104 with sorafenib in patients with hepatocellular carcinoma. These include:

• Hypoxia. Hepatocellular Carcinoma (HCC) is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M. In addition, in preclinical models, sorafenib has been demonstrated to increase the degree of hypoxia in tumors following treatment.

• Non-overlapping toxicity. PR104 and sorafenib do not share major toxicities. It is anticipated that both drugs can be administered at their full single agent dose when used in combination.

• Aldo-keto reductase 1C3 (AKR1C3). HCC has been shown to express high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic HCC cells.

• Preclinical data. The use of sorafenib and PR104 alone and in combination in a hepatocellular carcinoma model demonstrates activity of PR104 as a single agent and increased activity when PR104 and sorafenib are used in combination.

The current study will provide an estimate of the activity of PR104 in subjects with HCC. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity in HCC to warrant a larger phase III registration study in this indication.

Primary objectives

• Phase I: Determine the maximum tolerated dose (MTD) of PR104 when used in combination with standard dose sorafenib

• Phase II: Estimate the response rate (RR) of PR104/sorafenib [Note: Phase II was never initiated]

Secondary objectives

• Evaluate survival

• Evaluate Progression Free Survival (PFS)

• Evaluate time to progression (TTP)

• Evaluate safety

• Evaluate the pharmacokinetics (PK) of sorafenib, PR104 and PR104 metabolites

• Collect diagnostic biopsy samples for the determination of aldo-keto reductase 1C3

• Collect plasma samples for assessment of potential biomarkers of tumor hypoxia

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: PR104 550 mg/m^2 + sorafenib; Drug: PR104 770 mg/m^2 + sorafenib	Phase 1/Phase 2

Detailed Description

A randomized phase I/II, multi-center, open-label, study with a single arm phase I portion to determine the appropriate dose of PR104 combined with sorafenib, followed by a phase II portion with randomization between sorafenib and sorafenib/PR104.

Following informed consent, subjects will undergo baseline evaluation with history, physical exams, blood work and disease assessment. Selected subjects will undergo PK assessment of sorafenib, PR104 and PR104 metabolites.

In the phase I portion of the study, the starting dose of PR104 will be 770 mg/mg2 in combination with standard dose sorafenib. PR104 will be administered on an every 4 week schedule with the dose of PR104 escalated in a standard phase I fashion (3 subjects per cohort, dose escalation between cohorts) in order to determine the MTD of PR104. Cohorts may be expanded up to 12 subjects to better define toxicity at a particular dose level. Following determination of the MTD of PR104, new subjects will be entered into the phase II portion of the study. [Note: the Phase II portion was never initiated]

In the phase II portion of the study, subjects will be randomized between sorafenib, 400 mg, by mouth (PO), twice a day (the approved dose and schedule) versus sorafenib with PR104 at the dose determined in the phase I portion of the study. PR104 will be administered every 4 weeks (one cycle). Subjects will be evaluated each week during cycle 1 and every two weeks thereafter. A disease assessment will be performed after every two cycles. Subjects with progression will be removed from study. Subjects with a response or stable disease may continue on study if this is considered beneficial by their physician.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase I/II, Multi-Center, Open-Label Trial of PR104 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: PR104 + Sorafenib PR104 will be administered IV once every four weeks, in addition to 400mg sorafenib PO twice daily

Drug: PR104 550 mg/m^2 + sorafenib; 550 mg/m^2 PR104 IV on day 1 of each 28 day cycle + 400 mg sorafenib PO twice daily. Number of Cycles: until progression or unacceptable toxicity develops.; Other Names: PR-104 Nexavar ; Drug: PR104 770 mg/m^2 + sorafenib; 770 mg/m^2 PR104 IV on day 1 of each 28 day cycle + 400 mg sorafenib PO twice daily. Number of Cycles: until progression or unacceptable toxicity develops.; Other Names: PR-104 Nexavar

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of PR104 When Used in Combination With Standard Dose Sorafenib in the Phase I Population [4 weeks (1 cycle)]

Secondary Outcome Measures

1. Safety and Tolerability: Serious Adverse Events [30 days following the last administration of study treatment]

   The number of participants with at least one Serious Adverse Event was measured.

2. Pharmacokinetics [Maximum Plasma Concentration (Cmax)] of PR104 and PR104 Metabolites in Cohort 1 (770 mg/m^2 Dose Group) [Day 1 of Cycles 1 and 2]

3. Pharmacokinetics [Half Life (T1/2)] of PR104 and PR104 Metabolites in Cohort 1 (770 mg/m^2 Dose Group) [Day 1 of Cycles 1 and 2]

4. Pharmacokinetics [Area Under the Curve(AUC)] of PR104 and PR104 Metabolites in Cohort 1 (770 mg/m^2 Dose Group) [Day 1 of Cycles 1 and 2]

5. Pharmacokinetics (Cmax) of PR104 and PR104 Metabolites in Cohort 2 (550 mg/m^2 Dose Group) [Day 1 of Cycles 1 and 2]

6. Pharmacokinetics (T1/2) of PR104 and PR104 Metabolites in Cohort 2 (550 mg/m^2 Dose Group) [Day 1 of Cycles 1 and 2]

7. Pharmacokinetics (AUC) of PR104 and PR104 Metabolites in Cohort 2 (550 mg/m^2 Dose Group) [Day 1 of Cycles 1 and 2]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Advanced-stage hepatocellular carcinoma considered non-operable that is suitable for treatment with sorafenib. Subjects who have demonstrated progression following initial surgical or locoregional therapy are eligible

• Confirmed hepatocellular carcinoma by pathological analysis (tissue aspirate or biopsy)

• No previous systemic therapy for hepatocellular carcinoma

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Child-Pugh liver function class A

• Life expectancy of 12 weeks or more

• Adequate hematologic function [Absolute neutrophil count (ANC) ≥ 1.5 x 10^{9/L; platelet count ≥100×10}9 per liter; hemoglobin ≥8.5 g per deciliter maintained in the absence of red blood cell transfusions; and prothrombin time international normalized ratio ≤1.7; or prothrombin time ≤2 seconds above control]

• Adequate hepatic function (albumin ≥2.8 g per deciliter; total bilirubin ≤2 mg per deciliter [51.3 μmol per liter]; and alanine aminotransferase and aspartate aminotransferase ≤5 times the upper limit of the normal range)

• Adequate renal function (serum creatinine ≤1.5 times the upper limit of the normal range or creatinine clearance ≥60 mL/min).

• At least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)

• Concomitant systemic antiviral therapy allowed

Exclusion Criteria:

• Previous molecularly targeted therapies or any other systemic treatment for hepatocellular carcinoma

• Active concomitant malignancy likely to effect any of the primary or secondary outcome measures in the current study

• Women who are pregnant, breast-feeding or planning to become pregnant during the study

• Men or women of reproductive-potential who are unwilling to use an effective method of contraception during the study and for 30 days following the last dose of study medication

• Evidence of a significant medical disorder or laboratory finding that, in the opinion of the Investigator, compromises the subject's safety during study participation such as: uncontrolled infection or infection requiring a concomitant parenteral antibiotic; uncontrolled diabetes; congestive heart failure; myocardial infarction within 6 months of study; chronic renal disease; or coagulopathy (excluding prophylactic anticoagulation)

• Active central nervous system metastatic disease requiring intervention

• Less than four weeks since major surgery

• Known Human Immunodeficiency Virus (HIV) positivity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85724
2	Moores UCSD Cancer Center	La Jolla	California	United States	92093
3	University of California, Irvine	Orange	California	United States	92868
4	Sharp Clinical Oncology Research	San Diego	California	United States	92123
5	Pacific Oncology/Hematology	San Francisco	California	United States	94115
6	Northwestern University	Chicago	Illinois	United States	60611
7	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
8	Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins	Baltimore	Maryland	United States	21231
9	Columbia University Medical Center	New York	New York	United States	10032
10	Prince of Wales Hospital	Shatin	New Territories	Hong Kong
11	Singapore General Hospital	Singapore		Singapore
12	Chang Gung Memorial Hospital	Kaohsiung		Taiwan
13	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan
14	Chi Mei Medical Center, Liouying	T'ai-nan		Taiwan
15	China Medical University Hospital	Taichung City		Taiwan
16	Cathay General Hospital	Taipei City		Taiwan	10630
17	National Taiwan University Hospital	Taipei		Taiwan

Sponsors and Collaborators

• Proacta, Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Proacta, Incorporated
• ClinicalTrials.gov Identifier: NCT00862082
• Other Study ID Numbers: PR104-2002; NCT00838604
• First Posted: Mar 16, 2009
• Last Update Posted: Aug 23, 2013
• Last Verified: Jul 1, 2013

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Sorafenib; Nitrogen Mustard Compounds

Study Results

Participant Flow

Arm/Group Title	PR104 550 mg/m^2 + Sorafenib	PR104 770 mg/m^2 + Sorafenib
Arm/Group Description	550 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)	770 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)
Period Title: Overall Study
STARTED	8	6
COMPLETED	3	5
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	PR104 550 mg/m^2 + Sorafenib	PR104 770 mg/m^2 + Sorafenib	Total
Arm/Group Description	550 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)	770 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)	Total of all reporting groups
Overall Participants	8	6	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 87.5%	5 83.3%	12 85.7%
>=65 years	1 12.5%	1 16.7%	2 14.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (13)	59 (13)	58 (13)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	0 0%	3 21.4%
Male	5 62.5%	6 100%	11 78.6%
Region of Enrollment (participants) [Number]
United States	2 25%	1 16.7%	3 21.4%
Taiwan	5 62.5%	2 33.3%	7 50%
Hong Kong	1 12.5%	3 50%	4 28.6%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of PR104 When Used in Combination With Standard Dose Sorafenib in the Phase I Population
Time Frame	4 weeks (1 cycle)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohorts 1 and 2
Arm/Group Description	770 and 550 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)
Measure Participants	14
Number [mg/m2]	NA

2. Secondary Outcome

Title	Safety and Tolerability: Serious Adverse Events
Description	The number of participants with at least one Serious Adverse Event was measured.
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	770 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)	550 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)
Measure Participants	6	8
Number [participants]	2 25%	5 83.3%

3. Secondary Outcome

Title	Pharmacokinetics [Maximum Plasma Concentration (Cmax)] of PR104 and PR104 Metabolites in Cohort 1 (770 mg/m^2 Dose Group)
Time Frame	Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Participation in pharmacokinetic (PK) sampling was optional to subjects, therefore not all subjects in the study were analyzed.

Arm/Group Title	PR104	PR104A	PR104G	PR104S1	PR104H	PR104M
Arm/Group Description	major plasma metabolite	major plasma metabolite	semi-mustard metabolite	activated reduced metabolites	activated reduced metabolites
Measure Participants	2	2	2	2	2	2
Cmax Cycle 1	7.1 (3.2)	7.6 (1.9)	9.6 (2.3)	0.17 (0.15)	0.21 (0.11)	0.04 (0.02)
Cmax Cycle 2	6.0 (3.3)	7.6 (1.0)	10.4 (2.2)	0.18 (0.07)	0.20 (0.05)	0.04 (0.02)

4. Secondary Outcome

Title	Pharmacokinetics [Half Life (T1/2)] of PR104 and PR104 Metabolites in Cohort 1 (770 mg/m^2 Dose Group)
Time Frame	Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Participation in PK sampling was optional to subjects, therefore not all subjects in the study were analyzed.

Arm/Group Title	PR104	PR104A	PR104G	PR104S1	PR104H	PR104M
Arm/Group Description	major plasma metabolite	major plasma metabolite	semi-mustard metabolite	activated reduced metabolites	activated reduced metabolites
Measure Participants	2	2	2	2	2	2
T1/2 Cycle 1	0.15 (0.10)	0.75 (0.35)	0.62 (0.08)	0.87 (0.11)	1.37 (0.18)	3.57 (0.82)
T1/2 Cycle 2	0.17 (0.11)	0.85 (0.20)	0.67 (0.17)	0.79 (0.14)	1.05 (0.35)	02.93 (2.48)

5. Secondary Outcome

Title	Pharmacokinetics [Area Under the Curve(AUC)] of PR104 and PR104 Metabolites in Cohort 1 (770 mg/m^2 Dose Group)
Time Frame	Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Participation in PK sampling was optional to subjects, therefore not all subjects in the study were analyzed.

Arm/Group Title	PR104	PR104A	PR104G	PR104S1	PR104H	PR104M
Arm/Group Description	major plasma metabolite	major plasma metabolite	semi-mustard metabolite	activated reduced metabolites	activated reduced metabolites
Measure Participants	2	2	2	2	2	2
AUC Cycle 1	5.1 (3.2)	11.0 (4.4)	12.3 (1.3)	0.26 (0.23)	0.47 (0.27)	0.22 (0.09)
AUC Cycle 2	4.3 (2.9)	10.6 (0.1)	15.8 (2.9)	0.28 (0.10)	0.42 (0.04)	0.19 (0.17)

6. Secondary Outcome

Title	Pharmacokinetics (Cmax) of PR104 and PR104 Metabolites in Cohort 2 (550 mg/m^2 Dose Group)
Time Frame	Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Participation in PK sampling was optional to subjects, therefore not all subjects in the study were analyzed.

Arm/Group Title	PR104	PR104A	PR104G	PR104S1	PR104H	PR104M
Arm/Group Description	major plasma metabolite	major plasma metabolite	semi-mustard metabolite	activated reduced metabolites	activated reduced metabolites
Measure Participants	5	5	1	5	5	5
Cmax Cycle 1	3.2 (1.1)	15.8 (8.9)	4.9 (NA)	0.21 (0.18)	0.72 (0.80)	0.12 (0.12)
Cmax Cycle 2	4.3 (0.7)	14.6 (10.4)	5.8 (NA)	0.17 (0.17)	0.69 (0.78)	0.16 (0.13)

7. Secondary Outcome

Title	Pharmacokinetics (T1/2) of PR104 and PR104 Metabolites in Cohort 2 (550 mg/m^2 Dose Group)
Time Frame	Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Participation in PK sampling was optional to subjects, therefore not all subjects in the study were analyzed.

Arm/Group Title	PR104	PR104A	PR104G	PR104S1	PR104H	PR104M
Arm/Group Description	major plasma metabolite	major plasma metabolite	semi-mustard metabolite	activated reduced metabolites	activated reduced metabolites
Measure Participants	5	5	1	5	5	5
T1/2 Cycle 1	0.10 (0.01)	0.68 (0.04)	0.53 (NA)	0.69 (0.20)	0.84 (0.34)	1.02 (0.42)
T1/2 Cycle 2	0.09 (0.01)	0.79 (0.23)	0.50 (NA)	0.90 (0.44)	0.91 (0.25)	0.99 (0.52)

8. Secondary Outcome

Title	Pharmacokinetics (AUC) of PR104 and PR104 Metabolites in Cohort 2 (550 mg/m^2 Dose Group)
Time Frame	Day 1 of Cycles 1 and 2

Outcome Measure Data

Analysis Population Description

Participation in PK sampling was optional to subjects, therefore not all subjects in the study were analyzed.

Arm/Group Title	PR104	PR104A	PR104G	PR104S1	PR104H	PR104M
Arm/Group Description	major plasma metabolite	major plasma metabolite	semi-mustard metabolite	activated reduced metabolites	activated reduced metabolites
Measure Participants	5	5	1	5	5	5
AUC Cycle 1	2.4 (0.8)	19.7 (9.7)	6.4 (NA)	0.30 (0.23)	0.81 (0.71)	0.18 (0.13)
AUC Cycle 2	3.3 (0.6)	22.7 (18.2)	7.6 (NA)	0.31 (0.21)	1.07 (1.02)	0.25 (0.18)

Adverse Events

Arm/Group Title	PR104 550 mg/m^2 + Sorafenib		PR104 770 mg/m^2 + Sorafenib
Arm/Group Description	550 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)		770 mg/m^2 PR104 administered IV every 4 weeks + Standard dose sorafenib (400 mg PO twice daily)
All Cause Mortality
	PR104 550 mg/m^2 + Sorafenib		PR104 770 mg/m^2 + Sorafenib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PR104 550 mg/m^2 + Sorafenib		PR104 770 mg/m^2 + Sorafenib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)		2/6 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	1/8 (12.5%)	1	0/6 (0%)	0
Gastrointestinal disorders
Abdominal Pain	2/8 (25%)	3	0/6 (0%)	0
General disorders
Decrease in general condition	1/8 (12.5%)	1	0/6 (0%)	0
Fatigue	0/8 (0%)	0	1/6 (16.7%)	1
Fever in absence of neutropenia	2/8 (25%)	2	0/6 (0%)	0
Infections and infestations
Cellulitis	1/8 (12.5%)	1	0/6 (0%)	0
Sepsis	0/8 (0%)	0	1/6 (16.7%)	1
Investigations
Thrombocytopenia	1/8 (12.5%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	PR104 550 mg/m^2 + Sorafenib		PR104 770 mg/m^2 + Sorafenib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Leukopenia	7/8 (87.5%)		4/6 (66.7%)
Anemia	4/8 (50%)		5/6 (83.3%)
Neutropenia	6/8 (75%)		3/6 (50%)
Thrombocytopenia	3/8 (37.5%)		5/6 (83.3%)
Febrile neutropenia	0/8 (0%)		1/6 (16.7%)
Gastrointestinal disorders
Abdominal pain	3/8 (37.5%)		2/6 (33.3%)
Diarrhea	3/8 (37.5%)		1/6 (16.7%)
Abdominal distension	1/8 (12.5%)		1/6 (16.7%)
Ascites	1/8 (12.5%)		1/6 (16.7%)
Constipation	1/8 (12.5%)		1/6 (16.7%)
Gingival bleeding	0/8 (0%)		1/6 (16.7%)
Vomiting	1/8 (12.5%)		0/6 (0%)
General disorders
Fatigue	3/8 (37.5%)		3/6 (50%)
Induration	1/8 (12.5%)		0/6 (0%)
Mucosal inflammation	0/8 (0%)		1/6 (16.7%)
Oedema peripheral	1/8 (12.5%)		0/6 (0%)
Pyrexia	0/8 (0%)		1/6 (16.7%)
Hepatobiliary disorders
Hyperbilirubinemia	3/8 (37.5%)		1/6 (16.7%)
Jaundice	1/8 (12.5%)		0/6 (0%)
Infections and infestations
Upper respiratory tract infection	1/8 (12.5%)		1/6 (16.7%)
Cellulitis	0/8 (0%)		1/6 (16.7%)
Urinary tract infection	1/8 (12.5%)		0/6 (0%)
Investigations
Aspartate aminotransferase increased	6/8 (75%)		3/6 (50%)
Alanine aminotransferase increased	4/8 (50%)		2/6 (33.3%)
Blood alkaline phosphatase increased	3/8 (37.5%)		1/6 (16.7%)
International normalised ratio increased	1/8 (12.5%)		0/6 (0%)
Weight decreased	1/8 (12.5%)		0/6 (0%)
Metabolism and nutrition disorders
Hypoalbuminemia	4/8 (50%)		3/6 (50%)
Anorexia	3/8 (37.5%)		2/6 (33.3%)
Hyperglycemia	1/8 (12.5%)		3/6 (50%)
Hyponatremia	1/8 (12.5%)		3/6 (50%)
Hypocalcemia	1/8 (12.5%)		1/6 (16.7%)
Hypokalemia	1/8 (12.5%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/8 (0%)		1/6 (16.7%)
Nervous system disorders
Coordination abnormal	1/8 (12.5%)		0/6 (0%)
Psychiatric disorders
Insomnia	1/8 (12.5%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		0/6 (0%)
Dyspnea	0/8 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	1/8 (12.5%)		2/6 (33.3%)
Leukocytoclastic vasulitis	1/8 (12.5%)		0/6 (0%)
Pruritis	1/8 (12.5%)		0/6 (0%)
Rash	1/8 (12.5%)		0/6 (0%)
Urticaria	0/8 (0%)		1/6 (16.7%)
Vascular disorders
Hypertension	1/8 (12.5%)		0/6 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed. Phase II part of study never initiated.

More Information

Certain Agreements

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

Single site data may be published/presented prior to the publication of multi-center data from overall study if agreed to by the sponsor in writing, or 12 months have elapsed following termination or completion of the study, whichever comes first.