Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL

• Sponsor: Kyowa Kirin Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00355472
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This is a Phase I label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell lymphoma (PTCL).

Condition or Disease	Intervention/Treatment	Phase
Adult T-Cell Leukemia and Lymphoma (ATL); Adult Peripheral T-Cell Lymphoma (PTCL)	Drug: KW-0761	Phase 1

Detailed Description

This is a Phase I open-label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL). This study is designed to evaluate safety, pharmacokinetics, immunogenicity and preliminary efficacy. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose (RPIID) have been established.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Dose Escalation Study of KW-0761 in Patients With Relapsed Adult T-Cell Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL)
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 KW-0761	Drug: KW-0761; IV administration at 4 escalating dose levels.

Outcome Measures

Primary Outcome Measures

1. Incidence of Dose-Limiting Toxicities (DLTs) [28 days]

   Subjects who were properly monitored for DLTs were to be analyzed to determine the number of subjects with a DLT by dose level.

2. Maximum Tolerated Dose (MTD) [28 days]

   The dose level at which Dose-Limiting Toxicity (DLT) was recognized was to be regarded as Maximum Tolerated Dose (MTD), and the dose level below MTD by one level was to be regarded as the recommended dose level (when MTD was not reached, 1.0 mg/kg was to be regarded as the recommended dose level) and 3 more subjects were to be newly added to the recommended dose level.

3. Pharmacokinetics-Plasma KW-0761 Concentrations [0-7 days post final dose]

   Plasma KW-0761 concentrations were to be summarized in tabular form with the descriptive statistics on a dose-by-dose basis. Individual and mean (+ standard deviation) plasma KW-0761 concentrations on an actual or logarithmic scale were to be plotted against the time of blood sampling.

4. Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (AUC0-7 Days) [0-7 days post final dose]

   The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.

5. Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (t1/2) [0 to 28 days post final dose and follow-up examinations (1 month and 2 months after the end of the post-dosing observation period).]

   The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.

Secondary Outcome Measures

1. Antitumor Effect [50 days]

   The antitumor response criteria (Complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) were created based on the criteria for non-Hodgkin's lymphoma and chronic lymphocytic leukemia provided in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as well as the criteria for non-Hodgkin's lymphoma by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG).

2. Time to Progression (TTP) [Baseline to response]

   TTP was defined as the period from the day starting the first KW-0761 dosing to the day of PD identification (or the day of death if the subject died before PD was documented). Subjects were to be censored at the time of starting post-treatment, if it was started before PD identification.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically confirmed diagnosis of a CCR4-positive ATL and PTCL that is any of the following:

1. ATL (Adult T-Cell Leukemia-Lymphoma)

• Seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody;

• Acute, Lymphoma, or Chronic phase with high-risk factors (within 14 days before the study entry);

1. PTCL (Peripheral T-Cell Lymphoma)

• Includes Mycosis Fungoides and Sezary Syndrome;

2: Relapsed to the latest standard chemotherapy;

3: Received at least one prior chemotherapy;

4: After 4 weeks from a prior therapy;

5: Have measurable disease;

6:Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1;

7: Male or female, at least 20 years and not older than 70 years of age;

8: Signed written informed consent;

9: Stay in hospital for 4 weeks;

10: HBs antigen: negative, HBV-DNA: below the limit of quantification (within 14 days before the study entry);

11: Adequate bone marrow, hepatic and cardiac function including the followings:

• Neutrophil count ≥ 1,500 /mm3,

• Platelets ≥ 75,000 /mm3,

• Hemoglobin ≥ 8.0 g/dL

• Serum creatinine ≤ 1.5 x ULN;

• Serum SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN (≤ 5.0 x ULN if considered due to disease involvement in liver);

• Serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if considered due to disease involvement in liver)

• Serum calcium ≤ 11.0 mg/dL

• PaO2 ≥ 65 mmHg or SaO2 ≥ 90%

• No clinically significant Electrocardiogram abnormality

• Left Ventricular Ejection Fraction ≥ 50% [by ECHO or MUGA]

Exclusion Criteria:

1. Co-existing active infection or any co-existing medical condition that may compromise the safety of patients during the study, affect the patient's ability to complete the study, or interfere with interpretation of study results;

2. Active tuberculosis;

3. Prior stem cell transplantation;

4. Myocardial infarction (within 12 months prior to the study entry);

5. Concurrent acute or chronic hepatitis, or cirrhosis;

6. Anti-HCV: positive, Anti-HIV: positive

7. Concurrent active malignant disease;

8. Known allergic reaction to antibody therapy;

9. Concomitant treatment with systemic steroids;

10. Prior and Concurrent psychiatric disorder including dementia, epilepsy or any other CNS diseases;

11. Evidence of CNS metastasis at baseline;

12. Prior and Concurrent spinal cord disease;

13. Radiation therapy for bulky mass disease at the time of study entry or considered to require radiation therapy during the study;

14. Female patients who are pregnant or breast feeding;

15. Female patients of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards;

16. Treatment with any other investigational agent within the 4 months prior to study entry;

17. For any reason is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tokyo		Japan

Sponsors and Collaborators

• Kyowa Kirin Co., Ltd.

Investigators

• Study Director: Study Director, Kyowa Kirin Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ishida T, Ueda R. CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci. 2006 Nov;97(11):1139-46. Epub 2006 Sep 5. Review. Erratum in: Cancer Sci. 2007 Jul;98(7):1137.
• Yano H, Ishida T, Inagaki A, Ishii T, Ding J, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R. Defucosylated anti CC chemokine receptor 4 monoclonal antibody combined with immunomodulatory cytokines: a novel immunotherapy for aggressive/refractory Mycosis fungoides and Sezary syndrome. Clin Cancer Res. 2007 Nov 1;13(21):6494-500.
• Yano H, Ishida T, Inagaki A, Ishii T, Kusumoto S, Komatsu H, Iida S, Utsunomiya A, Ueda R. Regulatory T-cell function of adult T-cell leukemia/lymphoma cells. Int J Cancer. 2007 May 1;120(9):2052-7.

• Responsible Party: Kyowa Kirin Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00355472
• Other Study ID Numbers: 0761-0501
• First Posted: Jul 24, 2006
• Last Update Posted: Oct 18, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Kyowa Kirin Co., Ltd.: Adult T-Cell Leukemia; ATL; Adult Peripheral T-Cell Lymphoma; PTCL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, T-Cell, Peripheral; Mogamulizumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 6 February 2007 through 22 October 2008

Arm/Group Title	KW-0761
Arm/Group Description	KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CC chemokine 4 receptor (CCR4) positive Adult T-Cell Leukemia-Lymphoma (ATL) or CCR4 positive Peripheral T-Cell Lymphoma (PTCL)
Period Title: Overall Study
STARTED	16
COMPLETED	15
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	KW-0761
Arm/Group Description	KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
Overall Participants	16
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	8 50%
Male	8 50%
Diagnosis (participants) [Number]
ATL	13 81.3%
PTCL	3 18.8%

Outcome Measures

1. Primary Outcome

Title	Incidence of Dose-Limiting Toxicities (DLTs)
Description	Subjects who were properly monitored for DLTs were to be analyzed to determine the number of subjects with a DLT by dose level.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KW-0761
Arm/Group Description	KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
Measure Participants	16
Number [participants]	1 6.3%

2. Primary Outcome

Title	Maximum Tolerated Dose (MTD)
Description	The dose level at which Dose-Limiting Toxicity (DLT) was recognized was to be regarded as Maximum Tolerated Dose (MTD), and the dose level below MTD by one level was to be regarded as the recommended dose level (when MTD was not reached, 1.0 mg/kg was to be regarded as the recommended dose level) and 3 more subjects were to be newly added to the recommended dose level.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KW-0761
Arm/Group Description	KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL
Measure Participants	16
Number [mg/kg]	1.0

3. Secondary Outcome

Title	Antitumor Effect
Description	The antitumor response criteria (Complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) were created based on the criteria for non-Hodgkin's lymphoma and chronic lymphocytic leukemia provided in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as well as the criteria for non-Hodgkin's lymphoma by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG).
Time Frame	50 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KW-0761 0.01mg	KW-0761 0.1mg	KW-0761 0.5mg	KW-0761 1.0mg
Arm/Group Description	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks
Measure Participants	3	4	3	6
Complete Response (CR)	0 0%	1 NaN	0 NaN	1 NaN
Uncertain Complete Response (CRu)	0 0%	0 NaN	0 NaN	0 NaN
Partial Response (PR)	1 6.3%	0 NaN	0 NaN	2 NaN
Stable Disease (SD)	1 6.3%	2 NaN	0 NaN	2 NaN
Progressive Disease (PD)	1 6.3%	1 NaN	3 NaN	1 NaN
Not Evaluable (NE)	0 0%	0 NaN	0 NaN	0 NaN

4. Primary Outcome

Title	Pharmacokinetics-Plasma KW-0761 Concentrations
Description	Plasma KW-0761 concentrations were to be summarized in tabular form with the descriptive statistics on a dose-by-dose basis. Individual and mean (+ standard deviation) plasma KW-0761 concentrations on an actual or logarithmic scale were to be plotted against the time of blood sampling.
Time Frame	0-7 days post final dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KW-0761 0.01mg	KW-0761 0.1mg	KW-0761 0.5mg	KW-0761 1.0mg
Arm/Group Description	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks
Measure Participants	3	4	3	6
Cmax	350.0 (47.8)	2806.7 (1664.5)	15181.2 (872.0)	40428.4 (5350.8)
Ctrough	158.2 (7.4)	1515.2 (1873.4)	6824.7 (872.9)	19516.8 (4264.7)

5. Primary Outcome

Title	Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (AUC0-7 Days)
Description	The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
Time Frame	0-7 days post final dose

Outcome Measure Data

Analysis Population Description

AUC0-7 days

Arm/Group Title	KW-0761 0.01mg	KW-0761 0.1mg	KW-0761 0.5mg	KW-0761 1.0mg
Arm/Group Description	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks
Measure Participants	3	4	3	6
Mean (Standard Deviation) [ng·h/mL]	36586 (2987)	327609 (322298)	1625609 (142277)	4190238 (544757)

6. Primary Outcome

Title	Pharmacokinetics-Pharmacokinetic Parameters of KW-0761 (t1/2)
Description	The pharmacokinetic parameters of the subjects were to be individually calculated, and their descriptive statistics were to be calculated on a dose-by-dose basis.
Time Frame	0 to 28 days post final dose and follow-up examinations (1 month and 2 months after the end of the post-dosing observation period).

Outcome Measure Data

Analysis Population Description

t1/2

Arm/Group Title	KW-0761 0.01mg	KW-0761 0.1mg	KW-0761 0.5mg	KW-0761 1.0mg
Arm/Group Description	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks	IV infusions of KW-0761 once/week for 4 weeks
Measure Participants	3	4	3	6
Mean (Standard Deviation) [hours]	179 (40)	201 (196)	332 (122)	462 (51)

7. Secondary Outcome

Title	Time to Progression (TTP)
Description	TTP was defined as the period from the day starting the first KW-0761 dosing to the day of PD identification (or the day of death if the subject died before PD was documented). Subjects were to be censored at the time of starting post-treatment, if it was started before PD identification.
Time Frame	Baseline to response

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KW-0761
Arm/Group Description	KW-0761 was administered 4 times at one-week intervals at a dose of 0.01, 0.1, 0.5 or 1.0 mg/kg in patients with CCR4 positive ATL or CCR4 positive PTCL.
Measure Participants	16
Median (Full Range) [days]	46.5

Adverse Events

Time Frame	28 days
Arm/Group Title	KW-0761 0.01mg		KW-0761 0.1mg		KW-0761 0.5mg		KW-0761 1.0mg
Arm/Group Description	IV infusions of KW-0761 once/week for 4 weeks		IV infusions of KW-0761 once/week for 4 weeks		IV infusions of KW-0761 once/week for 4 weeks		IV infusions of KW-0761 once/week for 4 weeks
All Cause Mortality
	KW-0761 0.01mg		KW-0761 0.1mg		KW-0761 0.5mg		KW-0761 1.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	KW-0761 0.01mg		KW-0761 0.1mg		KW-0761 0.5mg		KW-0761 1.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/4 (25%)		0/3 (0%)		1/6 (16.7%)
Infections and infestations
Herpes zoster	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	KW-0761 0.01mg		KW-0761 0.1mg		KW-0761 0.5mg		KW-0761 1.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		4/4 (100%)		3/3 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Lymph node pain	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Cardiac disorders
Tachycardia	0/3 (0%)	0	3/4 (75%)	3	0/3 (0%)	0	0/6 (0%)	0
Left ventricular dysfunction	2/3 (66.7%)	2	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Gastrointestinal disorders
Constipation	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0
Nausea	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0
General disorders
Chills	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2
Fatigue	1/3 (33.3%)	1	1/4 (25%)	1	1/3 (33.3%)	1	1/6 (16.7%)	1
Malaise	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0
Pyrexia	1/3 (33.3%)	1	0/4 (0%)	0	2/3 (66.7%)	2	1/6 (16.7%)	1
Infusion-related reaction	3/3 (100%)	3	3/4 (75%)	3	3/3 (100%)	3	4/6 (66.7%)	4
Immune system disorders
Cytokine release syndrome	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Infections and infestations
Nasopharyngitis	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0
Skin infection	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0
Investigations
Alanine aminotransferase increased	1/3 (33.3%)	1	1/4 (25%)	1	0/3 (0%)	0	2/6 (33.3%)	2
Aspartate aminotransferase increased	1/3 (33.3%)	1	1/4 (25%)	1	0/3 (0%)	0	2/6 (33.3%)	2
Blood albumin decreased	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	0/6 (0%)	0
Blood lactate dehydrogenase increased	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	2
Blood pressure increased	0/3 (0%)	0	1/4 (25%)	1	1/3 (33.3%)	1	1/6 (16.7%)	1
Blood sodium increased	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0
Electrocardiogram QT prolonged	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Blood urine present	1/3 (33.3%)	1	0/4 (0%)	0	0/3 (0%)	0	0/6 (0%)	0
Haemoglobin decreased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Heart rate increased	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Lymphocyte count decreased	2/3 (66.7%)	2	4/4 (100%)	4	3/3 (100%)	3	6/6 (100%)	6
Neutrophil count decreased	1/3 (33.3%)	1	2/4 (50%)	2	3/3 (100%)	3	4/6 (66.7%)	4
Neutrophil count increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Platelet count decreased	3/3 (100%)	3	2/4 (50%)	2	1/3 (33.3%)	1	3/6 (50%)	3
Protein total decreased	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	1/6 (16.7%)	1
Weight decreased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Weight increased	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0
White blood cell count decreased	1/3 (33.3%)	1	2/4 (50%)	2	3/3 (100%)	3	4/6 (66.7%)	4
White blood cell count increased	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Eosinophil percentage increased	1/3 (33.3%)	1	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Blood alkaline phosphatase increased	1/3 (33.3%)	1	2/4 (50%)	2	0/3 (0%)	0	1/6 (16.7%)	1
Platelet function test abnormal	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Metabolism and nutrition disorders
Anorexia	0/3 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1
Hypoalbuminaemia	1/3 (33.3%)	1	1/4 (25%)	1	0/3 (0%)	0	1/6 (16.7%)	1
Nervous system disorders
Dizziness	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Sensory disturbance	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/3 (0%)	0	0/4 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0
Pruritus	0/3 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	2/6 (33.3%)	2
Vascular disorders
Hypertension	1/3 (33.3%)	1	1/4 (25%)	1	0/3 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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