Safety Study Using Weekly Infusions of BB-10901 in Patients With Small Cell Lung Cancer

• Sponsor: ImmunoGen, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00065429
• Collaborator: (none)
• Enrollment: 64
• Locations: 11
• Arms: 7
• Duration (Months): 68
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study was a Phase I/II trial primarily focused on efficacy of BB-10901 in relapsed small cell lung cancer and other solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: BB-10901	Phase 1/Phase 2

Detailed Description

The Phase II efficacy expansion was restricted to SCLC patients with relapsed disease and the MTD was determined by the Phase I portion of the trial (60mg/m2).

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open-Label, Dose Escalation Study of Weekly Dosing With BB-10901, Followed by a Phase II Efficacy Expansion
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BB-10901, 5mg/m2 - Phase I	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.
Experimental: BB-10901, 10 mg/m2 - Phase I	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.
Experimental: BB-10901, 20 mg/m2 - Phase I	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.
Experimental: BB-10901, 40 mg/m2 - Phase I	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.
Experimental: BB-10901, 60 mg/m2 - Phase I & Phase II Phase I and Phase II were consecutive and sequential. Different patients received the 60mg/m2 dose in Phase I and in Phase II.	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.
Experimental: BB-10901, 67.5 mg/m2 - Phase I	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.
Experimental: BB-10901, 75 mg/m2 - Phase I	Drug: BB-10901; I.V. Infusion - See "Arms" for dosage - Once/Week for three weeks - Until Progression of disease.

Outcome Measures

Primary Outcome Measures

1. Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) [every 6 weeks]

   Dose limiting toxicities graded according to common terminology criteria for advers events, version 2.0 and defined as AEs (probably/definitely related to study drug) meeting the NCI CTC criteria, assessed on the basis of the first cycle of therapy (4 weeks of weekly dosing/2 week fu): Hematologic Tox (Grade 4 neutropenia ≥ 5 days, Grade 4 thrombocytopenia, neutropenic infection); Non-Hem Toxicity: (Any grade 3 or 4 non-hematologic toxicity, excluding nausea, vomiting, diarrhea and alopecia); Toxicity present at Screening (concurrent conditions), an increase in severity of 2 or more grades.

2. Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] [6 weeks]

   Response was evaluated by RESIST and Investigator assessment at baseline and every 6 weeks. CR: all target lesions disappear with no clinical or radiographic evidence of disease progression in 2 observations. PR: At least 30% decrease in sum of the longest diameters of target lesions shown in 2 observations. SD: does not qalify for PR or PD based on 2 observations. PD: Either a) the appearance of one or more new lesions, or b) at least a 20% increase in the sum of longest diameters of target lesions

Eligibility Criteria

Criteria

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

Inclusion:

• Histologically or Cytologically proven SCLC, CD 56+ small cell carcinoma of unknown origin, or CD56+ non-pulmonary small cell carcinoma

• Relapsed disease; defined as patients with an initial response (partial or complete) to first-line therapy, then relapse more than 3 months after completion of last chemotherapy.

• Patients must have received no more than 3 prior chemotherapy regimen.

• Patients must have measurable disease defined as: Lesions that can be measured in at least one dimension according to RECIST

• Predicted survival of 3 months or more

• Zubrod performance status 0-2

• Patients must not have received chemotherapy or radiation therapy within 4 weeks of study entry, nor have planned surgery.

• Absolute neutrophils greater than or equal to 1.5 x 10^{9/l, hemoglobin greater than or equal to 9g/dl and platelets greater than or equal to 100 x 10}9/l.

• Creatinine less than or equal to 1.5 times the upper limit of normal

• AST/ALT less than or equal to 3 times the upper limit of normal without liver metastases; less than or equal to 5 times the upper limit of normal with liver metastases and bilirubin less than or equal to 1.5 times the upper limit of normal.

• Patients must have normal thyroid function (patients receiving thyroxin replacement therapy who are biochemically euthyroid may be enrolled).

• Women of childbearing potential must provide a negative pregnancy test at screening and use adequate contraception in the opinion of the investigator, for the duration of study.

• Patients must be capable of understanding the nature of the trial and must give written witnessed informed consent prior to any screening procedure.

Exclusion:

• Significant residual neurological or cardiac toxicity (grade 3 or 4) following previous chemotherapy

• Patients who are concurrently receiving other anti-neoplastic treatment (chemotherapy, radiotherapy, or immunotherapy including steroid therapy).

• Myocardial infarction within 6 months of study entry, unstable angina pectoris, uncontrolled congestive heart failure, uncontrolled arrythmia, severe aortic stenosis, a history of multiple sclerosis, or other demyelinating disease, Eaton-Lambert Syndrome, history of hemorrhagic stroke, any CNS injury with residual neurologic deficit, ischaemic stroke within the last 6 months, current known herpes zoster (shingles), or cytomegalovirus infection, or a history of recurrent infections with these viruses, chronic alcoholism, serious concomitant infection, or any other concomitant illness considered significant enough to interfere with the study outcome.

• Other investigational agents must not be taken during the study or within 4 weeks of study entry.

• Previous monoclonal antibody therapy

• Patients must not have known central nervous system metastases

• Previous malignancy with < 5 year disease free interval from the last therapeutic intervention, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.

• Patient unwilling or unable to tolerate and comply with the requirements of the study.

• Pregnant or lactating females.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
2	Cancer Center of Florida	Ocoee	Florida	United States	34761
3	Baystate Medical Center	Springfield	Massachusetts	United States	01107
4	New York Oncology Hematology	Albany	New York	United States	12208
5	The Ohio State University	Colombus	Ohio	United States	43221
6	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
7	Cancer Centers of the Carolinas	Greenville	South Carolina	United States	29605
8	MD Anderson Cancer Center	Houston	Texas	United States	77030-7095
9	Tyler Cancer Center	Tyler	Texas	United States	75702
10	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
11	Northwest Cancer Specialists	Vancouver	Washington	United States	98684

Sponsors and Collaborators

• ImmunoGen, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ImmunoGen, Inc.
• ClinicalTrials.gov Identifier: NCT00065429
• Other Study ID Numbers: C10/IVB/001; NCT00074256
• First Posted: Jul 24, 2003
• Last Update Posted: Jul 18, 2012
• Last Verified: Jul 1, 2012

• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Lorvotuzumab mertansine

Study Results

Participant Flow

Recruitment Details	In Phase I, 32 patients were treated with doses ranging from 5 mg/m2/week to 75 mg/m2/week, with 9 patients treated at the MTD dose of 60 mg/m2/week. In Phase II, 32 advanced cancer patients were treated with BB-10901 at a dose of 60 mg/m2/week. (Total N=64)
Pre-assignment Detail	This study was an open-label study. All patients that consented to the trial and met inclusion/exclusion criteria were enrolled.

Arm/Group Title	IMGN 5 mg/m2	IMGN 10 mg/m2	IMGN 20 mg/m2	IMGN 40 mg/m2	IMGN 60 mg/m2	IMGN 67.5 mg/m2	IMGN 75 mg/m2
Arm/Group Description	Arm 1, Phase 1	Arm 2, Phase 1	Arm 3, Phase 1	Arm 4, Phase 1	Arm 5, Phase 1 and 2	Arm 6, Phase 1	Arm 7, Phase 1
Period Title: Phase I - May 2001 - Oct 2002
STARTED	4	3	4	4	9	4	4
COMPLETED	3	3	3	3	8	2	2
NOT COMPLETED	1	0	1	1	1	2	2
Period Title: Phase I - May 2001 - Oct 2002
STARTED	0	0	0	0	32	0	0
COMPLETED	0	0	0	0	26	0	0
NOT COMPLETED	0	0	0	0	6	0	0

Baseline Characteristics

Arm/Group Title	IMGN 5 mg/m2	IMGN 10 mg/m2	IMGN 20 mg/m2	IMGN 40 mg/m2	IMGN 60 mg/m2	IMGN 67.5 mg/m2	IMGN 75 mg/m2	Total
Arm/Group Description	Arm 1, Phase 1	Arm 2, Phase 1	Arm 3, Phase 1	Arm 4, Phase 1	Arm 5, Phase 1 and 2	Arm 6, Phase 1	Arm 7, Phase 1	Total of all reporting groups
Overall Participants	4	3	4	4	41	4	4	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (10.86)	59.0 (13.08)	60.0 (12.65)	59.8 (9.07)	61.2 (10.1)	59.5 (4.8)	54.5 (9.5)	62.67 (10.01)
Age, Customized (participants) [Number]
>=18 years	4 100%	3 100%	4 100%	4 100%	41 100%	4 100%	4 100%	64 100%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	2 50%	1 25%	14 34.1%	1 25%	4 100%	23 35.9%
Male	4 100%	2 66.7%	2 50%	3 75%	27 65.9%	3 75%	0 0%	41 64.1%
Region of Enrollment (participants) [Number]
United States	4 100%	3 100%	4 100%	4 100%	41 100%	4 100%	4 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I)
Description	Dose limiting toxicities graded according to common terminology criteria for advers events, version 2.0 and defined as AEs (probably/definitely related to study drug) meeting the NCI CTC criteria, assessed on the basis of the first cycle of therapy (4 weeks of weekly dosing/2 week fu): Hematologic Tox (Grade 4 neutropenia ≥ 5 days, Grade 4 thrombocytopenia, neutropenic infection); Non-Hem Toxicity: (Any grade 3 or 4 non-hematologic toxicity, excluding nausea, vomiting, diarrhea and alopecia); Toxicity present at Screening (concurrent conditions), an increase in severity of 2 or more grades.
Time Frame	every 6 weeks

Outcome Measure Data

Analysis Population Description

All Phase I enrolled patients who received study drug were analyzed for DLTs.

Arm/Group Title	Phase I
Arm/Group Description	The study had a conventional open-label cytotoxic study design to determine the safety, tolerability and MTD, preliminary efficacy signal and PK. Once the MTD was found in Phase I, the study would continue to a Phase II expansion at the MTD and the MTD-1 dose levels determined in Phase I. Infusions given at 1-week intervals were expected to provide intermittent exposure with no accumulation of BB-10901. The maximum duration of treatment at each dose level was 4 cycles of treatment; patients with evidence of response were eligible to continue for up to 6 cycles of treatment. Dose levels planned were 5, 10, 20, 40, 60 and 90 mg/m2/week. Three patients were to be enrolled per dose level with dose escalation when 1 of 3 patients completed 1 cycle and 2 patients had received at least 2 weekly infusions and were eligible for their third infusion, all without DLT. Once the MTD had been defined, 3 more patients were planned for enrollment at the MTD and 3 patients at the MTD-1 level.
Measure Participants	32
Non-infective meningitis	3 (0) 75%
Hyperesthesia Grade 4	1 25%
Peripheral sensory neuropathy Grade 3	1 25%
Fatigue Grade 3	1 25%
Headache Grade 3	1 25%

2. Primary Outcome

Title	Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II]
Description	Response was evaluated by RESIST and Investigator assessment at baseline and every 6 weeks. CR: all target lesions disappear with no clinical or radiographic evidence of disease progression in 2 observations. PR: At least 30% decrease in sum of the longest diameters of target lesions shown in 2 observations. SD: does not qalify for PR or PD based on 2 observations. PD: Either a) the appearance of one or more new lesions, or b) at least a 20% increase in the sum of longest diameters of target lesions
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

All patients with a baseline and follow up imaging scan were evaluated. Data represents information following the first cycle of treatment.

Arm/Group Title	Phase I	Phase II
Arm/Group Description	The study had a conventional open-label cytotoxic study design to determine the safety, tolerability and MTD, preliminary efficacy signal and PK. Once the MTD was found in Phase I, the study would continue to a Phase II expansion at the MTD and the MTD-1 dose levels determined in Phase I. Infusions given at 1-week intervals were expected to provide intermittent exposure with no accumulation of BB-10901. The maximum duration of treatment at each dose level was 4 cycles of treatment; patients with evidence of response were eligible to continue for up to 6 cycles of treatment. Dose levels planned were 5, 10, 20, 40, 60 and 90 mg/m2/week. Three patients were to be enrolled per dose level with dose escalation when 1 of 3 patients completed 1 cycle and 2 patients had received at least 2 weekly infusions and were eligible for their third infusion, all without DLT. Once the MTD had been defined, 3 more patients were planned for enrollment at the MTD and 3 patients at the MTD-1 level.	For Phase II, the planned design was to use a Gehan's two-stage design [4], with a total of 14 patients assigned to each of 2 dose levels. The dose levels to be tested were to be selected after review of the Phase I data and, assuming evidence of efficacy was seen in that phase, were likely to be the MTD and MTD-1.
Measure Participants	29	29
Complete Response (CR) or Partial Response (PR)	0 0%	2 66.7%
Stable Disease	10 250%	10 333.3%
Progressive Disease (PD)	16 400%	17 566.7%
Unknown	3 75%	0 0%

Adverse Events

Time Frame	From 29 May, 2001 to 16 Oct, 2008
Arm/Group Title	IMGN 5 mg/m2		IMGN 10 mg/m2		IMGN 20 mg/m2		IMGN 40 mg/m2		IMGN 60 mg/m2		IMGN 67.5 mg/m2		IMGN 75 mg/m2
Arm/Group Description	Arm 1, Phase 1		Arm 2, Phase 1		Arm 3, Phase 1		Arm 4, Phase 1		Arm 5, Phase 1 and 2		Arm 6, Phase 1		Arm 7, Phase 1
All Cause Mortality
	IMGN 5 mg/m2		IMGN 10 mg/m2		IMGN 20 mg/m2		IMGN 40 mg/m2		IMGN 60 mg/m2		IMGN 67.5 mg/m2		IMGN 75 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	IMGN 5 mg/m2		IMGN 10 mg/m2		IMGN 20 mg/m2		IMGN 40 mg/m2		IMGN 60 mg/m2		IMGN 67.5 mg/m2		IMGN 75 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/3 (0%)		0/4 (0%)		1/4 (25%)		5/41 (12.2%)		1/4 (25%)		0/4 (0%)
Blood and lymphatic system disorders
Blood and Lymphatic	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	3	0/4 (0%)	0	0/4 (0%)	0
Cardiac disorders
Cardiac	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/41 (4.9%)	2	0/4 (0%)	0	0/4 (0%)	0
Endocrine disorders
Endocrine	1/4 (25%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	1	0/4 (0%)	0	0/4 (0%)	0
Gastrointestinal disorders
Gastrointestinal	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	4/41 (9.8%)	7	1/4 (25%)	1	0/4 (0%)	0
General disorders
General Disorders	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/41 (4.9%)	2	0/4 (0%)	0	0/4 (0%)	0
Metabolism and nutrition disorders
Metabolism and Nutritional Disorders	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	1	0/4 (0%)	0	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/41 (4.9%)	2	0/4 (0%)	0	0/4 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm	1/4 (25%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	3/41 (7.3%)	3	0/4 (0%)	0	0/4 (0%)	0
Nervous system disorders
Nervous System Disorders	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	4/41 (9.8%)	5	0/4 (0%)	0	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	2/41 (4.9%)	2	0/4 (0%)	0	0/4 (0%)	0
Surgical and medical procedures
Surgical and Medical Procedures	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	1	0/4 (0%)	0	0/4 (0%)	0
Vascular disorders
Vascular Disorders	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	1	0/4 (0%)	0	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	IMGN 5 mg/m2		IMGN 10 mg/m2		IMGN 20 mg/m2		IMGN 40 mg/m2		IMGN 60 mg/m2		IMGN 67.5 mg/m2		IMGN 75 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/3 (100%)		3/4 (75%)		4/4 (100%)		41/41 (100%)		4/4 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Blood and Lymphatic	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	3	1/4 (25%)	1	1/4 (25%)	1
Cardiac disorders
cardiac	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	8/41 (19.5%)	12	0/4 (0%)	0	1/4 (25%)	2
Endocrine disorders
Endocrine	1/4 (25%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/41 (4.9%)	2	0/4 (0%)	0	0/4 (0%)	0
Eye disorders
Eye	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	1/41 (2.4%)	1	0/4 (0%)	0	1/4 (25%)	1
Gastrointestinal disorders
Gastrointestinal	4/4 (100%)	8	2/3 (66.7%)	4	1/4 (25%)	2	2/4 (50%)	6	32/41 (78%)	67	3/4 (75%)	5	4/4 (100%)	14
General disorders
General Disorders	3/4 (75%)	4	1/3 (33.3%)	2	2/4 (50%)	2	2/4 (50%)	3	33/41 (80.5%)	61	3/4 (75%)	4	4/4 (100%)	4
Hepatobiliary disorders
Hepatobiliary	1/4 (25%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	2/41 (4.9%)	2	0/4 (0%)	0	0/4 (0%)	0
Immune system disorders
Immune System	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/41 (0%)	0	0/4 (0%)	0	1/4 (25%)	1
Infections and infestations
Infections and Infestations	1/4 (25%)	1	0/3 (0%)	0	1/4 (25%)	1	1/4 (25%)	1	14/41 (34.1%)	17	1/4 (25%)	1	1/4 (25%)	2
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural Complications	0/4 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	5/41 (12.2%)	6	0/4 (0%)	0	0/4 (0%)	0
Investigations
Investigations	1/4 (25%)	4	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	18/41 (43.9%)	31	1/4 (25%)	1	1/4 (25%)	1
Metabolism and nutrition disorders
Metabolism	3/4 (75%)	3	1/3 (33.3%)	1	1/4 (25%)	3	0/4 (0%)	0	17/41 (41.5%)	22	2/4 (50%)	2	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal	2/4 (50%)	2	0/3 (0%)	0	0/4 (0%)	0	1/4 (25%)	1	21/41 (51.2%)	37	0/4 (0%)	0	1/4 (25%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm	1/4 (25%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	6/41 (14.6%)	6	1/4 (25%)	1	0/4 (0%)	0
Nervous system disorders
Nervous System	1/4 (25%)	4	0/3 (0%)	0	0/4 (0%)	0	3/4 (75%)	4	31/41 (75.6%)	61	4/4 (100%)	7	3/4 (75%)	6
Psychiatric disorders
Phychiatric	1/4 (25%)	1	1/3 (33.3%)	1	1/4 (25%)	1	0/4 (0%)	0	13/41 (31.7%)	18	0/4 (0%)	0	0/4 (0%)	0
Renal and urinary disorders
Renal and Urinary	2/4 (50%)	2	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	9/41 (22%)	10	0/4 (0%)	0	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory	2/4 (50%)	3	0/3 (0%)	0	0/4 (0%)	0	2/4 (50%)	2	18/41 (43.9%)	26	1/4 (25%)	2	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Skin and Subcutaneous	1/4 (25%)	1	2/3 (66.7%)	2	1/4 (25%)	1	2/4 (50%)	2	14/41 (34.1%)	20	1/4 (25%)	1	1/4 (25%)	1
Vascular disorders
Vascular	1/4 (25%)	1	0/3 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	8/41 (19.5%)	10	1/4 (25%)	1	1/4 (25%)	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.