Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

• Sponsor: Merrimack Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00734305
• Collaborator: Sanofi (Industry)
• Enrollment: 44
• Locations: 3
• Arm: 1
• Duration (Months): 62
• Patients Per Site: 14.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: MM-121	Phase 1

Detailed Description

Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 2 dose was identified. The study initially explored a dosing schedule every 7-days, which may have been modified to longer intervals under certain circumstances but did not expand to more than weekly. When the maximum tolerated dose/recommended Phase 2 dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints. There were 3 sites that participated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D	Drug: MM-121; Dose escalation Frequency - once weekly; Other Names: Seribantumab, SAR256212

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate and Duration [Time from first dose to date of progression, with a median of 7.1 weeks]

   To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a >20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression. NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured.

2. Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities [From date of first dose to 30 days after termination, the longest 47 weeks]

   Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6. Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.

Secondary Outcome Measures

1. To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy [From date of first dose to 30 days after termination, the longest 47 weeks]

   To establish the safety of escalating doses of MM-121 administered as a monotherapy in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.

2. To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121 [At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients]

   Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg). Immunogenicity data is not available.

3. To Determine the Pharmacokinetic Parameters of MM-121 [At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients]

   Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The AUC is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy

• Patients must be > 18 years of age

• Patients or their legal representatives must be able to understand and sign an informed consent form

• Patients must have evaluable or measurable tumor(s)

• Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy.

• Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-121 (an effective form of contraception is an oral contraceptive or a double barrier method)

In addition, patients to be enrolled the Expansion Cohort must have/be:

• Advanced/metastatic breast cancer with histological/cytological documentation of ER-, PR-, Her2/neu non-over-expressing breast cancer (triple negative breast cancer); OR,

• Patients must have advanced/metastatic breast cancer with histologically or cytologically confirmed ER+ and/or PR+, Her2/neu non-over-expxressing OR,

• Patients must have advanced/metastatic histological confirmation of epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer; OR,

• Additional tumor types such as metastatic colorectal, advanced non small cell lung cancer, and others may be considered on a per-patient basis

• Tumor tissue amenable to biopsy

• Platelet counts, partial thromboplastin time (PTT) and international normalized ratio (INR) within normal limits.

• Willing to undergo tumor biopsy twice (once before and once after treatment with MM-121)

• Blocks of archived formalin-fixed, paraffin-embedded, unstained tumor tissue available for submission. Patients with no available archived tumor tissue available must receive Sponsor approval prior to enrollment.

Exclusion Criteria:

• Patients for whom potentially curative antineoplastic therapy is available

• Patients who are pregnant or lactating

• Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)

• Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial

• NYHA Class III or IV congestive heart failure or LVEF < 55%

• Known HIV, hepatitis B or C (active, previously treated or both)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115-6084
2	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
3	The Vanderbilt-Ingram Cancer Center	Nashville,	Tennessee	United States	37232

Sponsors and Collaborators

• Merrimack Pharmaceuticals
• Sanofi

Investigators

• Principal Investigator: Crystal Denlinger, MD, Fox Chase Cancer Center
• Principal Investigator: Kwok Kin Wong, MD, Dana-Farber Cancer Institute
• Principal Investigator: Keedy L Vicki, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merrimack Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00734305
• Other Study ID Numbers: MM-121-01-100; MM-121
• First Posted: Aug 14, 2008
• Last Update Posted: Sep 1, 2016
• Last Verified: Aug 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Merrimack Pharmaceuticals: cancer, solid tumors, oncology, Phase I, ErbB3, HER3; (erbB-3, HER-3)
• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Arm/Group Title	Dose Escalation: Cohort 1	Dose Escalation: Cohort 2	Dose Escalation: Cohort 3	Dose Escalation: Cohort 4	Dose Escalation: Cohort 5	Dose Escalation: Cohort 6	Expansion Cohort
Arm/Group Description	MM-121: 3.2 mg/kg IV QW	MM-121: 6 mg/kg IV QW	MM-121: 10 mg/kg IV QW	MM-121: 15 mg/kg IV QW	MM-121: 20 mg/kg IV QW	MM-121: 40 mg/kg IV loading dose on C1W1 followed by weekly maintenance doses of 20 mg/kg IV QW	(Highest tested dose in absence of reaching maximum tolerated dose) 40 mg/kg IV loading dose on C1W1 followed by weekly maintenance doses of 20 mg/kg IV QW
Period Title: Overall Study
STARTED	7	3	4	3	5	4	18
COMPLETED	6	3	4	3	5	4	18
NOT COMPLETED	1	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	MM-121 Dose Escalation	MM-121 Expansion Cohort	Total
Arm/Group Description	MM-121: Dose escalation Frequency - once weekly IV	Expansion cohort at recommended phase 2 dose	Total of all reporting groups
Overall Participants	25	18	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (10.82)	58.5 (8.08)	59.85 (9.45)
Sex: Female, Male (Count of Participants)
Female	12 48%	15 83.3%	27 62.8%
Male	13 52%	3 16.7%	16 37.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4%	1 5.6%	2 4.7%
Not Hispanic or Latino	24 96%	17 94.4%	41 95.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 8%	1 5.6%	3 7%
White	23 92%	17 94.4%	40 93%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%	18 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate and Duration
Description	To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response is defined as a >20% decrease in tumor burden from baseline and a Complete Response is defined as complete disappearance of tumor burden from baseline. Duration of response is defined as the length of time in weeks from observation of response until progression. NOTE: because no patients experienced an objective response as shown below, duration of response is not presented. No duration of response could be measured.
Time Frame	Time from first dose to date of progression, with a median of 7.1 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Escalation: Cohort 1	Dose Escalation: Cohort 2	Dose Escalation: Cohort 3	Dose Escalation: Cohort 4	Dose Escalation: Cohort 5	Dose Escalation: Cohort 6	MM-121 Expansion Cohort
Arm/Group Description	MM-121: 3.2 mg/kg IV QW	MM-121 6 mg/kg IV QW	MM-121 10 mg/kg IV QW	MM-121 15 mg/kg IV QW	MM-121 20 mg/kg IV QW	MM-121 40 mg/kg IV loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV weekly maintenance doses	Expansion cohort at recommended phase 2 dose
Measure Participants	6	3	4	3	5	4	18
Number [participants with objective response]	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Description	Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort from cohort 1-6. Cohort 1 began at 3.2 mg/kg IV QW and the dose escalated in separate cohorts from 6 mg/kg IV QW, 10 mg/kg IV QW, 15 mg/kg IV QW, 20 mg/kg IV QW, to the highest scheduled testing dose at 40 mg/kg one-time loading dose on cycle 1, week 1 followed by 20 mg/kg IV QW maintenance doses. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose and was used to open the expansion cohort.
Time Frame	From date of first dose to 30 days after termination, the longest 47 weeks

Outcome Measure Data

Analysis Population Description

All participants in the 6 cohorts of dose escalation

Arm/Group Title	Dose Escalation: All Participants
Arm/Group Description	MM-121: Dose escalation Frequency - once weekly
Measure Participants	25
Number [mg/kg]	40

3. Secondary Outcome

Title	To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
Description	To establish the safety of escalating doses of MM-121 administered as a monotherapy in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
Time Frame	From date of first dose to 30 days after termination, the longest 47 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	MM-121 3.2 mg/kg IV QW	MM-121: 6 mg/kg IV QW	MM-121: 10 mg/kg IV QW	MM-121: 15 mg/kg IV QW	MM-121: 20 mg/kg IV QW	MM-121: 40 mg/kg IV loading dose followed by 20 mg/kg IV QW maintenance doses
Measure Participants	6	3	4	3	5	4
Number [participants reporting DLTs]	1 4%	0 0%	0 0%	0 NaN	0 NaN	0 NaN

4. Secondary Outcome

Title	To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
Description	Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg). Immunogenicity data is not available.
Time Frame	At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients

Outcome Measure Data

Analysis Population Description

All patients. NOTE: There are 22 patients included in the final cohort (4 patients in dose escalation portion Cohort 6 + 18 patients in Expansion Cohort), as PK analysis was performed per dose level and not per cohort. Cohort 6 and the Expansion Cohort were administered the same dose, and therefore the analysis reflects all 22 patients.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Recommended Phase 2 Dose
Arm/Group Description	MM-121 3.2 mg/kg IV QW	MM-121: 6 mg/kg IV QW	MM-121: 10 mg/kg IV QW	MM-121: 15 mg/kg IV QW	MM-121: 20 mg/kg IV QW	MM-121: 40 mg/kg IV loading dose followed by 20 mg/kg IV QW maintenance doses Combination of Cohort 6 patients (N=4) and Expansion Cohort Patients (N=18) that received this dose level.
Measure Participants	6	3	4	3	5	22
Geometric Mean (Geometric Coefficient of Variation) [ug/mL]	78.1 (16.7)	291 (42.4)	410 (40.7)	409 (17.0)	518 (26.2)	836 (23.9)

5. Secondary Outcome

Title	To Determine the Pharmacokinetic Parameters of MM-121
Description	Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. The AUC is presented and was calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (3.2 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 40/20 mg/kg).
Time Frame	At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients

Outcome Measure Data

Analysis Population Description

All patients. NOTE: There are 22 patients included in the final cohort (4 patients in dose escalation portion Cohort 6 + 18 patients in Expansion Cohort), as PK analysis was performed per dose level and not per cohort. Cohort 6 and the Expansion Cohort were administered the same dose, and therefore the analysis reflects all 22 patients.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Recommended Phase 2 Dose
Arm/Group Description	MM-121 3.2 mg/kg IV QW	MM-121: 6 mg/kg IV QW	MM-121: 10 mg/kg IV QW	MM-121: 15 mg/kg IV QW	MM-121: 20 mg/kg IV QW	MM-121: 40 mg/kg IV loading dose followed by 20 mg/kg IV QW maintenance doses Combination of Cohort 6 patients (N=4) and Expansion Cohort Patients (N=18) that received this dose level.
Measure Participants	6	3	4	3	5	22
Geometric Mean (Geometric Coefficient of Variation) [hr* ug/mL]	4850 (24.5)	14800 (43.8)	24000 (40.4)	28100 (19.9)	32700 (23.6)	65600 (22.9)

Adverse Events

Time Frame	AEs were collected from a patient's first dose until 30 days after treatment termination. SAEs were collected from time of informed consent until 30 days after termination. If related, events could be reported at any time after termination.
Adverse Event Reporting Description	All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for ~1 year after termination.
Arm/Group Title	All Participatants
Arm/Group Description	Dose Escalation cohort participants + Expansion cohort participants
All Cause Mortality
	All Participatants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participatants
	Affected / at Risk (%)	# Events
Total	14/43 (32.6%)
Cardiac disorders
Arrhythmia	1/43 (2.3%)
Gastrointestinal disorders
Abdominal Pain	1/43 (2.3%)
Abdominal Pain Lower	1/43 (2.3%)
Pancreatitis Acute	1/43 (2.3%)
Vomiting	1/43 (2.3%)
General disorders
Disease Progression	4/43 (9.3%)
Pyrexia	1/43 (2.3%)
Metabolism and nutrition disorders
Dehydration	1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Flank Pain	1/43 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Neoplasm Progression	2/43 (4.7%)
Tumor Pain	1/43 (2.3%)
Psychiatric disorders
Confusional State	1/43 (2.3%)
Renal and urinary disorders
Hydronephrosis	1/43 (2.3%)
Renal Failure	1/43 (2.3%)
Ureteric Obstruction	1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea Exertional	1/43 (2.3%)
Pleural Effusion	1/43 (2.3%)
Vascular disorders
Hypotension	1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	All Participatants
	Affected / at Risk (%)	# Events
Total	43/43 (100%)
Blood and lymphatic system disorders
Anemia	5/43 (11.6%)
Gastrointestinal disorders
Nausea	20/43 (46.5%)
Diarrhea	16/43 (37.2%)
Vomiting	12/43 (27.9%)
Abdominal Pain	7/43 (16.3%)
Dyspepsia	5/43 (11.6%)
Constipation	4/43 (9.3%)
Stomatitis	4/43 (9.3%)
General disorders
Fatigue	21/43 (48.8%)
Disease Progression	4/43 (9.3%)
Peripheral Edema	4/43 (9.3%)
Asthenia	3/43 (7%)
Chills	3/43 (7%)
Infections and infestations
Urinary Tract Infection	4/43 (9.3%)
Investigations
Hemoglobin Decreased	10/43 (23.3%)
Weight Decreased	9/43 (20.9%)
Blood Alkaline Phosphatase Increased	5/43 (11.6%)
Aspartate Aminotransferase Increased	4/43 (9.3%)
Activated Partial Thrombostatin Time Prolonged	3/43 (7%)
Blood Creatinine Increased	3/43 (7%)
Ejection Fraction Decreased	3/43 (7%)
Electrocardiogram Qt Prolonged	3/43 (7%)
Metabolism and nutrition disorders
Decreased Appetite	12/43 (27.9%)
Hypokalemia	11/43 (25.6%)
Hyperglycemia	10/43 (23.3%)
Hypoalbuminemia	8/43 (18.6%)
Dehydration	7/43 (16.3%)
Hypomagnesemia	7/43 (16.3%)
Hypocalcemia	6/43 (14%)
Hyponatremia	4/43 (9.3%)
Musculoskeletal and connective tissue disorders
Back Pain	6/43 (14%)
Muscle Spasms	4/43 (9.3%)
Musculoskeletal Pain	4/43 (9.3%)
Flank Pain	3/43 (7%)
Pain in Extremity	3/43 (7%)
Nervous system disorders
Dizziness	4/43 (9.3%)
Headache	4/43 (9.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	7/43 (16.3%)
Dyspnea Exertional	5/43 (11.6%)
Cough	3/43 (7%)
Rhinitis Allergic	3/43 (7%)
Wheezing	3/43 (7%)
Skin and subcutaneous tissue disorders
Rash	10/43 (23.3%)
Vascular disorders
Hypotension	3/43 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.