Obatoclax Mesylate and Topotecan Hydrochloride in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer or Advanced Solid Tumors

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00521144
• Collaborator: (none)
• Enrollment: 22
• Locations: 2
• Arm: 1
• Duration (Months): 36
• Patients Per Site: 11
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase I/II trial is studying the side effects and best dose of obatoclax mesylate when given together with topotecan hydrochloride and to see how well they work in treating patients with relapsed or refractory small cell lung cancer or advanced solid tumors. Obatoclax mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with topotecan hydrochloride may help kill more tumor cells

Condition or Disease	Intervention/Treatment	Phase
Recurrent Small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific	Drug: obatoclax mesylate; Drug: topotecan hydrochloride; Other: laboratory biomarker analysis	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the maximum tolerated dose, recommended phase II dose, and toxicity profile of obatoclax mesylate when administered with topotecan hydrochloride in patients with advanced solid tumors. (Phase I) II. Determine the response rate in patients with relapsed or refractory small cell lung cancer treated with obatoclax mesylate and topotecan hydrochloride. (Phase II)

SECONDARY OBJECTIVES:

1. Evaluate the expression of pro- and anti-apoptotic proteins which may correlate with obatoclax mesylate sensitivity or resistance.

OUTLINE: This is a phase I dose-escalation study of obatoclax mesylate followed by a phase II study.

PHASE I (solid tumor): Patients receive obatoclax mesylate IV over 3 hours on day 1 OR days 1 and 3 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II (small cell lung cancer): Patients receive obatoclax mesylate and topotecan hydrochloride at the recommended phase II dose (RPTD) determined in phase I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples from patients with small cell lung cancer may be collected at baseline for correlative studies. Tissue samples are analyzed for biomarkers and protein expression of Bcl-2, Bcl-Xl, MCL-1, Bax, Bad, c-Myc, L-Myc, and N-Myc by immunohistochemistry.

After completion of study treatment, patients are followed for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzyme inhibitor therapy and chemotherapy) Patients receive obatoclax mesylate IV over 3 hours on day 1 OR days 1 and 3 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity	Drug: obatoclax mesylate; Given IV; Other Names: GX15-070MS ; Drug: topotecan hydrochloride; Given IV; Other Names: hycamptamine Hycamtin SKF S-104864-A TOPO ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (Phase II) [Every 6 weeks, assessed up to 30 days]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR +PR

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

• Advanced solid tumor (phase I)

• Topotecan hydrochloride must be an appropriate treatment for this cancer

• Small cell lung cancer (SCLC) (phase II)

• Progressed after one prior platinum-based chemotherapy regimen

• Pathology materials (tumor tissue) will be used for correlative studies, if available

• No progressive brain metastases

• Treated brain metastases allowed provided patient is neurologically stable and does not require steroids

• No leptomeningeal involvement

• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

• Leukocytes ≥ 3,000/mcL

• Absolute neutrophil count ≥ 1,500/mcL

• Platelet count ≥ 100,000/mcL

• Total bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Fertile patients must use effective double barrier method of contraception during and for 3 months after completion of study therapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered

• At least 4 weeks since prior radiotherapy and recovered

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents or anticancer therapy

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biological composition to obatoclax mesylate or topotecan hydrochloride (e.g., irinotecan)

• Concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situations that would limit compliance with study requirements

• History of seizure disorder or other neurological dysfunction (except peripheral neuropathy)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital	Baltimore	Maryland	United States	21231
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lee Krug, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00521144
• Other Study ID Numbers: NCI-2009-00252; 07-082; CDR0000561779; NCT01645657
• First Posted: Aug 27, 2007
• Last Update Posted: May 5, 2015
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Topotecan; Obatoclax

Study Results

Participant Flow

Recruitment Details	Protocol Open to Accrual 8/7/2007 Primary Completion Date 8/10/2010 Recruitment Location at medical clinic

Arm/Group Title	Phase I; Level 1: Obatoclax Mesylate + Topetecan	Phase I; Level 2: Obatoclax Mesylate + Topetecan	Phase I; Level 3: Obatoclax Mesylate + Topetecan	Phase I; Level 4: Obatoclax Mesylate + Topotecan	Phase II Obatoclax Mesylate + Topotecan in SCLC
Arm/Group Description	Level 1: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 2: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 3: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 + 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 4: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 + 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Obatoclax Mesylate 14 + 14 mg/m2 and Topotecan 1.25 mg/m2
Period Title: Overall Study
STARTED	6	5	3	1	7
COMPLETED	2	2	1	0	0
NOT COMPLETED	4	3	2	1	7

Baseline Characteristics

Arm/Group Title	Phase I Obatoclax Mesylate + Topotecan in Solid Tumors Level 1	Phase I Obatoclax Mesylate + Topotecan in Solid Tumors Level 2	Phase I Obatoclax Mesylate + Topotecan in Solid Tumors Level 3	Phase I Obatoclax Mesylate + Topotecan in Solid Tumors Level 4	Phase II Obatoclax Mesylate + Topotecan in SCLC	Total
Arm/Group Description	Level 1: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 2: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 3: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 + 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 4: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 + 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Obatoclax Mesylate 14 + 14 mg/m2 and Topotecan 1.25 mg/m2	Total of all reporting groups
Overall Participants	6	5	3	1	7	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 83.3%	3 60%	2 66.7%	0 0%	4 57.1%	14 63.6%
>=65 years	1 16.7%	2 40%	1 33.3%	1 100%	3 42.9%	8 36.4%
Sex: Female, Male (Count of Participants)
Female	5 83.3%	1 20%	1 33.3%	1 100%	6 85.7%	14 63.6%
Male	1 16.7%	4 80%	2 66.7%	0 0%	1 14.3%	8 36.4%
Region of Enrollment (participants) [Number]
United States	6 100%	5 100%	3 100%	1 100%	7 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Phase II)
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR +PR
Time Frame	Every 6 weeks, assessed up to 30 days

Outcome Measure Data

Analysis Population Description

Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

Arm/Group Title	Phase I; Level 1: Obatoclax Mesylate + Topetecan	Phase I; Level 2: Obatoclax Mesylate + Topetecan	Phase I; Level 3: Obatoclax Mesylate + Topetecan	Phase 1; Level 4: Obatoclax Mesylate + Topotecan	Phase II Obatoclax Mesylate + Topotecan in SCLC
Arm/Group Description	Level 1: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 2: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Level 3: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 + 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 + 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2	Obatoclax Mesylate 14 + 14 mg/m2 and Topotecan 1.25 mg/m2
Measure Participants	6	5	3	0	7
Number [participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Arm/Group Title	Phase I; Level 1: Obatoclax Mesylate + Topotecan		Phase I; Level 2: Obatoclax Mesylate + Topotecan		Phase I; Level 3: Obatoclax Mesylate + Topotecan		Phase I; Level 4: Obatoclax Mesylate + Topotecan		Phase II Obatoclax Mesylate + Topotecan in SCLC
Arm/Group Description	Level 1: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2		Level 2: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2		Level 3: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 14 + 14 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2		Level 4: Obatoclax Mesylate (GX15-070MS) 3 hour infusion, days 1 (and 3), q21 days, 20 + 20 mg/m2: Topotecan days 1-5, q21 days, 1.25 mg/m2		Obatoclax Mesylate 14 + 14 mg/m2 and Topotecan 1.25 mg/m2
All Cause Mortality
	Phase I; Level 1: Obatoclax Mesylate + Topotecan		Phase I; Level 2: Obatoclax Mesylate + Topotecan		Phase I; Level 3: Obatoclax Mesylate + Topotecan		Phase I; Level 4: Obatoclax Mesylate + Topotecan		Phase II Obatoclax Mesylate + Topotecan in SCLC
	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)
Serious Adverse Events
	Phase I; Level 1: Obatoclax Mesylate + Topotecan		Phase I; Level 2: Obatoclax Mesylate + Topotecan		Phase I; Level 3: Obatoclax Mesylate + Topotecan		Phase I; Level 4: Obatoclax Mesylate + Topotecan		Phase II Obatoclax Mesylate + Topotecan in SCLC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		4/5 (80%)		2/3 (66.7%)		0/1 (0%)		4/7 (57.1%)
Blood and lymphatic system disorders
Anemia-Hemoglobin decrease	0/6 (0%)	0	2/5 (40%)	2	1/3 (33.3%)	1	0/1 (0%)	0	0/7 (0%)	0
Cardiac disorders
Atrial Fibrillation	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Atrial flutter	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Gastrointestinal disorders
Abdominal pain	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	2
General disorders
Fatigue	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Fever	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Immune system disorders
Allergic Reaction-Hypersensitivity	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Infections and infestations
Urinary Tract Infection	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Infection, other	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Investigations
ALT, SGPT	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	1/7 (14.3%)	1
Alkaline phosphatase	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	1/7 (14.3%)	2
AST, SGOT	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	2/7 (28.6%)	3
Blood bilirubin increase	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/7 (0%)	0
Metabolism and nutrition disorders
Hyponatremia	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Hypomagnesemia (low magnesium)	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/7 (0%)	0
Hypokalemia	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	0/7 (0%)	0
Dehydration	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Nervous system disorders
Ataxia (incoordination)	2/6 (33.3%)	2	2/5 (40%)	2	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Depressed level of consciousness	1/6 (16.7%)	2	3/5 (60%)	3	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Dysgeusia	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Dizziness	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Psychiatric disorders
Euphoria	3/6 (50%)	4	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Depression	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Renal and urinary disorders
Cystitis	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Voice Alteration	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Death-NOS	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Phase I; Level 1: Obatoclax Mesylate + Topotecan		Phase I; Level 2: Obatoclax Mesylate + Topotecan		Phase I; Level 3: Obatoclax Mesylate + Topotecan		Phase I; Level 4: Obatoclax Mesylate + Topotecan		Phase II Obatoclax Mesylate + Topotecan in SCLC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		3/5 (60%)		2/3 (66.7%)		0/1 (0%)		7/7 (100%)
Gastrointestinal disorders
Constipation	2/6 (33.3%)	3	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	3
Diarrhea	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Mucositis-oral	1/6 (16.7%)	2	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Nausea	4/6 (66.7%)	6	2/5 (40%)	4	1/3 (33.3%)	1	0/1 (0%)	0	3/7 (42.9%)	6
Vomiting	2/6 (33.3%)	2	2/5 (40%)	3	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	3
Heartburn/dyspepsia	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
General disorders
Fatigue	4/6 (66.7%)	6	2/5 (40%)	4	2/3 (66.7%)	3	0/1 (0%)	0	5/7 (71.4%)	7
Infections and infestations
Mucosal Infection	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Investigations
White blood cell count decrease	3/6 (50%)	3	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	6/7 (85.7%)	14
Neutrophil count decrease	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	7
Platelet count decrease	1/6 (16.7%)	1	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	6/7 (85.7%)	16
ALT, SGPT	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
AST, SGOT	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Alkaline phosphatase	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	4/7 (57.1%)	8
Lymphocyte count decrease	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Metabolism and nutrition disorders
Anorexia	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Hyperglycemia	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	4
Anemia-Hemoglobin decrease	3/6 (50%)	6	2/5 (40%)	2	0/3 (0%)	0	0/1 (0%)	0	4/7 (57.1%)	22
Albumin, low (hypoalbuminemia)	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	4
Musculoskeletal and connective tissue disorders
Back Pain	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Bone pain	1/6 (16.7%)	1	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Chest wall pain	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Pain in extremity	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Nervous system disorders
Ataxia (incoordination)	5/6 (83.3%)	11	2/5 (40%)	6	2/3 (66.7%)	4	0/1 (0%)	0	7/7 (100%)	21
Depressed level of consciousness	4/6 (66.7%)	7	3/5 (60%)	6	1/3 (33.3%)	1	0/1 (0%)	0	7/7 (100%)	31
Dysgeusia (taste alteration)	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Dizziness	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Speech impairment	1/6 (16.7%)	1	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Neuropathy-sensory	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	3/7 (42.9%)	3
Pain-Head/Headache	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Extrapyramidal disorder	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Psychiatric disorders
Depression	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Euphoria	3/6 (50%)	3	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Psychosis	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Mood alteration-Agitation	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1
Renal and urinary disorders
Glomerular filtration rate decrease	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	3/7 (42.9%)	3
Dyspnea	3/6 (50%)	3	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	4/7 (57.1%)	6
Hemorrhage, Nose	0/6 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	2	0/1 (0%)	0	3/7 (42.9%)	3
Sinusitis	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Hypoxia	0/6 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	2
Erythema multiforme	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0
Rash/desquamation	1/6 (16.7%)	1	0/5 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0

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.