Akt/ERK Inhibitor ONC201 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02420795
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Actual Duration (Months): 60.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and the best dose of v-akt murine thymoma viral oncogene homolog (Akt)/mitogen-activated protein kinase 1(ERK) inhibitor ONC201 and to see how well it works in treating patients with non-Hodgkin's lymphoma that has returned after a period of improvement or does not respond to treatment. Akt/ERK inhibitor ONC201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Lymphoma; Gastric Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Splenic Mantle Cell Lymphoma	Drug: Akt/ERK Inhibitor ONC201; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine recommended phase II dose for oral ONC201 (Akt/ERK inhibitor ONC201) in patients with relapsed/refractory lymphomas. (Phase I) II. To identify toxicities associated with oral ONC201 in patients with relapsed/refractory lymphomas. (Phase I) III. To determine the objective response rate to ONC201 in patients with relapsed/refractory lymphomas. (Phase

SECONDARY OBJECTIVES:

1. To determine the pharmacokinetics (PK) of oral ONC201 following administration. (Phase I)
2. To observe the anti-tumor effects of oral ONC201, if any occur, in patients with relapsed/refractory lymphomas. (Phase I) III. Confirm tolerability of recommended phase II dose. (Phase II) IV. Assess clinical outcomes associated with ONC201 treatment in patients with relapsed/refractory lymphomas. (Phase II) V. Correlate clinical outcome with tumor and serum biomarkers. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive Akt/ERK inhibitor ONC201 orally (PO) on day 1 of every cycle or day 1 of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

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/II Study of Oral ONC201 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
• Actual Study Start Date: Nov 3, 2015
• Actual Primary Completion Date: Nov 16, 2020
• Actual Study Completion Date: Nov 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (Akt/ERK inhibitor ONC201) Patients receive Akt/ERK inhibitor ONC201 PO on day 1 of every cycle or day 1 of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Akt/ERK Inhibitor ONC201; Given PO; Other Names: ONC201 TIC10 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Recommended Phase 2 Dose (RP2D) (Phase I) [21 days]

2. Number of Participants With Overall Response Rate (Phase 1 and 2) [Up to 63 days (first 3 courses)]

   Defined as either progressive disease or stable disease observed assessed by the Revised International Workshop Standardization Response Criteria for non-Hodgkin lymphoma.

Secondary Outcome Measures

1. Overall Survival (OS) [every 3 months for 1 year, then every 6 months, up to 3 years]

   Overall survival is the time in months from start of study treatment to date of death due to any cause.

2. Progression-free Survival (PFS)- (Phase 2) [every 3 months for 1 year, then every 6 months, up to 6 years]

   Progression free survival is defined as time in weeks from start of study treatment to first documentation of objective tumor progression or up to death due to any cause, whichever occurs first.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Phase 1 and Phase 2: confirmed diagnosis of previously treated relapsed and/or refractory lymphoma; patients with central nervous system (CNS) lymphoma are included

• Patient with leukemia phase (peripheral blood involvement), CNS lymphoma [including cerebrospinal fluid (CSF)-only disease], non-measurable disease, gastrointestinal (GI) mantle cell lymphoma (MCL), or bone marrow (BM) MCL are also eligible; gastrointestinal or bone marrow or spleen only patients are allowable and will be analyzed separately

• All adverse events related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to =< grade 1, except for alopecia

• Patients must be willing to receive transfusions of blood products

• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

• Serum creatinine < 2.0 mg/dl

• Serum bilirubin < 1.5 mg/dl

• Platelet count > 50,000/mm^3

• Absolute neutrophil count (ANC) > 1,000/mm^3

• Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present

• Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test and must be willing to use acceptable methods of birth control during the study and for 90 days after the last dose of study treatment; acceptable methods of birth control include condoms with birth control foam, birth control pills, implantable or injectable birth control, birth control patch, intrauterine device (IUD), or diaphragm with spermicidal gel; male patients must use an effective barrier method of contraception (i.e. , condoms with birth control foam or diaphragm with spermicidal gel) during the study and for 90 days following the last dose of study treatment if sexually active with a female of childbearing potential; contraception must be in place at least 2 weeks prior to initiating study treatment; a female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Patient must be English-speaking [MD Anderson Symptom Inventory (MDASI) completion only]

Exclusion Criteria:

• Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled infection, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active hemorrhage, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk or would prevent the subject from signing the informed consent form

• Pregnant or breast feeding females

• Use of any standard/experimental anti-lymphoma drug therapy, including steroids (dexamethasone dose >= 4 mg/day or prednisone >= 20 mg/day), within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment; hydroxyurea is permitted up to 24 hours before the first dose of study drug in patients with rapidly-proliferating disease

• Prior allogeneic stem cell transplant (SCT) within 16 weeks or autologous SCT within 8 weeks of initiation of therapy (patients that require immunosuppressive therapy are not eligible within 60 days of therapy)

• History of human immunodeficiency virus (HIV) infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody); hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation; HIV screening is not required for this study

• Significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to enrollment

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other gastrointestinal condition that could interfere with the absorption and metabolism of ONC201

• Major surgery within 4 weeks of initiation of therapy

• The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent; investigator discretion is allowed

• Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to second (2nd) degree atrioventricular (AV) block type II, third (3rd) degree block, QT prolongation (corrected QT [QTc] > 500 msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with active atrial fibrillation will be excluded; the protocol excludes patients who have within the past year had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin equivalent vitamin K antagonist

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients

• Acute infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of study

• Active alcoholism or use of recreational drug (evaluated by history taking)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Luhua (Michael) Wang, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 13, 2018

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02420795
• Other Study ID Numbers: 2014-0630; NCI-2015-00706; 204666; 20152142; 1-909048-1; 1159132; 2014-0630
• First Posted: Apr 20, 2015
• Last Update Posted: Apr 4, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Recurrence; TIC10 compound

Study Results

Participant Flow

Recruitment Details	Patients recruited at MD Anderson Lymphoma clinic from November 2015 through April 2018
Pre-assignment Detail	A total of 16 participants consented for the protocol, 11 participated on the study, 4 of the participants were screen failures and 1 withdrew consent.

Arm/Group Title	ONC201 125 mg	ONC201 250 mg	ONC201 625 mg
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 125 mg PO on day 1 of every cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 250 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 625 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	4	2	5
COMPLETED	0	0	0
NOT COMPLETED	4	2	5

Baseline Characteristics

Arm/Group Title	ONC201 125 mg	ONC201 250 mg	ONC201 625 mg	Total
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 125 mg PO on day 1 of every cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 250 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 625 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	4	2	5	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 25%	0 0%	1 20%	2 18.2%
>=65 years	3 75%	2 100%	4 80%	9 81.8%
Sex: Female, Male (Count of Participants)
Female	1 25%	0 0%	2 40%	3 27.3%
Male	3 75%	2 100%	3 60%	8 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	1 20%	1 9.1%
Not Hispanic or Latino	3 75%	2 100%	4 80%	9 81.8%
Unknown or Not Reported	1 25%	0 0%	0 0%	1 9.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	4 100%	2 100%	5 100%	11 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	2 100%	5 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	Recommended Phase 2 Dose (RP2D) (Phase I)
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ONC201 125 mg
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 125 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	4
Number [mg]	125

2. Primary Outcome

Title	Number of Participants With Overall Response Rate (Phase 1 and 2)
Description	Defined as either progressive disease or stable disease observed assessed by the Revised International Workshop Standardization Response Criteria for non-Hodgkin lymphoma.
Time Frame	Up to 63 days (first 3 courses)

Outcome Measure Data

Analysis Population Description

1 patient passed away prior to restaging in Phase 2 Arm B

Arm/Group Title	ONC201 125 mg	ONC201 250 mg	ONC201 625 mg
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 125 mg PO on day 1 of every cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 250 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 625 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	4	2	5
Progressive Disease	3 75%	1 50%	3 60%
Stable Disease	1 25%	1 50%	1 20%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is the time in months from start of study treatment to date of death due to any cause.
Time Frame	every 3 months for 1 year, then every 6 months, up to 3 years

Outcome Measure Data

Analysis Population Description

Overall survival for each arm measured in months

Arm/Group Title	ONC201 125 mg	ONC201 250 mg	ONC201 625 mg
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 125 mg PO on day 1 of every cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 250 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive Akt/ERK inhibitor ONC201 625 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	2	4	5
Median (Full Range) [months]	29	15	24

4. Secondary Outcome

Title	Progression-free Survival (PFS)- (Phase 2)
Description	Progression free survival is defined as time in weeks from start of study treatment to first documentation of objective tumor progression or up to death due to any cause, whichever occurs first.
Time Frame	every 3 months for 1 year, then every 6 months, up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ONC201 625 mg
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 625 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	5
Median (Full Range) [weeks]	5

Adverse Events

Time Frame	From the first dose through every 3 months after the last dose of study medication, up to 1 year.
Arm/Group Title	ONC201 125 mg		ONC201 250 mg		ONC201 625 mg
Arm/Group Description	Patients receive Akt/ERK inhibitor ONC201 125 mg PO on day 1 of every cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.		Patients receive Akt/ERK inhibitor ONC201 250 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.		Patients receive Akt/ERK inhibitor ONC201 625 mg PO every 7 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	ONC201 125 mg		ONC201 250 mg		ONC201 625 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/2 (0%)		1/5 (20%)
Serious Adverse Events
	ONC201 125 mg		ONC201 250 mg		ONC201 625 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		1/2 (50%)		1/5 (20%)
Blood and lymphatic system disorders
Anemia	0/4 (0%)		1/2 (50%)		0/5 (0%)
Blood and lymphatic system disorders- Other	0/4 (0%)		1/2 (50%)		0/5 (0%)
General disorders
Dehydration	0/4 (0%)		1/2 (50%)		0/5 (0%)
Edema Limbs	0/4 (0%)		0/2 (0%)		1/5 (20%)
Infections and infestations
Myocardial Infarction	0/4 (0%)		0/2 (0%)		1/5 (20%)
Other (Not Including Serious) Adverse Events
	ONC201 125 mg		ONC201 250 mg		ONC201 625 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		2/2 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Anemia	3/4 (75%)		1/2 (50%)		0/5 (0%)
Blood and lymphatic system disorder	0/4 (0%)		1/2 (50%)		0/5 (0%)
Pancytopenia	0/4 (0%)		1/2 (50%)		0/5 (0%)
Platelet count decreased	1/4 (25%)		1/2 (50%)		2/5 (40%)
Platelet Count Decreased	1/4 (25%)		0/2 (0%)		2/5 (40%)
Cardiac disorders
Myocardial Infarction	0/4 (0%)		0/2 (0%)		1/5 (20%)
Sinus bradycardia	1/4 (25%)		0/2 (0%)		0/5 (0%)
Ear and labyrinth disorders
Ear Pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Hearing impaired	0/4 (0%)		1/2 (50%)		0/5 (0%)
Loss of hearing on right ear	1/4 (25%)		0/2 (0%)		0/5 (0%)
Endocrine disorders
Hypothyroidism	0/4 (0%)		0/2 (0%)		1/5 (20%)
Eye disorders
Blurred vision	1/4 (25%)		0/2 (0%)		1/5 (20%)
Redness (both ears)	1/4 (25%)		0/2 (0%)		0/5 (0%)
Gastrointestinal disorders
Abdominal pain	0/4 (0%)		1/2 (50%)		1/5 (20%)
Constipation	1/4 (25%)		1/2 (50%)		1/5 (20%)
Diarrhea	1/4 (25%)		0/2 (0%)		4/5 (80%)
Dry mouth	1/4 (25%)		0/2 (0%)		0/5 (0%)
Dyspepsia	0/4 (0%)		0/2 (0%)		1/5 (20%)
Dysphagia	0/4 (0%)		0/2 (0%)		1/5 (20%)
GI bleeding	0/4 (0%)		1/2 (50%)		0/5 (0%)
Nausea	1/4 (25%)		1/2 (50%)		2/5 (40%)
Vomiting	1/4 (25%)		0/2 (0%)		0/5 (0%)
Acute abdominal pain on lower right	0/4 (0%)		0/2 (0%)		1/5 (20%)
General disorders
AST increased	2/4 (50%)		0/2 (0%)		0/5 (0%)
Back pain	0/4 (0%)		0/2 (0%)		1/5 (20%)
Bug bites	0/4 (0%)		0/2 (0%)		1/5 (20%)
Edema limbs	1/4 (25%)		0/2 (0%)		3/5 (60%)
Edema trunk	1/4 (25%)		0/2 (0%)		0/5 (0%)
Elevated LDH	0/4 (0%)		1/2 (50%)		0/5 (0%)
Fatigue	3/4 (75%)		2/2 (100%)		4/5 (80%)
Fever	0/4 (0%)		0/2 (0%)		1/5 (20%)
Pain	0/4 (0%)		0/2 (0%)		1/5 (20%)
Right carotid artery disease	0/4 (0%)		0/2 (0%)		1/5 (20%)
Runny nose	0/4 (0%)		1/2 (50%)		0/5 (0%)
Weakness	0/4 (0%)		0/2 (0%)		2/5 (40%)
Alkaline phosphatase increased (ALT)	1/4 (25%)		0/2 (0%)		0/5 (0%)
Left hip and thigh pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Left lower back pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Left lower leg pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Left quadrant abdominal pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Left shoulder pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Legs Muscle Cramps	1/4 (25%)		0/2 (0%)		0/5 (0%)
Right Hip Pain	2/4 (50%)		0/2 (0%)		0/5 (0%)
Right Upper Quadrant Pain	1/4 (25%)		0/2 (0%)		0/5 (0%)
Infections and infestations
Splenomegaly	0/4 (0%)		0/2 (0%)		1/5 (20%)
Thrush	0/4 (0%)		1/2 (50%)		0/5 (0%)
Oral Thrush	1/4 (25%)		0/2 (0%)		0/5 (0%)
Injury, poisoning and procedural complications
Fall	0/4 (0%)		0/2 (0%)		1/5 (20%)
Investigations
Creatinine increased	0/4 (0%)		0/2 (0%)		1/5 (20%)
Neutrophil count decreased	0/4 (0%)		1/2 (50%)		1/5 (20%)
Weight loss	0/4 (0%)		0/2 (0%)		2/5 (40%)
Metabolism and nutrition disorders
Appetite change	0/4 (0%)		0/2 (0%)		1/5 (20%)
Dehydration	0/4 (0%)		1/2 (50%)		1/5 (20%)
Hypercalcemia	1/4 (25%)		1/2 (50%)		0/5 (0%)
Hyperglycemia	1/4 (25%)		1/2 (50%)		1/5 (20%)
Hyperkalemia	1/4 (25%)		1/2 (50%)		1/5 (20%)
Hyperuricemia	0/4 (0%)		0/2 (0%)		1/5 (20%)
Hypomagnesemia	0/4 (0%)		1/2 (50%)		1/5 (20%)
Hyponatremia	0/4 (0%)		0/2 (0%)		1/5 (20%)
Musculoskeletal and connective tissue disorders
Myalgia	2/4 (50%)		1/2 (50%)		1/5 (20%)
Left ankle	0/4 (0%)		0/2 (0%)		1/5 (20%)
Nervous system disorders
Anxiety	0/4 (0%)		0/2 (0%)		2/5 (40%)
Dizziness	0/4 (0%)		0/2 (0%)		2/5 (40%)
Peripheral Sensory Neuoropathy	0/4 (0%)		0/2 (0%)		1/5 (20%)
Numbness	1/4 (25%)		0/2 (0%)		0/5 (0%)
Numbness/Tingling	0/4 (0%)		2/2 (100%)		0/5 (0%)
Psychiatric disorders
Insomnia	0/4 (0%)		0/2 (0%)		1/5 (20%)
Memory changes	0/4 (0%)		1/2 (50%)		1/5 (20%)
Memory impairment	0/4 (0%)		0/2 (0%)		1/5 (20%)
Sleep disturbance	0/4 (0%)		0/2 (0%)		1/5 (20%)
Renal and urinary disorders
BUN increased	1/4 (25%)		0/2 (0%)		0/5 (0%)
Hematuria	1/4 (25%)		0/2 (0%)		0/5 (0%)
Renal insufficiency	1/4 (25%)		1/2 (50%)		0/5 (0%)
Chronic kidney disease (creatinine increased)	0/4 (0%)		0/2 (0%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Cough	0/4 (0%)		1/2 (50%)		0/5 (0%)
Dyspnea	1/4 (25%)		1/2 (50%)		1/5 (20%)
Pleural Effusion	0/4 (0%)		1/2 (50%)		0/5 (0%)
Seasonal allergies	0/4 (0%)		0/2 (0%)		1/5 (20%)
Sore throat	0/4 (0%)		0/2 (0%)		1/5 (20%)
Wheezing	0/4 (0%)		0/2 (0%)		1/5 (20%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/4 (25%)		0/2 (0%)		0/5 (0%)
Ecchymosis (bilateral forearms)	0/4 (0%)		0/2 (0%)		1/5 (20%)
Vascular disorders
Hypertension	1/4 (25%)		1/2 (50%)		1/5 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.