Ofatumumab as Primary Therapy of Chronic Graft Versus Host Disease

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01680965
• Collaborator: (none)
• Enrollment: 44
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 117.6
• Patients Per Site: 11
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To study the safety and side effects of Ofatumumab in the treatment of chronic graft-versus-host disease (GvHD). This study will also evaluate effectiveness of Ofatumumab when added to standard steroid treatment for chronic graft-versus-host disease

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft Versus Host Disease	Drug: Ofatumumab	Phase 1/Phase 2

Detailed Description

This is a phase I-II trial to examine the safety and efficacy of prednisone and escalating dose of ofatumumab for the primary therapy of chronic GVHD.

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: Ofatumumab in Combination With Glucocorticoids for Primary Therapy of Chronic Graft Versus Host Disease
• Actual Study Start Date: Nov 14, 2012
• Actual Primary Completion Date: Aug 1, 2020
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ofatumumab Phase I: Escalating dose of ofatumumab Phase II: Maximum tolerated dose (MTD) of Ofatumumab	Drug: Ofatumumab; Phase I: test an escalating dose of ofatumumab at cohorts of 300 mg, 700 mg, and 1000 mg given on day 0 and 14 of study. Phase II: Ofatumumab MTD on day 0 and 14; patients will be followed for total of 24 months (months 1, 3, 6, 12 after therapy, then at 18 and 24 months following therapy)

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose of Ofatumumab [within 21 days of initiation]

   Maximum Tolerated Dose was determined by increasing doses, beginning at 300 mg on day 0 and day 14, then increasing to 700 mg on day 0 and day 14 and finally 1000 mg on day 0 and day 14.

2. Participants Response Rates [6 months following initiation of Ofatumumab]

   Overall response rate (ORR) at 6 months following initiation of therapy. ORR is the composite outcome of complete response and partial response

Secondary Outcome Measures

1. Overall Survival (OS) at 24 Months [Up to 24 months]

   Overall Survival is defined as the time period from start of treatment to death.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Hematopoietic cell transplantation (HCT) recipients newly requiring systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD

• Participants can be enrolled and begin study therapy with ofatumumab within 14 days from initiation of 1 mg/kg/day prednisone for therapy of chronic GVHD.

Exclusion Criteria:

• Relapse of primary hematologic malignancy that served as indication for HCT.

• Previous systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD

• Prior systemic glucocorticoid therapy for acute GVHD is permitted

• Prior or ongoing systemic immune suppressive agents (including, but not limited to common examples such as calcineurin inhibitors, sirolimus, mycophenolate mofetil) provided for either prevention or treatment of acute GVHD are permitted and part of routine standard of care

• Current active hepatic or biliary disease (with exception of liver disease secondary to chronic GVHD, or patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).

• Patients with abnormal liver function tests due to chronic GVHD are specifically not excluded from the study. This is a common manifestation of chronic GVHD, and thus a major target for the study therapy.

• Treatment with experimental non-FDA approved therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer

• Other past or current solid tumor malignancy

• Have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.

• Prior treatment with anti-cluster of differentiation antigen 20 (CD20) monoclonal antibody or alemtuzumab within 3 months prior to start of therapy.

• Uncontrolled infectious complications not responsive to appropriate antimicrobial therapy.

• History of significant cerebrovascular disease (i.e. stroke or TIA) in the past 6 months or ongoing event with active symptoms or sequelae

• HIV positivity

• Uncontrolled, current significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.

• A history of cardiac disease, such as coronary disease, arrhythmia or congestive heart failure that are on appropriate medical therapy and without evidence of current decompensation are eligible.

• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.

• Those patients with medical conditions that are controlled with medical therapy are eligible.

• Clinically active Hepatitis B defined as positive HBsAg; or positive HBcAb with detectable hepatitis B virus (HBV) DNA viral load. Patients who are HBcAb with undetectable HBV DNA viremia are eligible.

• Positive serology for hepatitis C (HC) defined as a positive test and confirmed by HC recombinant immunoblot assay (RIBA) or hepatitis C virus (HCV) RNA viral load

• Screening laboratory value exclusion criteria: platelets < 50 x 10^{9/L (patients with platelet counts > 50 x 10}9/L supported by platelet transfusion are eligible); neutrophils < 1.0 x 10^{9/L (patients with an absolute neutrophil count > 1.0 x 10}9/L supported by growth factors are eligible); creatinine > 2.0 times upper normal limit; total bilirubin >1.5 times upper normal limit (unless due to chronic GVHD); alanine transaminase (ALT) > 2.0 times upper normal limit (unless due to chronic GVHD); alkaline phosphatase > 2.5 times upper normal limit (unless due to chronic GVHD).

• Women who are pregnant or lactating. Women of childbearing potential must have a negative pregnancy test at screening.

• Women of child bearing potential must undergo pregnancy testing within 7 days of the first dose of study therapy. Women must also undergo pregnancy test at 6 months after the last dose.

• Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.

• Males unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Cancer Center	Phoenix	Arizona	United States	85054
2	H.Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
3	University of Minnesota	Minneapolis	Minnesota	United States	55455
4	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Joseph Pidala, MD, MS, H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 10, 2016

More Information

Additional Information:

• H.Lee Moffitt Cancer Center & Research Institute

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01680965
• Other Study ID Numbers: MCC-17071
• First Posted: Sep 7, 2012
• Last Update Posted: Apr 12, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: Graft vs. Host Disease; GVHD; chronic graft versus host disease (cGVHD); Allogeneic Transplant; Ofatumumab
• Additional relevant MeSH terms: Graft vs Host Disease; Ofatumumab

Study Results

Participant Flow

Arm/Group Title	Phase 1 Cohort 1:Ofatumumab	Phase 1 Cohort 2: Ofatumumab	Phase1 Cohort 3	Phase 2: Maximum Tolerated Dose of Ofatumumab
Arm/Group Description	Phase I Cohort 1: dose of ofatumumab at 300 mg given on day 0 and 14 of study.	Phase I Cohort 2: dose of ofatumumab at 700 mg given on day 0 and 14 of study.	Phase I Cohort 3: dose of ofatumumab at 1000 mg given on day 0 and 14 of study.	Phase II: Maximum tolerated dose (MTD) of Ofatumumab Ofatumumab at 1000 mg on day 0 and 14
Period Title: Overall Study
STARTED	3	3	6	32
COMPLETED	3	3	6	26
NOT COMPLETED	0	0	0	6

Baseline Characteristics

Arm/Group Title	Phase 1 Cohort 1: Ofatumumab	Phase 1 Cohort 2: Ofatumumab	Phase 1 Cohort 3: Ofatumumab	Phase 2: Maximum Tolerated Dose of Ofatumumab	Total
Arm/Group Description	Phase I Cohort 1: dose of ofatumumab at 300 mg given on day 0 and 14 of study.	Phase I Cohort 2: dose of ofatumumab at 700 mg given on day 0 and 14 of study.	Phase I Cohort 3: dose of ofatumumab at 1000 mg given on day 0 and 14 of study.	Phase II: Maximum tolerated dose (MTD) of Ofatumumab Ofatumumab at 1000 mg on day 0 and 14	Total of all reporting groups
Overall Participants	3	3	6	32	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	3 100%	4 66.7%	22 68.8%	32 72.7%
>=65 years	0 0%	0 0%	2 33.3%	10 31.3%	12 27.3%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	2 66.7%	3 50%	10 31.3%	16 36.4%
Male	2 66.7%	1 33.3%	3 50%	22 68.8%	28 63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 33.3%	1 16.7%	3 9.4%	5 11.4%
Not Hispanic or Latino	3 100%	2 66.7%	5 83.3%	29 90.6%	39 88.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 3.1%	1 2.3%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	3 100%	3 100%	6 100%	30 93.8%	42 95.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	1 3.1%	1 2.3%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%	32 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose of Ofatumumab
Description	Maximum Tolerated Dose was determined by increasing doses, beginning at 300 mg on day 0 and day 14, then increasing to 700 mg on day 0 and day 14 and finally 1000 mg on day 0 and day 14.
Time Frame	within 21 days of initiation

Outcome Measure Data

Analysis Population Description

All participants in phase 1 portion of study

Arm/Group Title	Phase 1: All Participants
Arm/Group Description	All participants in phase 1 portion of study who received at least 1 dose of Ofatumumab either at 300 mg, 700 mg or 1000 mg.
Measure Participants	12
Number [mg]	1000

2. Primary Outcome

Title	Participants Response Rates
Description	Overall response rate (ORR) at 6 months following initiation of therapy. ORR is the composite outcome of complete response and partial response
Time Frame	6 months following initiation of Ofatumumab

Outcome Measure Data

Analysis Population Description

Participants enrolled in Phase 2 portion of study

Arm/Group Title	Ofatumumab
Arm/Group Description	Phase I: Escalating dose of ofatumumab Phase II: Maximum tolerated dose (MTD) of Ofatumumab Ofatumumab: Phase I: test an escalating dose of ofatumumab at cohorts of 300 mg, 700 mg, and 1000 mg given on day 0 and 14 of study. Phase II: Ofatumumab MTD on day 0 and 14; patients will be followed for total of 24 months (months 1, 3, 6, 12 after therapy, then at 18 and 24 months following therapy)
Measure Participants	32
Number (95% Confidence Interval) [percentage of participants]	62.5 2083.3%

3. Secondary Outcome

Title	Overall Survival (OS) at 24 Months
Description	Overall Survival is defined as the time period from start of treatment to death.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Participants enrolled in Phase 2 portion of study.

Arm/Group Title	Ofatumumab
Arm/Group Description	Phase I: Escalating dose of ofatumumab Phase II: Maximum tolerated dose (MTD) of Ofatumumab Ofatumumab: Phase I: test an escalating dose of ofatumumab at cohorts of 300 mg, 700 mg, and 1000 mg given on day 0 and 14 of study. Phase II: Ofatumumab MTD on day 0 and 14; patients will be followed for total of 24 months (months 1, 3, 6, 12 after therapy, then at 18 and 24 months following therapy)
Measure Participants	32
Number (95% Confidence Interval) [percentage of participants]	74.4 2480%

Adverse Events

Time Frame	6 years, 6 months
Arm/Group Title	Phase 1 Cohort 1		Phase 1 Cohort 2		Phase 1 Cohort 3		Phase 2: MTD
Arm/Group Description	Phase I Cohort 1: dose of ofatumumab at 300 mg given on day 0 and 14 of study.		Phase I Cohort 2: dose of ofatumumab at 700 mg given on day 0 and 14 of study.		Phase I Cohort 3: dose of ofatumumab at 1000 mg given on day 0 and 14 of study.		Phase II: Maximum tolerated dose (MTD) of Ofatumumab Ofatumumab at 1000 mg on day 0 and 14
All Cause Mortality
	Phase 1 Cohort 1		Phase 1 Cohort 2		Phase 1 Cohort 3		Phase 2: MTD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/3 (33.3%)		3/6 (50%)		9/32 (28.1%)
Serious Adverse Events
	Phase 1 Cohort 1		Phase 1 Cohort 2		Phase 1 Cohort 3		Phase 2: MTD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		4/6 (66.7%)		25/32 (78.1%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Febrile neutropenia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/32 (6.3%)	3
Cardiac disorders
Atrial fibrillation	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Gastrointestinal disorders
Colonic perforation	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Diarrhea	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/32 (0%)	0
Colitis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Gastrointestinal pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Lower gastrointestinal hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
General disorders
Flu like symptoms	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
General disorders and administration site conditions - Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Hepatobiliary disorders
Gallbladder obstruction	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Hepatobiliary disorders - Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Infections and infestations
Infections and infestations - Other	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/32 (3.1%)	2
Lung Infection	1/3 (33.3%)	2	0/3 (0%)	0	0/6 (0%)	0	3/32 (9.4%)	6
Sepsis	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	1/32 (3.1%)	1
Skin Infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Upper respiratory infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Urinary tract infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Catheter related infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Enterocolitis infectious	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Injury, poisoning and procedural complications
Fall	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Investigations
Alanine aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Aspartate aminotrasnferase increased	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Platelet count decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Metabolism and nutrition disorders
Dehydration	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Hypokalemia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Musculoskeletal and connective tissue disorders
Chest wall pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Generalized muscle weakness	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/32 (0%)	0
Musculoskeletal and connective tissue disorder - Other	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/32 (0%)	0
Nervous system disorders
Cognitive disturbance	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Headache	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/32 (0%)	0
Renal and urinary disorders
Renal and urinary disorders -Other	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/32 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	2/32 (6.3%)	2
Respiratory failure	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Wheezing	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
Periorbital edema	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Surgical and medical procedures
Surgical and medical procedures - Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Vascular disorders
Hypotension	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/32 (6.3%)	3
Thromboembolic event	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Phase 1 Cohort 1		Phase 1 Cohort 2		Phase 1 Cohort 3		Phase 2: MTD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		6/6 (100%)		24/32 (75%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	2
Leukocytosis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Cardiac disorders
Atrial fibrilation	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Eye disorders
Blurred vision	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/32 (0%)	0
Gastrointestinal disorders
Colitis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Lower GI hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Stomach cramps	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Upper GI hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Abdominal pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/32 (6.3%)	2
Diarrhea	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	2
Gastrointestinal disorders - Other	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/32 (3.1%)	1
Rectal hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
General disorders
Infusion related reactions	0/3 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	2	8/32 (25%)	10
General disorders and administration site conditions -Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Edema limbs	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/32 (0%)	0
Fatigue	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Infections and infestations
Pneumonia	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	4/32 (12.5%)	5
Mucosal infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Nail infection	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/32 (0%)	0
Skin infection	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	1/32 (3.1%)	1
Upper respiratory infection	1/3 (33.3%)	2	1/3 (33.3%)	1	0/6 (0%)	0	0/32 (0%)	0
Infections and infestations - Other	1/3 (33.3%)	3	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Lung infection	1/3 (33.3%)	2	0/3 (0%)	0	2/6 (33.3%)	3	4/32 (12.5%)	4
Urinary tract infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Device related infection	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Wound infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Bladder infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Injury, poisoning and procedural complications
Fall	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Bruising	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/32 (0%)	0
Investigations
Neutrophil Count decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Platelet count decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	6
Aspartate aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	3/32 (9.4%)	4
Hypomagnesemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Musculoskeletal and connective tissue disorders
Flank pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Chest wall pain	1/3 (33.3%)	2	0/3 (0%)	0	0/6 (0%)	0	0/32 (0%)	0
Musculoskeletal and connective tissue disorders -Other	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/32 (3.1%)	1
Muscle weakness lower limb	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Generalized muscle weakness	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Pain in extremity	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Arthritis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Arthralgia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Nervous system disorders
Extrapyramidal disorder	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Dysgeusia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Facial nerve disorder	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/32 (0%)	0
Peripheral sensory neuropathy	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/32 (0%)	0
Peripheral motor neuropathy	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Psychiatric disorders
Confusion	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Insomnia	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	2/32 (6.3%)	2
Anxiety	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Renal and urinary disorders
Renal and urinary disorders - Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	2
Cough	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Dyspnea	0/3 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	2	0/32 (0%)	0
Respiratory, thoracic and mediastinal disorders -Other	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Surgical and medical procedures
Surgical and medical procedures -Other	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1
Vascular disorders
Hypotension	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/32 (6.3%)	3
Vascular disorders - Other	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/32 (0%)	0
Hypertension	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/32 (3.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.