Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00117507
• Collaborator: (none)

Study Details

Study Description

Brief Summary

Thirty patients were to be enrolled and 24 patients were actually enrolled into this open-label, single-arm trial designed to assess the safety and tolerability of oral deferasirox in adult transfusion dependent myelodysplastic syndrome (MDS) patients with iron overload. Patients enrolled in this study had low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria. All patients initiated treatment with 20mg/kg/day deferasirox.

Deferasirox were administered orally once per day for 12 months.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes; Iron Overload	Drug: Deferasirox	Phase 4

Detailed Description

Patients were screened for eligibility to determine if they meet all inclusion/exclusion criteria. The screening period were up to 4 weeks. Patient's baseline LIC will be determined non-invasively by means of MRI R2 analysis. In addition, blood and urine samples will be taken for the determination of baseline safety data.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-Risk and INT-1 Myelodysplastic Patients
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox Participants received deferasirox 20mg/kg/day OD for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.	Drug: Deferasirox; Other Names: Chelator Iron chelator

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events and Serious Adverse Events [Up To Week 52]

   An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Any sign or symptom that occured from first dose of study treatment until end of study treatment.

Secondary Outcome Measures

1. Absolute Change in Serum Ferritin From Baseline to Week 52 [Baseline to Week 52]

   Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670).

2. Absolute Change in Liver Iron Concentration (LIC) From Baseline to End of Study [Baseline to Week 52]

   LIC was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2).

3. To Evaluate Change in Transfusion Requirements [Baseline to Week 52]

   Change in transfusion requirements from baseline.

4. Absolute Change in Serum Erythropoietin [Baseline to Week 52]

   Absolute Change in Serum Erythropoietin from baseline.

5. Absolute Change in Urinary Hepcidin [Baseline to Week 52]

   Absolute Change in Urinary Hepcidin from baseline

6. Absolute Change in Transferrin Saturation [Baseline to Week 52]

   Transferrin Saturation was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2)

7. Labile Plasma Iron (LPI) [Baseline to Week 52]

   LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The outcome was reported as LPI Unit, where, 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female patients with low or intermediate (INT-1) risk MDS, determined via IPSS criteria, with transfusional iron overload. NOTE: Bone marrow morphology and cytogenetic studies completed within 3 months prior to screening can be used if the patient has been hematologically stable. Every attempt to obtain cytogenetics studies should be made; however, if there is culture failure, repeat marrow aspiration will not be mandated. In this case, RAEB with less than 11% marrow blasts will be accepted.

• Patients on chelation therapy at the time of screening required a 1-day wash out prior to the first dose of study drug.

• Age: greater than or equal to 18 years

• Serum ferritin:

• For entry into the screening period: serum ferritin greater than or equal to 1000 µg/mL on at least two occasions, at least two weeks apart, during the prior year. Samples must be obtained in the absence of concomitant infection;

• For enrollment into the study: serum ferritin greater than or equal to 1000 µg/mL at screening (via the central lab) obtained in the absence of concomitant infection

• A lifetime minimum of 20 previous packed red cell transfusions

• Life expectancy greater than or equal to 6 months

• Women must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined by amenorrhea for at least 12 months).

• Able to provide written informed consent

Exclusion Criteria:

• Serum creatinine greater than 2 × upper limit of normal (ULN)

• ALT or AST greater than 5 × ULN.

• Clinical or laboratory evidence of active hepatitis B or hepatitis C (HBsAg in the absence of HBsAb -OR- HCV Ab positive with HCV RNA positive and ALT above the normal range)

• Significant proteinuria as indicated by a urinary protein/creatinine ratio greater than 0.5 mg/mg in a non-first void urine sample during screening (or alternatively in two of three samples obtained for screening)

• History of HIV positive test result (ELISA or Western blot)

• ECOG performance status greater than 2

• Uncontrolled systemic hypertension

• Unstable cardiac disease not controlled by standard medical therapy

• Third degree atrioventricular (AV) block or QT interval prolongation above the normal range

• History of clinically relevant ocular toxicity related to iron chelation

• Pregnancy or breast feeding

• Treatment with a systemic investigational drug within the past 4 weeks or a topical investigational drug within the past 7 days.

• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

• inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;

• major gastrointestinal tract surgery, such as gastrectomy, gastroenterostomy, or bowel resection;

• pancreatic injury or pancreatitis or indications of impaired pancreatic function/injury, as indicated by abnormal lipase or amylase;

• urinary obstruction or difficulty in voiding.

• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305-5821
2	Karmanos Cancer Center	Detroit	Michigan	United States	48201
3	MD Anderson Cancer Center	Houston	Texas	United States	77030-4009

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Results for CICL670AUS02 from the Novartis Clinical Trials website
• Publication (Embasse # 2010614101)
• Results for CICL670AUS02 from the Novartis Clinical Trials website

Publications

• Greenberg PL, Koller CA, Cabantchik ZI, Warsi G, Glynos T, Paley C, Schiffer C. Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes. Leuk Res. 2010 Dec;34(12):1560-5. doi: 10.1016/j.leukres.2010.06.013. Epub 2010 Jul 8.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00117507
• Other Study ID Numbers: CICL670AUS02
• First Posted: Jul 7, 2005
• Last Update Posted: Jun 24, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Novartis Pharmaceuticals: MDS; Myelodysplastic Syndrome; ICL-670; ICL-670 and Myelodysplastic Syndrome
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Iron Overload; Syndrome; Deferasirox; Chelating Agents

Study Results

Participant Flow

Recruitment Details	The study enrolled participants at 3 centers in United States.
Pre-assignment Detail	A total 24 participants were enrolled in the study of which 9 participants completed the study and 15 participants discontinued from the study.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD (Once Daily) per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Period Title: Overall Study
STARTED	24
COMPLETED	9
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.6 (8.58)
Sex: Female, Male (Count of Participants)
Female	8 33.3%
Male	16 66.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events
Description	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Any sign or symptom that occured from first dose of study treatment until end of study treatment.
Time Frame	Up To Week 52

Outcome Measure Data

Analysis Population Description

The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months.
Measure Participants	24
Adverse events	24 100%
Serious adverse events	11 45.8%

2. Secondary Outcome

Title	Absolute Change in Serum Ferritin From Baseline to Week 52
Description	Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670).
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all participants who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months.
Measure Participants	24
Baseline	3847.6 (2854.54)
Week 52/EOS (end of study)	-729.8 (2749.35)

3. Secondary Outcome

Title	Absolute Change in Liver Iron Concentration (LIC) From Baseline to End of Study
Description	LIC was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2).
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all patients who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	24
Baseline	20.64 (9.747)
Week 52/EOS	-4.50 (12.995)

4. Secondary Outcome

Title	To Evaluate Change in Transfusion Requirements
Description	Change in transfusion requirements from baseline.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all participants who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	24
Number of Transfusions per Patient	15.5 (9.46)
Number of Units of Blood Transfused per Patient	34.0 (24.65)

5. Secondary Outcome

Title	Absolute Change in Serum Erythropoietin
Description	Absolute Change in Serum Erythropoietin from baseline.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all participants who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	24
Baseline	646.50
Week 52/EOS	-79.00

6. Secondary Outcome

Title	Absolute Change in Urinary Hepcidin
Description	Absolute Change in Urinary Hepcidin from baseline
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all participants who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	17
Baseline	327.63
Week 52/EOS	67.32

7. Secondary Outcome

Title	Absolute Change in Transferrin Saturation
Description	Transferrin Saturation was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2)
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all participants who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	24
Baseline	59.3 (7.24)
Week 52/EOS (Change from baseline)	8.6 (21.19)

8. Secondary Outcome

Title	Labile Plasma Iron (LPI)
Description	LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The outcome was reported as LPI Unit, where, 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all patients who were registered in the study, whether or not they received treatment.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Measure Participants	24
Baseline	0.70 (0.638)
Week 52/EOS	0.22 (0.460)

Adverse Events

Time Frame	Adverse events were collected From Start of the Study up to EOS (Week 52). The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
Arm/Group Title	Deferasirox
Arm/Group Description	Participants received deferasirox 20mg/kg/day OD per day for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
All Cause Mortality
	Deferasirox
	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)
Serious Adverse Events
	Deferasirox
	Affected / at Risk (%)	# Events
Total	11/24 (45.8%)
Blood and lymphatic system disorders
Splenic infarction	1/24 (4.2%)
Cardiac disorders
Arrhythmia	1/24 (4.2%)
Cardiac failure congestive	2/24 (8.3%)
Left ventricular hypertrophy	1/24 (4.2%)
Gastrointestinal disorders
Ascites	1/24 (4.2%)
Diarrhoea	1/24 (4.2%)
General disorders
Asthenia	1/24 (4.2%)
Chest pain	2/24 (8.3%)
Chills	1/24 (4.2%)
Concomitant disease progression	1/24 (4.2%)
Oedema	1/24 (4.2%)
Oedema peripheral	1/24 (4.2%)
Pyrexia	4/24 (16.7%)
Hepatobiliary disorders
Cholecystitis acute	1/24 (4.2%)
Infections and infestations
Bronchitis	1/24 (4.2%)
Pneumonia	1/24 (4.2%)
Urinary tract infection	2/24 (8.3%)
Injury, poisoning and procedural complications
Joint dislocation	1/24 (4.2%)
Skull fracture	1/24 (4.2%)
Subdural haemorrhage	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/24 (4.2%)
Pain in extremity	1/24 (4.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/24 (4.2%)
Nervous system disorders
Depressed level of consciousness	1/24 (4.2%)
Syncope	1/24 (4.2%)
Renal and urinary disorders
Nephrolithiasis	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/24 (8.3%)
Orthopnoea	1/24 (4.2%)
Pleural effusion	1/24 (4.2%)
Respiratory arrest	1/24 (4.2%)
Other (Not Including Serious) Adverse Events
	Deferasirox
	Affected / at Risk (%)	# Events
Total	23/24 (95.8%)
Blood and lymphatic system disorders
Leukocytosis	1/24 (4.2%)
Monocytosis	1/24 (4.2%)
Splenic infarction	1/24 (4.2%)
Splenomegaly	2/24 (8.3%)
Thrombocytopenia	1/24 (4.2%)
Cardiac disorders
Dilatation atrial	1/24 (4.2%)
Dilatation ventricular	1/24 (4.2%)
Palpitations	2/24 (8.3%)
Pericardial effusion	1/24 (4.2%)
Sinus tachycardia	1/24 (4.2%)
Tachycardia	2/24 (8.3%)
Ventricular tachycardia	1/24 (4.2%)
Ear and labyrinth disorders
Vertigo	1/24 (4.2%)
Eye disorders
Conjunctival discolouration	1/24 (4.2%)
Conjunctivitis	1/24 (4.2%)
Gastrointestinal disorders
Abdominal distension	2/24 (8.3%)
Abdominal pain	9/24 (37.5%)
Abdominal pain upper	3/24 (12.5%)
Constipation	4/24 (16.7%)
Diarrhoea	15/24 (62.5%)
Flatulence	1/24 (4.2%)
Frequent bowel movements	1/24 (4.2%)
Gastrooesophageal reflux disease	1/24 (4.2%)
Haemorrhoidal haemorrhage	1/24 (4.2%)
Nausea	11/24 (45.8%)
Odynophagia	1/24 (4.2%)
Rectal haemorrhage	1/24 (4.2%)
Retching	1/24 (4.2%)
Stomach discomfort	1/24 (4.2%)
Vomiting	4/24 (16.7%)
General disorders
Asthenia	2/24 (8.3%)
Chest pain	1/24 (4.2%)
Chills	1/24 (4.2%)
Concomitant disease progression	1/24 (4.2%)
Fatigue	2/24 (8.3%)
Feeling cold	1/24 (4.2%)
Malaise	1/24 (4.2%)
Oedema	3/24 (12.5%)
Oedema peripheral	6/24 (25%)
Pain	1/24 (4.2%)
Pyrexia	3/24 (12.5%)
Hepatobiliary disorders
Hepatomegaly	3/24 (12.5%)
Jaundice	1/24 (4.2%)
Infections and infestations
Bronchitis	3/24 (12.5%)
Catheter related infection	1/24 (4.2%)
Cellulitis	1/24 (4.2%)
Gastroenteritis viral	1/24 (4.2%)
Oral herpes	1/24 (4.2%)
Pneumonia	1/24 (4.2%)
Sinusitis	1/24 (4.2%)
Tooth infection	1/24 (4.2%)
Upper respiratory tract infection	4/24 (16.7%)
Urinary tract infection	1/24 (4.2%)
Injury, poisoning and procedural complications
Contusion	4/24 (16.7%)
Excoriation	1/24 (4.2%)
Lower limb fracture	1/24 (4.2%)
Lumbar vertebral fracture	1/24 (4.2%)
Upper limb fracture	1/24 (4.2%)
Wound	1/24 (4.2%)
Investigations
Alanine aminotransferase increased	1/24 (4.2%)
Aspartate aminotransferase increased	1/24 (4.2%)
Blood bilirubin increased	1/24 (4.2%)
Blood creatinine increased	1/24 (4.2%)
Breath sounds abnormal	1/24 (4.2%)
Haemoglobin decreased	1/24 (4.2%)
Heart rate irregular	1/24 (4.2%)
Lipase increased	1/24 (4.2%)
Weight decreased	6/24 (25%)
Weight increased	1/24 (4.2%)
Metabolism and nutrition disorders
Anorexia	2/24 (8.3%)
Decreased appetite	1/24 (4.2%)
Dehydration	1/24 (4.2%)
Fluid retention	1/24 (4.2%)
Gout	1/24 (4.2%)
Hypercreatininaemia	3/24 (12.5%)
Hypokalaemia	1/24 (4.2%)
Hypomagnesaemia	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/24 (4.2%)
Back pain	2/24 (8.3%)
Bone pain	1/24 (4.2%)
Groin pain	1/24 (4.2%)
Joint effusion	1/24 (4.2%)
Muscle atrophy	1/24 (4.2%)
Muscle spasms	2/24 (8.3%)
Osteoporosis	1/24 (4.2%)
Temporomandibular joint syndrome	1/24 (4.2%)
Nervous system disorders
Headache	3/24 (12.5%)
Migraine	1/24 (4.2%)
Sciatica	1/24 (4.2%)
Syncope	1/24 (4.2%)
Vocal cord paralysis	1/24 (4.2%)
Psychiatric disorders
Confusional state	1/24 (4.2%)
Depression	2/24 (8.3%)
Insomnia	1/24 (4.2%)
Restlessness	1/24 (4.2%)
Renal and urinary disorders
Dysuria	1/24 (4.2%)
Incontinence	1/24 (4.2%)
Micturition urgency	1/24 (4.2%)
Pollakiuria	2/24 (8.3%)
Renal failure	2/24 (8.3%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/24 (4.2%)
Cough	5/24 (20.8%)
Dysphonia	2/24 (8.3%)
Dyspnoea	5/24 (20.8%)
Dyspnoea exertional	1/24 (4.2%)
Epistaxis	1/24 (4.2%)
Lung infiltration	1/24 (4.2%)
Nasal congestion	1/24 (4.2%)
Pharyngolaryngeal pain	1/24 (4.2%)
Postnasal drip	1/24 (4.2%)
Rales	3/24 (12.5%)
Rhinorrhoea	1/24 (4.2%)
Sinus congestion	1/24 (4.2%)
Wheezing	1/24 (4.2%)
Skin and subcutaneous tissue disorders
Dry skin	2/24 (8.3%)
Ecchymosis	3/24 (12.5%)
Hyperhidrosis	1/24 (4.2%)
Increased tendency to bruise	1/24 (4.2%)
Night sweats	1/24 (4.2%)
Periorbital oedema	1/24 (4.2%)
Petechiae	1/24 (4.2%)
Pruritus	2/24 (8.3%)
Purpura	1/24 (4.2%)
Rash	4/24 (16.7%)
Rash macular	1/24 (4.2%)
Skin exfoliation	1/24 (4.2%)
Skin lesion	1/24 (4.2%)
Vascular disorders
Hypotension	1/24 (4.2%)
Pallor	2/24 (8.3%)

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.