TN02: New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00100178
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), Juvenile Diabetes Research Foundation (Other), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 126
• Locations: 11
• Arms: 3
• Duration (Months): 47
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective of this study is to identify immune intervention strategies that will preserve residual beta cell function at the onset of type 1 diabetes. Scientific evidence developed over the last 10 - 20 years suggests that type 1 diabetes is a chronic, slowly progressive autoimmune disease and that clinical symptoms do not develop until at least 80% - 90% of beta cell mass has been destroyed as a result of the autoimmune process. It is now recognized that preservation of remaining beta cells is clinically important as the ability to secrete, even small amounts of insulin, can make the disease easier to control and help minimize complications associated with having years of inadequate glycemic control.

This clinical trial is the first in a series of studies to be launched by the TrialNet Study Group to test various interventions for preserving residual beta cell function in new onset type 1 diabetes. Specifically, this study is designed to determine the ability of Mycophenolate Mofetil (MMF/CellCept) used alone, or in combination with Daclizumab (DZB/Zenapax) to see if it is possible to stop the immune system from destroying beta cells in new onset type 1 diabetes patients (within 3 months of diagnosis.)

Researchers have made great strides in understanding how the immune system works and in changing the activity of immune cells with medicines called immunotherapies. Some immunotherapies work by making the immune system less active. Scientists have discovered that key immune cells, called T cells, help to cause type 1 diabetes. These T cells are largely responsible for attacking the beta cells that produce insulin. Doctors have found medicines that slow or suppress the activity of T cells. It is hoped that these immunosuppressive medicines can help treat type 1 diabetes by stopping T cells before they destroy all of the beta cells.

Medicines that make the immune system less active have been developed and studied for other diseases. Mycophenolate mofetil (MMF) and Daclizumab (DZB) are two of these medicines. Their effects on the immune system are well understood. Researchers believe these medicines may lessen the immune system's destruction of beta cells that leads to type 1 diabetes. In addition, researchers hope the effect of these medicines will last longer than other therapies.

The goal of this study is to find out if two medicines are able to stop the ongoing destruction of beta cells which are still functioning at the time type 1 diabetes is diagnosed. The two immunosuppressive medications being tested are Mycophenolate mofetil (MMF/CellCept®) and Daclizumab (DZB/Zenapax®). They work by making the immune system less active. TrialNet researchers hope that these medications will help maintain insulin secretion from remaining beta cells and thus help to maintain better glycemic control. Even if the medications work, study participants will still need to take insulin injections but it may make it easier to control normal blood sugar levels which can help reduce long-term complications of diabetes such as blindness, kidney failure, nerve damage, heart attack and stroke.

The aim is to arrest beta cell destruction in newly diabetic subjects because immune modulation may not work well alone once the autoimmune process has progressed to complete or near complete destruction of beta cells. The study's rationale is to demonstrate a meaningful preservation of islet function with minimal immune system side effects over the 4-year course of this study.

The data from this clinical trial could serve as the basis for a larger trial if the results are sufficiently positive, or they could suggest other combined intervention trials that might achieve either better efficacy or potentially preserve C-peptide without the need for continued immunosuppression.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Mycophenolate mofeteil (MMF); Drug: Daclizumab (DZB); Drug: Placebo control for Mycophenolate mofeteil (MMF); Drug: Placebo control for Daclizumab (DZB)	Phase 2

Detailed Description

Design of Study:

The study is a multi-center, three-arm, randomized, double-masked, placebo-controlled clinical trial. Comparisons will be made among the three groups, which are:

• Mycophenolate mofetil active drug with Daclizumab (DZB) placebo IV

• Mycophenolate mofetil active drug with active Daclizumab IV

• Mycophenolate mofetil placebo with Daclizumab placebo IV

Participants that agree to enroll in the study will be asked to take study medications for two years. MMF is given by mouth twice a day. DZB is given by an intravenous infusion twice, once at the time of enrollment and again two weeks later. Both these medications are approved by the U.S. Food and Drug Administration and are used by people who have received an organ transplant. This study is testing a new use of these medications to preserve insulin secretion by delaying or stopping further destruction of insulin-secreting cells in people with newly diagnosed type 1 diabetes. Both MMF and DZB make the immune system less active. Participants will be monitored closely for any possible side effects that can occur from taking either DZB and/or MMF due to decreased activity of the immune system.

Participants will need to go to the Clinical Center for visits and tests. For the first month participants will come in every week; then participants will come in at month 2 and month 3. After the month 3 visit, visits will occur about every three months. At most visits, blood will be drawn and participants will meet with a study physician to review their overall diabetes management, and be monitored for any possible side-effects from the study medication.

Participants will be asked to do a longer test called a Mixed Meal Tolerance Test (MMTT) at the initial visit and at five additional visits while taking the assigned study medication. The MMTT involves drinking a special drink which has a controlled amount of carbohydrates, protein, and fat to measure residual insulin secretion. The test requires having an IV inserted into the arm and having blood samples taken from the IV over a period of 2 to 4 hours. After completing the two year period of taking the study medication, participants will be asked to return every 3-6 months for an additional 1-2 years to evaluate their ability to secrete insulin after discontinuing the study medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial (Preservation of Pancreatic Production of Insulin Through Immunosuppression-POPPII #1)
• Study Start Date: May 1, 2004
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MMF and DBZ DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and MMF given orally at dose of 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.	Drug: Mycophenolate mofeteil (MMF); Drug: Daclizumab (DZB)
Experimental: MMF Alone MMF given orally at dose of 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.	Drug: Mycophenolate mofeteil (MMF); Drug: Placebo control for Daclizumab (DZB); saline intravenous infusions
Placebo Comparator: Placebo Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.	Drug: Placebo control for Mycophenolate mofeteil (MMF); Placebo pills taken orally; Drug: Placebo control for Daclizumab (DZB); saline intravenous infusions

Outcome Measures

Primary Outcome Measures

1. Mean Stimulated C-peptide Area Under the Curve [2 years]

   The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Potential participants must meet the following inclusion criteria:

• Be within 3-months of diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria

• Be between the ages of 8 and 45 years old

• Must have stimulated C-peptide levels > 0.2 pmol/ml (measured during an MMTT administered no more than one month prior to the date of randomization)

• Must have either detectable anti-GAD, anti-ICA512/IA-2, insulin autoantibodies (unless received insulin therapy for 7 days or more), or islet cell autoantibodies.

[The reason for inclusion of these enrollment criteria is to avoid inclusion of patients with "Type 1B diabetes mellitus", which may not involve the immunologic criteria measured by the assays that will be utilized.]

• If participant has reproductive potential, he or she must be agreeable to an effective form of birth control (unless abstinence is the chosen method).

• If participant is female with reproductive potential, she must be willing to undergo pregnancy testing and to report possible or confirmed pregnancies promptly during the course of the MMF/DZB study.

• Must be willing to comply with intensive diabetes management. The goal of management will be an HbA1c of 7.0% for all participants, regardless of age. Participants will be expected to take a sufficient number of daily insulin shots to meet this goal. Alternatively, participants can use insulin pump therapy. Participants will also be expected to test their blood sugar at least 3-4 times per day. There will be a Certified Diabetes Educator working with study participants to achieve these goals.

Exclusion Criteria:

Potential participants must not meet any of the following exclusion criteria:

• Have any complicating medical issues that would interfere with blood drawing or monitoring.

• Have a Body Mass Index (BMI) that is greater than the 95th percentile for age and gender.

• Have serologic evidence of HIV infection.

• Have serologic evidence of Hepatitis B infection.

• Have serologic evidence of Hepatitis C infection.

• Have abnormal liver function tests.

• Have a history of leukopenia and/or neutropenia.

• Have a history of chronic peptic ulcer disease, erosive esophagitis, chronic inflammatory bowel disease and/or chronic colonic disease.

• Have a positive PPD test result.

• Have had any live vaccinations in the preceding 6 weeks (e.g. MMR-second dose, live flu vaccine, varicella vaccine, live polio vaccine, yellow fever vaccine).

• Resides outside reasonable geographical proximity to the clinic (i.e., residence outside the state in which the Investigator and study reside, residence outside an immediately neighboring state, or residence outside an area that the Investigator considers reasonable). It is left to the Investigator's discretion to decide if a patient's geographical residence is prohibitive to complete study participation.

• Require chronic use of steroids or other immunosuppressive agents for other conditions.

• Be currently pregnant or 3 months postpartum.

• Be currently nursing or within 6 weeks of having completed nursing.

• Anticipate getting pregnant, or fathering a child, during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
2	University of California-San Francisco	San Francisco	California	United States	94143
3	Stanford University	Stanford	California	United States	94305-5208
4	Barbara Davis Center for Childhood Diabetes, University of Colorado	Denver	Colorado	United States	80262
5	University of Florida	Gainesville	Florida	United States	32610
6	Indiana University	Indianapolis	Indiana	United States	46202
7	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
8	University of Minnesota	Minneapolis	Minnesota	United States	55455
9	Columbia University	New York	New York	United States	10032
10	Benaroya Research Institute	Seattle	Washington	United States	98101
11	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Juvenile Diabetes Research Foundation
• National Center for Research Resources (NCRR)

Investigators

• Study Chair: Jay S Skyler, M.D., University of Miami

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• TrialNet Study Group
• American Diabetes Association

Publications

• Brazelton TR, Morris RE. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol. 1996 Oct;8(5):710-20. Review.
• Feutren G, Papoz L, Assan R, Vialettes B, Karsenty G, Vexiau P, Du Rostu H, Rodier M, Sirmai J, Lallemand A, et al. Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet. 1986 Jul 19;2(8499):119-24.
• Kaufman DB, Leventhal JR, Stuart J, Abecassis MM, Fryer JP, Stuart FP. Mycophenolate mofetil and tacrolimus as primary maintenance immunosuppression in simultaneous pancreas-kidney transplantation: initial experience in 50 consecutive cases. Transplantation. 1999 Feb 27;67(4):586-93.
• Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, Lachin JM, Polonsky KS, Pozzilli P, Skyler JS, Steffes MW. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004 Jan;53(1):250-64. Erratum in: Diabetes. 2004 Jul;53(7):1934.
• Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. European Mycophenolate Mofetil Cooperative Study Group. Lancet. 1995 May 27;345(8961):1321-5.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT00100178
• Other Study ID Numbers: TN02 MMF/DZB; U01DK061055; UC4DK097835
• First Posted: Dec 24, 2004
• Last Update Posted: May 5, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): immunosuppressive therapy; Type 1 Diabetes TrialNet; TrialNet; POPPII; POPPII-1
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Mycophenolic Acid; Daclizumab

Study Results

Participant Flow

Recruitment Details	Thirteen Clinical Centers at academic institutions recruited and enrolled 126 subjects ages 8 to 45 years with autoimmune T1D for less than 3 months.
Pre-assignment Detail	Subjects were screened for evidence of autoantibodies and c-peptide >0.2 pmol on a stimulated 2 hr Mixed Meal Tolerance Test to determine eligibility for the study.The MMTT must be conducted at least 21 days from the diagnosis of diabetes and no more than one month (37 days) prior to the date of randomization.

Arm/Group Title	MMF and DZB	MMF Alone	MMF-DZB Placebo Control
Arm/Group Description	DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.	600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.	Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
Period Title: Overall Study
STARTED	41	31	42
COMPLETED	32	21	32
NOT COMPLETED	9	10	10

Baseline Characteristics

Arm/Group Title	MMF and DZB	MMF Alone	MMF-DZB Placebo Control	Total
Arm/Group Description	600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years AND DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later.	600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years AND saline intravenous infusions given at baseline and two weeks later	Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later.	Total of all reporting groups
Overall Participants	41	31	42	114
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18.4 (9.09)	17.1 (6.71)	18.8 (10.44)	18.2 (9.01)
Sex: Female, Male (Count of Participants)
Female	18 43.9%	11 35.5%	17 40.5%	46 40.4%
Male	23 56.1%	20 64.5%	25 59.5%	68 59.6%

Outcome Measures

1. Primary Outcome

Title	Mean Stimulated C-peptide Area Under the Curve
Description	The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Participants who completed a 4-hour mixed meal glucose tolerance test at the two-year visit were included in the analysis

Arm/Group Title	MMF and DZB	Placebo Control	MMF Alone
Arm/Group Description	DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.	Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.	600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
Measure Participants	22	20	18
Geometric Mean (95% Confidence Interval) [pmol/ml]	0.28	0.27	0.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF and DZB, Placebo Control
	Comments	The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	MMF and DZB		MMF Alone		MMF-DZB Placebo Control
Arm/Group Description	600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later .		600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.		Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later.
All Cause Mortality
	MMF and DZB		MMF Alone		MMF-DZB Placebo Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MMF and DZB		MMF Alone		MMF-DZB Placebo Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/41 (36.6%)		5/31 (16.1%)		5/42 (11.9%)
Blood and lymphatic system disorders
Lymphopenia	0/41 (0%)	0	1/31 (3.2%)	1	0/42 (0%)	0
Blood/Bone Marrow Unspecified	3/41 (7.3%)	3	1/31 (3.2%)	1	1/42 (2.4%)	1
Cardiac disorders
Cardiac General - Other	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Eye disorders
Cataract	1/41 (2.4%)	2	0/31 (0%)	0	0/42 (0%)	0
Ocular/Visual - Other	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Gastrointestinal disorders
Diarrhea	1/41 (2.4%)	1	1/31 (3.2%)	1	0/42 (0%)	0
Vomiting	0/41 (0%)	0	0/31 (0%)	0	1/42 (2.4%)	1
Gastrointestinal- Other	0/41 (0%)	0	0/31 (0%)	0	1/42 (2.4%)	1
General disorders
Secondary Malignancy Unspecified	0/41 (0%)	0	1/31 (3.2%)	1	0/42 (0%)	0
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other	0/41 (0%)	0	1/31 (3.2%)	1	0/42 (0%)	0
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Metabolism and nutrition disorders
Amylase	0/41 (0%)	0	1/31 (3.2%)	1	0/42 (0%)	0
Glucose, serum-high (hyperglycemia)	1/41 (2.4%)	1	1/31 (3.2%)	1	2/42 (4.8%)	2
Glucose, serum-low (hypoglycemia)	1/41 (2.4%)	1	0/31 (0%)	0	1/42 (2.4%)	1
Metabolic/Laboratory - Other	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Metabolic/Laboratory Unspecified	2/41 (4.9%)	2	0/31 (0%)	0	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
Fracture	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Nervous system disorders
Seizure	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Psychiatric disorders
Mood alteration	1/41 (2.4%)	2	1/31 (3.2%)	2	0/42 (0%)	0
Reproductive system and breast disorders
Sexual/Reproductive Function - Other	1/41 (2.4%)	1	0/31 (0%)	0	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	MMF and DZB		MMF Alone		MMF-DZB Placebo Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/41 (100%)		31/31 (100%)		41/42 (97.6%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other	4/41 (9.8%)	5	5/31 (16.1%)	10	0/42 (0%)	0
Leukocytes (total WBC)	5/41 (12.2%)	7	4/31 (12.9%)	10	0/42 (0%)	0
Blood/Bone Marrow Unspecified	6/41 (14.6%)	9	7/31 (22.6%)	14	7/42 (16.7%)	13
Lymphatics - Other	4/41 (9.8%)	5	0/31 (0%)	0	0/42 (0%)	0
Lymphopenia	0/41 (0%)	0	2/31 (6.5%)	3	0/42 (0%)	0
Cardiac disorders
Vasovagal episode	0/41 (0%)	0	2/31 (6.5%)	2	0/42 (0%)	0
Endocrine disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis)	0/41 (0%)	0	2/31 (6.5%)	2	0/42 (0%)	0
Gastrointestinal disorders
Dental: periodontal disease	0/41 (0%)	0	2/31 (6.5%)	2	0/42 (0%)	0
Dental: teeth	3/41 (7.3%)	3	4/31 (12.9%)	4	0/42 (0%)	0
Diarrhea	12/41 (29.3%)	14	5/31 (16.1%)	8	12/42 (28.6%)	13
Gastrointestinal - Other	0/41 (0%)	0	3/31 (9.7%)	3	5/42 (11.9%)	6
Nausea	7/41 (17.1%)	11	5/31 (16.1%)	5	6/42 (14.3%)	7
Vomiting	8/41 (19.5%)	11	7/31 (22.6%)	8	6/42 (14.3%)	6
General disorders
Fatigue (asthenia, lethargy, malaise)	0/41 (0%)	0	2/31 (6.5%)	2	0/42 (0%)	0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	4/41 (9.8%)	4	3/31 (9.7%)	4	0/42 (0%)	0
Other AE Unspecified	5/41 (12.2%)	6	5/31 (16.1%)	11	5/42 (11.9%)	8
Pain	10/41 (24.4%)	11	6/31 (19.4%)	18	8/42 (19%)	11
Flu-like syndrome	0/41 (0%)	0	0/31 (0%)	0	4/42 (9.5%)	5
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	0/41 (0%)	0	2/31 (6.5%)	3	0/42 (0%)	0
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	6/41 (14.6%)	7	0/31 (0%)	0	3/42 (7.1%)	3
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e	5/41 (12.2%)	6	4/31 (12.9%)	4	5/42 (11.9%)	6
Infection - Other	5/41 (12.2%)	5	0/31 (0%)	0	0/42 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils	10/41 (24.4%)	18	6/31 (19.4%)	15	7/42 (16.7%)	8
Infection with unknown ANC	36/41 (87.8%)	106	27/31 (87.1%)	61	34/42 (81%)	94
Infection Unspecified	10/41 (24.4%)	23	2/31 (6.5%)	11	6/42 (14.3%)	8
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)	0/41 (0%)	0	3/31 (9.7%)	5	0/42 (0%)	0
Glucose, serum-low (hypoglycemia)	13/41 (31.7%)	24	9/31 (29%)	21	10/42 (23.8%)	26
Metabolic/Laboratory Unspecified	8/41 (19.5%)	10	0/31 (0%)	0	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
Fracture	3/41 (7.3%)	3	0/31 (0%)	0	7/42 (16.7%)	8
Musculoskeletal/Soft Tissue - Other	8/41 (19.5%)	13	3/31 (9.7%)	5	9/42 (21.4%)	10
Nervous system disorders
Dizziness	0/41 (0%)	0	2/31 (6.5%)	2	0/42 (0%)	0
Psychiatric disorders
Mood alteration	0/41 (0%)	0	2/31 (6.5%)	2	3/42 (7.1%)	3
Reproductive system and breast disorders
Irregular menses (change from baseline)	3/41 (7.3%)	4	0/31 (0%)	0	0/42 (0%)	0
Sexual/Reproductive Function - Other	0/41 (0%)	0	0/31 (0%)	0	3/42 (7.1%)	3
Respiratory, thoracic and mediastinal disorders
Cough	11/41 (26.8%)	14	2/31 (6.5%)	2	4/42 (9.5%)	5
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other	4/41 (9.8%)	5	6/31 (19.4%)	7	0/42 (0%)	0
Rash/desquamation	11/41 (26.8%)	14	3/31 (9.7%)	5	5/42 (11.9%)	6
Rash: acne/acneiform	3/41 (7.3%)	4	4/31 (12.9%)	4	0/42 (0%)	0
Vascular disorders
Hemorrhage, pulmonary/upper respiratory	0/41 (0%)	0	3/31 (9.7%)	5	0/42 (0%)	0

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.