Dose-finding Study of Empegfilgrastim for Neutropenia Prophylaxis in Patients With Breast Cancer

• Sponsor: Biocad (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01569087
• Collaborator: (none)
• Enrollment: 60
• Locations: 5
• Arms: 3
• Duration (Months): 9.1
• Patients Per Site: 12
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of the study is to compare safety and efficacy of a single dose of empegfilgrastimt a dose of 3 or 6 mg versus daily administration of filgrastim at a dose of 5 μg/kg/day.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Neutropenia	Biological: empegfilrastim; Biological: filgrastim	Phase 2

Detailed Description

BCD-017-2 is an open-label randomized phase II clinical study to compare the incidence of CTCAE grade 3/4 neutropenia after a single administration of recombinant human pegylated filgrastim empegfilgrastim (Extimia®) at a dose of 3 or 6 mg versus daily administration of filgrastim at a dose of 5 μg/kg/day for neutropenia prophylaxis in breast cancer patients receiving myelosuppressive chemotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Randomized Multicenter Open-label Phase II Clinical Study Comparing the Efficacy and Safety of the Single Dose of Extimia® Versus Daily Filgrastim for Neutropenia Prophylaxis in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Empegfilgrastim 3 mg Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy	Biological: empegfilrastim; Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.; Other Names: Extimia BCD-017 metpegfilgrastim pegylated filgrastim peg-GCSF empegfilgrastim
Experimental: Empegfilgrastim 6 mg Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy	Biological: empegfilrastim; Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.; Other Names: Extimia BCD-017 metpegfilgrastim pegylated filgrastim peg-GCSF empegfilgrastim
Active Comparator: Filgrastim Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy	Biological: filgrastim; Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.; Other Names: GCSF

Outcome Measures

Primary Outcome Measures

1. CTCAE Grade 3/4 Neutropenia Incidence [21 days]

Secondary Outcome Measures

1. Mean Duration of CTCAE Grade 4 Neutropenia [21 days]

2. The Duration of Any Grade Neutropenia [21 days]

3. Low Level (Nadir) ANC x 10^9/L [21 days]

4. Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy [21 days]

5. Incidence of Febrile Neutropenia [21 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent form;

• Histologically verified diagnosis of stage IIb/III/IV breast cancer;

• Age of 18-70 years inclusive;

• If the patient had received the chemotherapy for breast cancer, it should be finished 30 days before the beginning of the study;

• ECOG Performance Status of 0, 1 or 2, not increasing within during 2 weeks before randomization;

• ANC level of 1500/μL and more at the beginning of the study

• Platelet count of 100 000/μL and more at the beginning of the study

• Hemoglobin level of 90 g/l and more

• Creatinine level <1.5 mg/dl

• Total bilirubin level <1.5 × the upper limit of normal (ULN)

• ALT and/or AST levels <2.5×ULN (5×ULN for patients with liver metastases);

• Alkaline phosphatase <5×ULN;

• Left ventricular ejection fraction >50% and more;

• If the patient had received adjuvant and/or neoadjuvant therapy, the cumulative dose of anthracyclines should not exceed 500 mg/m2 for doxorubicin or 500 mg/m2 for epirubicin;

• Ability of the participant to follow the protocol requirements, according to the Investigator's opinion;

• Patients of childbearing potential must implement reliable contraceptive measures during the study treatment, starting 4 weeks prior randomization and for 6 months after the last administration of the study drug.

Exclusion Criteria:

• Patient has received two or more chemotherapy regimens for the metastatic breast cancer;

• Documented hypersensitivity to filgrastim, pegfilgrastim, docetaxel, doxorubicin, dexamethasone and/or its excipients, PEGylated drugs, recombinant proteins.

• Pregnancy or breastfeeding;

• Systemic antibiotic therapy within 72 h prior empegfilgrastim/filgrastim administration;

• Concomitant radiotherapy (except selective radiotherapy of bone metastases);

• Surgery, radiotherapy (except selective radiotherapy of bone metastases), administration of any experimental drugs within 30 days prior randomization;

• History of bone marrow/stem cell transplantation;

• Conditions limiting the patient's ability to follow the protocol;

• CTCAE grade 2/4 neuropathy

• HIV, HCV, HBV, T.Pallidum infection(s);

• Acute or active chronic infections.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkhangelsk District Clinical Oncology Dispensary	Arkhangelsk		Russian Federation	163045
2	Perm Region Oncology Dispensary	Perm		Russian Federation	614066
3	N.N.Petrov Oncology Research Center	St.Petersburg		Russian Federation	197758
4	Russian scientific center of radiology and surgery technologies	St.Petersburg		Russian Federation
5	Volgograd District Oncology Dispensary №1	Volgograd		Russian Federation	400138

Sponsors and Collaborators

• Biocad

Investigators

• Study Director: Roman A. Ivanov, MD, PhD, Biocad

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Biocad
• ClinicalTrials.gov Identifier: NCT01569087
• Other Study ID Numbers: BCD-017-2
• First Posted: Apr 2, 2012
• Last Update Posted: Dec 5, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Biocad: empegfilgrastim; pegylated filgrastim; neutropenia; febrile neutropenia; chemotherapy-associated neutropenia; breast cancer; docetaxel; doxorubicin
• Additional relevant MeSH terms: Neutropenia; Lenograstim

Study Results

Participant Flow

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Period Title: Overall Study
STARTED	21	20	19
COMPLETED	20	20	18
NOT COMPLETED	1	0	1

Baseline Characteristics

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim	Total
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.	Total of all reporting groups
Overall Participants	21	20	19	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	21 100%	20 100%	19 100%	60 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	54.0	53.5	48.7	53.5
Gender (Count of Participants)
Female	21 100%	20 100%	19 100%	60 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Russian Federation	21 100%	20 100%	19 100%	60 100%
Duration of a disease (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	0.8	0.6	0.5	0.65
Histologic type of a breast cancer (participants) [Number]
ductal	15 71.4%	11 55%	15 78.9%	41 68.3%
lobular	0 0%	3 15%	0 0%	3 5%
ductal/lobular	1 4.8%	0 0%	0 0%	1 1.7%
medullar	2 9.5%	0 0%	0 0%	2 3.3%
no data	3 14.3%	6 30%	4 21.1%	13 21.7%
Expression of hormone receptors (participants) [Number]
estrogen receptors	4 19%	0 0%	2 10.5%	6 10%
estrogen and progesterone receptors	7 33.3%	10 50%	7 36.8%	24 40%
deficiency estrogen and progesterone receptors	9 42.9%	9 45%	9 47.4%	27 45%
no data	1 4.8%	1 5%	1 5.3%	3 5%
HER2 expression (participants) [Number]
1+	6 28.6%	3 15%	3 15.8%	12 20%
2+	3 14.3%	4 20%	3 15.8%	10 16.7%
3+	6 28.6%	3 15%	8 42.1%	17 28.3%
deficiency HER2 expression	5 23.8%	9 45%	5 26.3%	19 31.7%
no data	1 4.8%	1 5%	0 0%	2 3.3%
History previous therapy of breast cancer (participants) [Number]
yes	5 23.8%	5 25%	4 21.1%	14 23.3%
no	16 76.2%	15 75%	15 78.9%	46 76.7%

Outcome Measures

1. Primary Outcome

Title	CTCAE Grade 3/4 Neutropenia Incidence
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 [expected time of nadir] were excluded from analysis)

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Measure Participants	21	20	18
Number [participants]	18 85.7%	13 65%	11 57.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Empegfilgrastim 3 mg, Empegfilgrastim 6 mg, Filgrastim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Mean Duration of CTCAE Grade 4 Neutropenia
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 [expected time of nadir] were excluded from analysis)

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Measure Participants	21	20	18
Mean (Standard Deviation) [days]	0.43 (0.50)	0.40 (0.49)	0.33 (0.47)

3. Secondary Outcome

Title	The Duration of Any Grade Neutropenia
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 [expected time of nadir] were excluded from analysis)

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Measure Participants	21	20	18
Mean (Standard Deviation) [days]	1.86 (1.39)	1.0 (0.79)	0.78 (0.43)

4. Secondary Outcome

Title	Low Level (Nadir) ANC x 10^9/L
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 [expected time of nadir] were excluded from analysis)

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Measure Participants	21	20	18
Median (Inter-Quartile Range) [cells x 10^9/L]	0.57	0.75	0.82

5. Secondary Outcome

Title	Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 [expected time of nadir] were excluded from analysis)

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Measure Participants	21	20	18
Mean (Standard Deviation) [days]	4.8 (1.64)	3.8 (2.04)	3.00 (1.71)

6. Secondary Outcome

Title	Incidence of Febrile Neutropenia
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 [expected time of nadir] were excluded from analysis)

Arm/Group Title	Empegfilgrastim 3 mg	Empegfilgrastim 6 mg	Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.	Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Measure Participants	21	20	18
Number [participants]	1 4.8%	1 5%	0 0%

Adverse Events

Time Frame	1 month
Arm/Group Title	Empegfilgrastim 3 mg		Empegfilgrastim 6 mg		Filgrastim
Arm/Group Description	Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.		Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.		Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy filgrastim: Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
All Cause Mortality
	Empegfilgrastim 3 mg		Empegfilgrastim 6 mg		Filgrastim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Empegfilgrastim 3 mg		Empegfilgrastim 6 mg		Filgrastim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)		2/19 (10.5%)
Blood and lymphatic system disorders
neutropenia grade 4	0/21 (0%)	0	0/20 (0%)	0	2/19 (10.5%)	2
Other (Not Including Serious) Adverse Events
	Empegfilgrastim 3 mg		Empegfilgrastim 6 mg		Filgrastim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		20/20 (100%)		19/19 (100%)
Blood and lymphatic system disorders
neutropenia grade 3	9/21 (42.9%)	9	6/20 (30%)	6	6/19 (31.6%)	6
neutropenia grade 4	9/21 (42.9%)	9	9/20 (45%)	9	7/19 (36.8%)	7
anemia	12/21 (57.1%)	12	12/20 (60%)	12	15/19 (78.9%)	15
white blood cells decreased	21/21 (100%)	21	19/20 (95%)	19	17/19 (89.5%)	17
Trombocitopenia	11/21 (52.4%)	11	12/20 (60%)	12	6/19 (31.6%)	6
febrile neutropenia	1/21 (4.8%)	1	1/20 (5%)	1	0/19 (0%)	0
Endocrine disorders
hiperglicemia	15/21 (71.4%)	15	16/20 (80%)	16	16/19 (84.2%)	16
General disorders
alopecia	8/21 (38.1%)	8	11/20 (55%)	11	12/19 (63.2%)	12
nousea	3/21 (14.3%)	3	7/20 (35%)	7	5/19 (26.3%)	5
fatigue	7/21 (33.3%)	7	8/20 (40%)	8	7/19 (36.8%)	7
headache	0/21 (0%)	0	1/20 (5%)	1	0/19 (0%)	0
Hepatobiliary disorders
ALT decreased	8/21 (38.1%)	8	6/20 (30%)	6	5/19 (26.3%)	5
Alcaline Phosphotase decreased	2/21 (9.5%)	2	2/20 (10%)	2	6/19 (31.6%)	6
Musculoskeletal and connective tissue disorders
ossalgia	3/21 (14.3%)	3	3/20 (15%)	3	3/19 (15.8%)	3
arthralgia	0/21 (0%)	0	1/20 (5%)	1	0/19 (0%)	0

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.