Neugranin in Breast Cancer Participants Receiving Doxorub... | NCT01126190

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Double-Blind Phase: Pegfilgrastim	Active Comparator	Participants will receive pegfilgrastim 6 milligrams (mg), administered by subcutaneous (SC) injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consists of doxorubicin 60 mg/square meter (m^2) and docetaxel 75 mg/m^2 administered sequentially by intravenous (IV) infusion on Day 1 of treatment for up to four 21-day cycles.	Biological: Pegfilgrastim Drug: Chemotherapy
Double-Blind Phase: Neugranin 40 mg	Experimental	Participants will receive neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consists of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.	Biological: Neugranin Drug: Chemotherapy
Open-Label Phase: Neugranin 40 mg	Experimental	Participants will receive neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consists of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.	Biological: Neugranin Drug: Chemotherapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Neugranin	Biological	Neugranin will be administered per dose and schedule specified in the arm description.	Double-Blind Phase: Neugranin 40 mg Open-Label Phase: Neugranin 40 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1	Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 x 10^9/liter [L]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10^9/L within the cycle.	Cycle 1 (cycle length = 21 days)
Open-Label Phase: Duration of Severe Neutropenia in Cycle 1	Severe neutropenia was defined as Grade 4 neutropenia (ANC <0.5 x 10^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10^9/L within the cycle. There was no planned statistical analysis for the open-label phase arm.	Cycle 1 (cycle length = 21 days)

Secondary Outcomes

Measure	Description	Time Frame
Double-Blind Phase: Number of Participants With Febrile Neutropenia	Febrile neutropenia was defined as an imputed or observed ANC <0.5 x 10^9/L and body temperature >38.5 degrees celsius (°C) occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.	Cycles 1-4 (each cycle = 21 days)

Name	Affiliation	Role
Teva Medical Expert, MD	Teva Branded Pharmaceutical Products R&D, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 3502		Gabrovo		5300	Bulgaria
Teva Investigational Site 3511

PubMed Identifier	Type	Citation	Retractions
24485296	Derived	Volovat C, Gladkov OA, Bondarenko IM, Barash S, Buchner A, Bias P, Adar L, Avisar N. Efficacy and safety of balugrastim compared with pegfilgrastim in patients with breast cancer receiving chemotherapy. Clin Breast Cancer. 2014 Apr;14(2):101-8. doi: 10.1016/j.clbc.2013.10.001. Epub 2013 Oct 25.

ID	Title	Description
FG000	Double-Blind Phase: Pegfilgrastim	Participants received pegfilgrastim 6 milligrams (mg), administered by subcutaneous (SC) injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/square meter (m^2) and docetaxel 75 mg/m^2 administered sequentially by intravenous (IV) infusion on Day 1 of treatment for up to four 21-day cycles.

Arm/Group Information

ID	Title	Description
BG000	Double-Blind Phase: Pegfilgrastim	Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.
BG001	Double-Blind Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.
BG002	Open-Label Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1

Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 x 10^9/liter [L]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10^9/L within the cycle.

Per protocol (PP) population included all data from randomized participants that were obtained prior to experiencing major protocol violations.

Posted

Mean

Standard Deviation

days

Cycle 1 (cycle length = 21 days)

ID	Title	Description
OG000	Double-Blind Phase: Pegfilgrastim	Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.
OG001	Double-Blind Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.

Units	Counts
Participants	OG000148 OG001150

Title

Denominators

Categories

Title	Measurements
	OG0001.0± 1.08 OG0011.1± 1.13

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	For the primary non-inferiority endpoint of cycle 1 DSN, the 95% confidence interval (CI) for difference in DSN was calculated by stratified bootstrap resampling.					Mean Difference (Final Values)	0.1			2-Sided	95	-0.13	0.37					Non-Inferiority	Non-inferiority was demonstrated if the upper endpoint of the CI for the difference in mean DSN was less than or equal to 0.62 days

Secondary

Double-Blind Phase: Number of Participants With Febrile Neutropenia

Febrile neutropenia was defined as an imputed or observed ANC <0.5 x 10^9/L and body temperature >38.5 degrees celsius (°C) occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.

PP population included all data from randomized participants that were obtained prior to experiencing major protocol violations.

Posted

Number

participants

Cycles 1-4 (each cycle = 21 days)

ID	Title	Description
OG000	Double-Blind Phase: Pegfilgrastim	Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.
OG001	Double-Blind Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.

Primary

Open-Label Phase: Duration of Severe Neutropenia in Cycle 1

Severe neutropenia was defined as Grade 4 neutropenia (ANC <0.5 x 10^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10^9/L within the cycle. There was no planned statistical analysis for the open-label phase arm.

PP population included all data from randomized participants that were obtained prior to experiencing major protocol violations.

Posted

Mean

Standard Deviation

days

Cycle 1 (cycle length = 21 days)

ID	Title	Description
OG000	Open-Label Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.

Units	Counts
Participants	OG000

Secondary

Open-Label Phase: Number of Participants With Febrile Neutropenia

Febrile neutropenia was defined as an imputed or observed ANC <0.5 x 10^9/L and body temperature >38.5 °C occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.

PP population included all data from randomized participants that were obtained prior to experiencing major protocol violations.

Posted

Number

participants

Cycles 1-4 (each cycle = 21 days)

ID	Title	Description
OG000	Open-Label Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-Blind Phase: Pegfilgrastim	Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.	0	150	7	150	134	150
EG001	Double-Blind Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.	2	153	6	153	139	153
EG002	Open-Label Phase: Neugranin 40 mg	Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m^2 and docetaxel 75 mg/m^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles.	2	77	6	77	71	77

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG0002 events2 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG0004 events4 affected150 at risk EG0012 events2 affected153 at risk EG0022 events2 affected77 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0012 events2 affected153 at risk EG0020 events0 affected77 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0022 events2 affected77 at risk
Atrial tachycardia	Cardiac disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Cyanosis	Cardiac disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Tachycardia	Cardiac disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Disease progression	General disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Multi-organ failure	General disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Vascular complication associated with device	General disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Acute tonsillitis	Infections and infestations	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Device related infection	Infections and infestations	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Hepatitis B	Infections and infestations	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Subdiaphragmatic abscess	Infections and infestations	MedDRA 14	Systematic Assessment	EG0001 events1 affected150 at risk EG0010 events0 affected153 at risk EG0020 events0 affected77 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0011 events1 affected153 at risk EG0020 events0 affected77 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Hypotension	Vascular disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Shock	Vascular disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 14	Systematic Assessment	EG0000 events0 affected150 at risk EG0010 events0 affected153 at risk EG0021 events1 affected77 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG00034 events10 affected150 at risk EG00168 events12 affected153 at risk EG0026 events5 affected77 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG00073 events22 affected150 at risk EG00192 events26 affected153 at risk EG00263 events19 affected77 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG000176 events40 affected150 at risk EG001164 events45 affected153 at risk EG00246 events16 affected77 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14	Systematic Assessment	EG00033 events10 affected150 at risk EG00160 events21 affected153 at risk EG0024 events2 affected77 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 14	Systematic Assessment	EG00011 events7 affected150 at risk EG0018 events6 affected153 at risk EG0024 events4 affected77 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14	Systematic Assessment	EG00024 events17 affected150 at risk EG00134 events22 affected153 at risk EG0029 events8 affected77 at risk
Nausea	Gastrointestinal disorders	MedDRA 14	Systematic Assessment	EG000146 events62 affected150 at risk EG001144 events56 affected153 at risk EG00256 events26 affected77 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14	Systematic Assessment	EG00012 events9 affected150 at risk EG00115 events11 affected153 at risk EG0027 events3 affected77 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14	Systematic Assessment	EG00018 events15 affected150 at risk EG00126 events16 affected153 at risk EG0025 events5 affected77 at risk
Asthenia	General disorders	MedDRA 14	Systematic Assessment	EG00079 events33 affected150 at risk EG001107 events42 affected153 at risk EG00248 events22 affected77 at risk
Fatigue	General disorders	MedDRA 14	Systematic Assessment	EG00031 events15 affected150 at risk EG00135 events16 affected153 at risk EG00210 events6 affected77 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14	Systematic Assessment	EG00046 events20 affected150 at risk EG00154 events24 affected153 at risk EG00216 events10 affected77 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14	Systematic Assessment	EG00026 events16 affected150 at risk EG00129 events18 affected153 at risk EG00239 events14 affected77 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14	Systematic Assessment	EG0005 events4 affected150 at risk EG00117 events10 affected153 at risk EG00210 events7 affected77 at risk
Headache	Nervous system disorders	MedDRA 14	Systematic Assessment	EG00023 events16 affected150 at risk EG00133 events20 affected153 at risk EG00210 events7 affected77 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 14	Systematic Assessment	EG000135 events114 affected150 at risk EG001153 events124 affected153 at risk EG00276 events60 affected77 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 14	Systematic Assessment	EG00028 events12 affected150 at risk EG00128 events12 affected153 at risk EG0020 events0 affected77 at risk

ID	Term
C000600093	balugrastim
C455861	pegfilgrastim
D004358	Drug Therapy
D004317	Doxorubicin
D000077143	Docetaxel

ID	Term
D013812	Therapeutics
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D004224	Diterpenes
D013729	Terpenes