Trial Outcomes & Findings for Balugrastim (Neugranin) in Breast Cancer Participants Receiving Doxorubicin/Docetaxel (NCT NCT00837265)

Last Updated: 2024-04-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

334 participants

Primary outcome timeframe

Cycle 1 (cycle length = 21 days)

Results posted on

2024-04-03

Participant Flow

Participant milestones

Participant milestones
Measure	Pilot Phase: Balugrastim Low Dose Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot 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).	Main Phase: Balugrastim Medium Dose Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main 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).
Pilot Phase STARTED	11	21	20	26	0	0	0
Pilot Phase Modified Intent-to-treat (mITT) Population	10	21	20	25	0	0	0
Pilot Phase COMPLETED	8	18	17	22	0	0	0
Pilot Phase NOT COMPLETED	3	3	3	4	0	0	0
Main Phase STARTED	0	0	0	0	86	84	86
Main Phase Received at Least 1 Dose of Study Drug	0	0	0	0	85	84	86
Main Phase COMPLETED	0	0	0	0	76	79	83
Main Phase NOT COMPLETED	0	0	0	0	10	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Pilot Phase: Balugrastim Low Dose Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot 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).	Main Phase: Balugrastim Medium Dose Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main 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).
Pilot Phase Withdrawal by Subject	0	2	3	2	0	0	0
Pilot Phase Decision of the investigator	2	1	0	0	0	0	0
Pilot Phase Adverse Event	1	0	0	0	0	0	0
Pilot Phase Disease progression	0	0	0	1	0	0	0
Pilot Phase Participant left the city	0	0	0	1	0	0	0
Main Phase Withdrawal by Subject	0	0	0	0	4	2	1
Main Phase Decision of the investigator	0	0	0	0	0	2	1
Main Phase Adverse Event	0	0	0	0	0	1	0
Main Phase Death	0	0	0	0	2	0	1
Main Phase Lost to Follow-up	0	0	0	0	1	0	0
Main Phase Principal investigator resignation	0	0	0	0	2	0	0
Main Phase Participant's personal reason	0	0	0	0	1	0	0

Baseline Characteristics

Balugrastim (Neugranin) in Breast Cancer Participants Receiving Doxorubicin/Docetaxel

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pilot Phase: Balugrastim Low Dose n=10 Participants Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose n=21 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose n=20 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Pegfilgrastim n=25 Participants 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).	Main Phase: Balugrastim Medium Dose n=85 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose n=84 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Pegfilgrastim n=86 Participants 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).	Total n=331 Participants Total of all reporting groups
Age, Continuous	56.90 years STANDARD_DEVIATION 9.46 • n=5 Participants	51.38 years STANDARD_DEVIATION 10.27 • n=7 Participants	53.75 years STANDARD_DEVIATION 9.52 • n=5 Participants	52.84 years STANDARD_DEVIATION 10.36 • n=4 Participants	49.19 years STANDARD_DEVIATION 9.87 • n=21 Participants	49.82 years STANDARD_DEVIATION 9.55 • n=8 Participants	50.26 years STANDARD_DEVIATION 9.09 • n=8 Participants	50.55 years STANDARD_DEVIATION 9.68 • n=24 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	25 Participants n=4 Participants	85 Participants n=21 Participants	83 Participants n=8 Participants	86 Participants n=8 Participants	330 Participants n=24 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Race · Caucasian	10 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	25 Participants n=4 Participants	85 Participants n=21 Participants	84 Participants n=8 Participants	86 Participants n=8 Participants	331 Participants n=24 Participants

PRIMARY outcome

Timeframe: Cycle 1 (cycle length = 21 days)

Population: mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Pilot Phase: Balugrastim Low Dose n=10 Participants Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose n=21 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose n=20 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Pegfilgrastim n=25 Participants 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).	Main Phase: Balugrastim Medium Dose n=84 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose n=84 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Pegfilgrastim n=86 Participants 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).
Duration of Severe Neutropenia in Cycle 1	0.9 days Standard Deviation 1.37	1.6 days Standard Deviation 1.83	1.1 days Standard Deviation 1.48	0.9 days Standard Deviation 1.13	1.0 days Standard Deviation 1.09	1.3 days Standard Deviation 1.22	1.2 days Standard Deviation 1.34

SECONDARY outcome

Timeframe: Cycles 1 to 4 (each cycle length = 21 days)

Population: mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug.

Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and oral temperature ≥38.2 degrees celsius (°C) occurring on the same day. Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.

Outcome measures

Outcome measures
Measure	Pilot Phase: Balugrastim Low Dose n=10 Participants Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose n=21 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose n=20 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Pegfilgrastim n=25 Participants 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).	Main Phase: Balugrastim Medium Dose n=85 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose n=84 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Pegfilgrastim n=86 Participants 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).
Number of Participants With Febrile Neutropenia	2 Participants	3 Participants	2 Participants	2 Participants	4 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Cycles 2, 3, and 4 (each cycle length = 21 days)

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.

Outcome measures

Outcome measures
Measure	Pilot Phase: Balugrastim Low Dose n=9 Participants Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose n=21 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose n=19 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Pegfilgrastim n=24 Participants 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).	Main Phase: Balugrastim Medium Dose n=83 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose n=84 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Pegfilgrastim n=84 Participants 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).
Duration of Severe Neutropenia in Cycles 2, 3, and 4 Cycle 2	0.0 days Standard Deviation 0.00	0.8 days Standard Deviation 1.22	0.4 days Standard Deviation 0.68	0.5 days Standard Deviation 0.88	0.5 days Standard Deviation 0.80	0.4 days Standard Deviation 0.80	0.5 days Standard Deviation 0.94
Duration of Severe Neutropenia in Cycles 2, 3, and 4 Cycle 3	0.5 days Standard Deviation 1.07	0.7 days Standard Deviation 0.92	0.6 days Standard Deviation 1.24	0.3 days Standard Deviation 0.61	0.4 days Standard Deviation 0.78	0.5 days Standard Deviation 1.00	0.4 days Standard Deviation 0.71
Duration of Severe Neutropenia in Cycles 2, 3, and 4 Cycle 4	0.9 days Standard Deviation 0.99	0.3 days Standard Deviation 0.77	0.1 days Standard Deviation 0.49	0.7 days Standard Deviation 1.25	0.4 days Standard Deviation 0.79	0.6 days Standard Deviation 1.06	0.6 days Standard Deviation 1.03

SECONDARY outcome

Timeframe: Cycles 1, 2, 3, and 4

Time to ANC recovery was defined as the time from the nadir ANC to an ANC ≥1.5 x 10\^9/L and was calculated for participants with ANC \<1.5 x 10\^9/L after the beginning of a chemotherapy cycle. Time to ANC recovery was calculated by cycle as the number of days from the nadir (the lowest ANC during a chemotherapy cycle) until a participant reached an ANC \>1.5 x 10\^9/L.

Outcome measures

Outcome measures
Measure	Pilot Phase: Balugrastim Low Dose n=10 Participants Participants received balugrastim low dose 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).	Pilot Phase: Balugrastim Medium Dose n=21 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Balugrastim High Dose n=16 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pilot Phase: Pegfilgrastim n=22 Participants 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).	Main Phase: Balugrastim Medium Dose n=71 Participants Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Balugrastim High Dose n=73 Participants Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Main Phase: Pegfilgrastim n=72 Participants 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).
Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 Cycle 1	3.1 days Standard Deviation 2.38	2.6 days Standard Deviation 1.78	2.0 days Standard Deviation 1.26	2.4 days Standard Deviation 1.59	2.0 days Standard Deviation 0.94	2.1 days Standard Deviation 1.03	2.6 days Standard Deviation 1.23
Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 Cycle 2	1.3 days Standard Deviation 0.58	2.1 days Standard Deviation 1.21	1.9 days Standard Deviation 0.79	1.9 days Standard Deviation 1.20	1.8 days Standard Deviation 0.80	1.8 days Standard Deviation 1.11	2.1 days Standard Deviation 1.24
Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 Cycle 3	2.1 days Standard Deviation 1.46	2.0 days Standard Deviation 1.00	2.2 days Standard Deviation 1.39	1.9 days Standard Deviation 1.06	1.9 days Standard Deviation 1.08	2.2 days Standard Deviation 1.33	1.8 days Standard Deviation 0.79
Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 Cycle 4	2.9 days Standard Deviation 1.68	1.8 days Standard Deviation 0.83	1.3 days Standard Deviation 0.49	2.3 days Standard Deviation 1.49	1.9 days Standard Deviation 0.85	2.1 days Standard Deviation 1.16	2.1 days Standard Deviation 1.27

Adverse Events

Balugrastim Low Dose

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Balugrastim Medium Dose

Serious events: 11 serious events

Other events: 102 other events

Deaths: 0 deaths

Balugrastim High Dose

Serious events: 9 serious events

Other events: 100 other events

Deaths: 0 deaths

Pegfilgrastim

Serious events: 10 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Balugrastim Low Dose n=10 participants at risk Participants received balugrastim low dose 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).	Balugrastim Medium Dose n=105 participants at risk Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Balugrastim High Dose n=104 participants at risk Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).	Pegfilgrastim n=112 participants at risk 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).
Blood and lymphatic system disorders Anaemia	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.96% 1/104 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Blood and lymphatic system disorders Febrile neutropenia	20.0% 2/10 • Number of events 3 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	6.7% 7/105 • Number of events 7 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	6.7% 7/104 • Number of events 7 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	4.5% 5/112 • Number of events 6 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Blood and lymphatic system disorders Neutropenia	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.95% 1/105 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
General disorders Pyrexia	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.89% 1/112 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Infections and infestations Abdominal wall abscess	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.89% 1/112 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Infections and infestations Bronchitis	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.96% 1/104 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Infections and infestations Pneumonia	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.89% 1/112 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Infections and infestations Upper respiratory tract infection	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.89% 1/112 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Metabolism and nutrition disorders Diabetic foot	10.0% 1/10 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.89% 1/112 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.95% 1/105 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Psychiatric disorders Cyclothymic disorder	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.95% 1/105 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Renal and urinary disorders Calculus ureteric	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.95% 1/105 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/112 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/10 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/105 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.00% 0/104 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.	0.89% 1/112 • Number of events 1 • From the start of study drug administration through 30 days following the final dose of study drug (up to 114 days) mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER