Trial Outcomes & Findings for Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma (NCT NCT01754402)

Last Updated: 2024-02-20

Results Overview

In the phase I dose escalation portion, patients will be sequentially enrolled in 4 cohorts at dose levels in a standard 3+3 design until the maximum tolerated dose (MTD) is reached. Cohort 1 (bendamustine 120mg/m2 + pomalidomide 3mg); Cohort 2 (bendamustine 120mg/m2 + pomalidomide 4mg); Cohort 3 (bendamustine 150mg/m2 + pomalidomide 4mg); Cohort 4 (bendamustine 180mg/m2 + pomalidomide 4mg) If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

56 participants

Primary outcome timeframe

2 cycles (approximately 2 months)

Results posted on

2024-02-20

Participant Flow

Recruitment began in January 2013. Dose escalation ended in November, 2013. Expansion enrollment began in December, 2013 and ended in September 2016. Patients were recruited from the Bone Marrow Transplant Clinic and Hematologic Malignancies Clinic at Duke University Medical Center.

Nine patients were consented to the study for cohort 1, however, 3 were screen failures. Seven patients were consented to the study for cohort 2, however, 5 were screen failures. Forty patients were consented to the study for the expansion phase, however, 10 were screen failures.

Participant milestones

Participant milestones
Measure	Cohort 1: 120mg Bendamustine + 3mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Cohort 2: 120mg Bendamustine + 4mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Expansion: 120mg Bendamustine + 3mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered at the Maximum Tolerated Dose.
Overall Study STARTED	6	2	30
Overall Study COMPLETED	4	0	26
Overall Study NOT COMPLETED	2	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: 120mg Bendamustine + 3mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Cohort 2: 120mg Bendamustine + 4mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Expansion: 120mg Bendamustine + 3mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered at the Maximum Tolerated Dose.
Overall Study Death	0	0	1
Overall Study Adverse Event	2	2	1
Overall Study Withdrawal by Subject	0	0	1
Overall Study Lack of Efficacy	0	0	1

Baseline Characteristics

Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: 120mg Bendamustine + 3mg Pomalidomide n=6 Participants * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Cohort 2: 120mg Bendamustine + 4mg Pomalidomide n=2 Participants * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Expansion: 120mg Bendamustine + 3mg Pomalidomide n=30 Participants * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered at the Maximum Tolerated Dose.	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants	20 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	16 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	17 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants	17 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	2 Participants n=7 Participants	29 Participants n=5 Participants	37 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	1 Participants n=7 Participants	25 Participants n=5 Participants	32 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	2 participants n=7 Participants	30 participants n=5 Participants	38 participants n=4 Participants

PRIMARY outcome

Timeframe: 2 cycles (approximately 2 months)

Population: All patients enrolled in cohort 1 and 2 evaluable for DLT. Cohorts 3 and 4 were not evaluated due to both patients in Cohort 2 experiencing DLT.

Outcome measures

Outcome measures
Measure	Cohorts 1 and 2 n=8 Participants * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. (Dose escalation) Bendamustine: Bendamustine 120mg/m2 (cohort 1, 2) or 150 mg/m2 (cohort 3), or 180mg/m2 (cohort 4) will be administered intravenously on day 1, every 28 days for 12 cycles. Pomalidomide: Pomalidomide 3mg (cohort 1) or 4mg (cohort 2, 3, 4) will be administered once daily orally (PO) on days 1-21, every 28 days until disease progression or death. Dexamethasone: Dexamethasone will be administered weekly orally or intravenously on days 1, 8,	Cohort 2: 120mg Bendamustine + 4mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Expansion: 120mg Bendamustine + 3mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered at the Maximum Tolerated Dose.
Maximum Tolerated Dose of Pomalidomide and Bendamustine Pomalidomide	3 milligrams	—	—
Maximum Tolerated Dose of Pomalidomide and Bendamustine Bendamustine	120 milligrams	—	—

PRIMARY outcome

Timeframe: 2 cycles (approximately 2 months)

Population: The overall number of participants analyzed reflects those who received at least 2 cycles of treatment. These participants were assessed for response at that time. The data reported indicates how many patients out of each cohort experienced at least a partial response or complete response.

The number of patients achieving a complete response (CR) or partial response (PR). Response is defined by the International Myeloma Working Group as: CR- Negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and \< 5% plasma cells in bone marrow PR- \> 50% reduction of serum M-protein and urine M-protein by \>90% or to \< 200 mg/24 h In addition, if present at baseline, a \> 50% reduction in the size of soft tissue plasmacytomas is also required VGPR - Serum and urine M-protein detectable by immunofixation but n

Outcome measures

Outcome measures
Measure	Cohorts 1 and 2 n=5 Participants * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. (Dose escalation) Bendamustine: Bendamustine 120mg/m2 (cohort 1, 2) or 150 mg/m2 (cohort 3), or 180mg/m2 (cohort 4) will be administered intravenously on day 1, every 28 days for 12 cycles. Pomalidomide: Pomalidomide 3mg (cohort 1) or 4mg (cohort 2, 3, 4) will be administered once daily orally (PO) on days 1-21, every 28 days until disease progression or death. Dexamethasone: Dexamethasone will be administered weekly orally or intravenously on days 1, 8,	Cohort 2: 120mg Bendamustine + 4mg Pomalidomide * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort.	Expansion: 120mg Bendamustine + 3mg Pomalidomide n=27 Participants * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression. Study treatment will be administered at the Maximum Tolerated Dose.
Initial Response Rate Partial Response	1 Participants	—	11 Participants
Initial Response Rate Very Good Partial Response	0 Participants	—	2 Participants
Initial Response Rate Complete Response	0 Participants	—	0 Participants

SECONDARY outcome

Timeframe: 2 years after last dose of study drug

Other events: 2 other events

Deaths: 2 deaths

Expansion: 120mg Bendamustine + 3mg Pomalidomide

Serious events: 17 serious events

Other events: 30 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Additional Information

Cristina Gasparetto, MD

Duke University Medical Center

Phone: 919-668-1017

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1: 120mg Bendamustine + 3mg Pomalidomide n=6 participants at risk * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days	Cohort 2: 120mg Bendamustine + 4mg Pomalidomide n=2 participants at risk * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days	Expansion: 120mg Bendamustine + 3mg Pomalidomide n=30 participants at risk * Pomalidomide: once daily oral (PO) dosing on days 1-21, every 28 days * Bendamustine: once intravenous (IV) dosing on day 1, every 28 days * Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22 every 28 days
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	13.3% 4/30 • Number of events 4 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Cardiac disorders Atrial fibrillation	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Cardiac disorders Chest pain - cardiac	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Cardiac disorders Supraventricular tachycardia	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	16.7% 1/6 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Gastrointestinal disorders Mucositis oral	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Gastrointestinal disorders Vomiting	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
General disorders Death NOS	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
General disorders Fever	33.3% 2/6 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	50.0% 1/2 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	30.0% 9/30 • Number of events 9 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Infections and infestations Bronchial infection	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Infections and infestations Infections and infestations - Other, specify	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	6.7% 2/30 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Infections and infestations Lung infection	66.7% 4/6 • Number of events 5 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	13.3% 4/30 • Number of events 4 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Infections and infestations Urinary tract infection	16.7% 1/6 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Infections and infestations Sepsis	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	10.0% 3/30 • Number of events 3 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Injury, poisoning and procedural complications Fracture	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Injury, poisoning and procedural complications Postoperative hemorrhage	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Nervous system disorders Syncope	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Psychiatric disorders Confusion	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Musculoskeletal and connective tissue disorders Generalized muscle weakness	33.3% 2/6 • Number of events 3 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Psychiatric disorders Psychiatric disorders - Other, specify	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	6.7% 2/30 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	6.7% 2/30 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	6.7% 2/30 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	50.0% 1/2 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/30 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Vascular disorders Hypotension	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	6.7% 2/30 • Number of events 2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole
Vascular disorders Thromboembolic event	0.00% 0/6 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	0.00% 0/2 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole	3.3% 1/30 • Number of events 1 • 30 days past last day of drug, up to 1 year Adverse Events were not collected per cohort, so they are represented as a whole