Trial Outcomes & Findings for Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study (NCT NCT01054196)

NCT ID: NCT01054196

Last Updated: 2025-05-13

Results Overview

The primary endpoint for the phase 1 portion of this study is to determine the maximum tolerated dose of lenalidomide that can be added to melphalan.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE1/PHASE2
• Target enrollment: 52 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2025-05-13

Participant Flow

Participant milestones

Measure	Phase 1 Dose Level 1 Oral lenalidomide 25mg twice daily x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 2 Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 Expansion Early studies noted a dose response relationship and found myelosuppression to be the dose limiting toxicity. In this Phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT shown no DLT noted up to 350mg PO daily of LEN. In Phase 2, HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Overall Study STARTED	2	4	3	4	6	3	30
Overall Study COMPLETED	2	4	3	3	6	3	29
Overall Study NOT COMPLETED	0	0	0	1	0	0	1

Reasons for withdrawal

Measure	Phase 1 Dose Level 1 Oral lenalidomide 25mg twice daily x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 2 Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 Expansion Early studies noted a dose response relationship and found myelosuppression to be the dose limiting toxicity. In this Phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT shown no DLT noted up to 350mg PO daily of LEN. In Phase 2, HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Overall Study Physician Decision	0	0	0	1	0	0	1

Baseline Characteristics

Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study

Baseline characteristics by cohort

Measure	Phase 1 Dose Level 1 n=2 Participants Oral lenalidomide 25mg twice daily x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 2 n=4 Participants Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 n=3 Participants Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 n=4 Participants Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 n=6 Participants Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 n=3 Participants Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 MTD n=30 Participants Phase 2 MTD, oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Total n=52 Participants Total of all reporting groups
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	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=10 Participants	12 Participants n=115 Participants	22 Participants n=24 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=10 Participants	18 Participants n=115 Participants	30 Participants n=24 Participants
Age, Categorical <=18 years	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	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants	2 Participants n=10 Participants	19 Participants n=115 Participants	34 Participants n=24 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	11 Participants n=115 Participants	18 Participants n=24 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	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	1 Participants n=24 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	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	5 Participants n=115 Participants	7 Participants n=24 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	3 Participants n=10 Participants	17 Participants n=115 Participants	32 Participants n=24 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	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	7 Participants n=115 Participants	12 Participants n=24 Participants
Region of Enrollment United States	2 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	6 participants n=21 Participants	3 participants n=10 Participants	30 participants n=115 Participants	52 participants n=24 Participants
Immunoglobulin Isotype IgG Lambda	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	7 Participants n=115 Participants	12 Participants n=24 Participants
Immunoglobulin Isotype IgG Kappa	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=10 Participants	12 Participants n=115 Participants	16 Participants n=24 Participants
Immunoglobulin Isotype IgA Lambda	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	4 Participants n=115 Participants	5 Participants n=24 Participants
Immunoglobulin Isotype IgA Kappa	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants	3 Participants n=115 Participants	6 Participants n=24 Participants
Immunoglobulin Isotype IgD Kappa	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=24 Participants
Immunoglobulin Isotype Kappa Free light Chain	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=10 Participants	3 Participants n=115 Participants	10 Participants n=24 Participants
Immunoglobulin Isotype Lambda Free light Chain	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	2 Participants n=24 Participants

PRIMARY outcome

Timeframe: 12 months

Population: This outcome measure only assesses Phase 1 participants

The primary endpoint for the phase 1 portion of this study is to determine the maximum tolerated dose of lenalidomide that can be added to melphalan.

Outcome measures

Measure	All Phase 1 Participants n=21 Participants All participants who received lenalidomide at 25mg daily x 5 days 25mg twice daily x 5 days 25mg qAM, 50mq qPM x 5 days 50mg qAM, 75mg qPM x 5 days 75mg qAM, 100mg qPM x 5 days 100mg qAM, 150mg qPM x 5 days 150mg qAM, 200mg qPM x 5 days	Phase 1 Dose Level 2 Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 Expansion Early studies noted a dose response relationship and found myelosuppression to be the dose limiting toxicity. In this Phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT shown no DLT noted up to 350mg PO daily of LEN. In Phase 2, HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Maximum Tolerated Dose (MTD) of Lenalidomide That Can be Added to Melphalan	NA mg/day Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Until disease progression, death, or for a maximum of 3 years, whichever occurs first

Population: This outcome measure only assesses Phase 2 participants

The primary endpoint for the phase 2 portion of this study is to determine the duration of overall response (DoR). The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Outcome measures

Measure	All Phase 1 Participants n=28 Participants All participants who received lenalidomide at 25mg daily x 5 days 25mg twice daily x 5 days 25mg qAM, 50mq qPM x 5 days 50mg qAM, 75mg qPM x 5 days 75mg qAM, 100mg qPM x 5 days 100mg qAM, 150mg qPM x 5 days 150mg qAM, 200mg qPM x 5 days	Phase 1 Dose Level 2 Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 Expansion Early studies noted a dose response relationship and found myelosuppression to be the dose limiting toxicity. In this Phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT shown no DLT noted up to 350mg PO daily of LEN. In Phase 2, HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Duration of Overall Response (DoR) sCR	7 participants	—	—	—	—	—	—
Duration of Overall Response (DoR) CR	6 participants	—	—	—	—	—	—
Duration of Overall Response (DoR) VGPR	10 participants	—	—	—	—	—	—
Duration of Overall Response (DoR) PR	4 participants	—	—	—	—	—	—
Duration of Overall Response (DoR) SD	1 participants	—	—	—	—	—	—
Duration of Overall Response (DoR) PD	0 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Until disease progression or a maximum of 3 years, whichever occurs first

Overall response rate is the number of patients with complete response and partial response. Response is defined by the International Uniform Response Criteria for Multiple Myeloma (IURC)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Until death or date of last contact with the subject

Overall survival is defined as the interval between the day of transplantation (Day 0) and date of death. If the date of death is uncertain, the date of last contact with the subject will be used.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 6, day 1, at approximately 4.5 months

Population: Subjects from whom data were not collected were excluded from analysis.

quality of life will be evaluated and scored using the questionnaire from the bone marrow transplant subscale of the Functional Assessment of Cancer Therapy available from w ww.facit.org. The FACT-BMT is a 50 item questionnaire that measures five dimensions of quality of life in bone marrow transplant patients, including physical well-being, social and family well-being, emotional well-being, functional well-being, and additional concerns. It is scored on a 5 point Likert scale. Total scores range from 0 to 148, with a higher score indicating higher quality of life.

Outcome measures

Measure	All Phase 1 Participants n=1 Participants All participants who received lenalidomide at 25mg daily x 5 days 25mg twice daily x 5 days 25mg qAM, 50mq qPM x 5 days 50mg qAM, 75mg qPM x 5 days 75mg qAM, 100mg qPM x 5 days 100mg qAM, 150mg qPM x 5 days 150mg qAM, 200mg qPM x 5 days	Phase 1 Dose Level 2 n=3 Participants Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 n=2 Participants Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 n=3 Participants Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 n=6 Participants Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 n=3 Participants Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 Expansion n=21 Participants Early studies noted a dose response relationship and found myelosuppression to be the dose limiting toxicity. In this Phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT shown no DLT noted up to 350mg PO daily of LEN. In Phase 2, HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Mean Functional Assessment of of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Score	85.28 score on a scale Interval 0.0 to 148.0	69.3 score on a scale Interval 0.0 to 148.0	81.5 score on a scale Interval 0.0 to 148.0	70.13 score on a scale Interval 0.0 to 148.0	80.14 score on a scale Interval 0.0 to 148.0	79.33 score on a scale Interval 0.0 to 148.0	74.68 score on a scale Interval 0.0 to 148.0

Adverse Events

Phase 1 Dose Level 1

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Phase 1 Dose Level 2

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Phase 1 Dose Level 3

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Dose Level 4

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Dose Level 5

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase 1 Dose Level 6

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 2 MTD

Serious events: 8 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase 1 Dose Level 1 n=2 participants at risk Oral lenalidomide 25mg twice daily x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 2 n=4 participants at risk Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 n=3 participants at risk Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 n=4 participants at risk Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 n=6 participants at risk Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 n=3 participants at risk Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 MTD n=30 participants at risk Phase 2 MTD, oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Ataxia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Hepatobiliary disorders Cholecystitis	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Colitis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Dehydration	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Diarrhea	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
General disorders Fever	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Infections and infestations Infections and infestations - Other, specify	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Lung infection	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Myocardiac Infarction	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Investigations Platelet count decreased	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Presyncope	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Sepsis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Syncope	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Vascular disorders Thromboembolic event	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Urinary Incontinence	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Urinary Retention	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Ventricular Tachycardia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years

Other adverse events

Measure	Phase 1 Dose Level 1 n=2 participants at risk Oral lenalidomide 25mg twice daily x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 2 n=4 participants at risk Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 3 n=3 participants at risk Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 4 n=4 participants at risk Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 5 n=6 participants at risk Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 1 Dose Level 6 n=3 participants at risk Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1	Phase 2 MTD n=30 participants at risk Phase 2 MTD, oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1
Nervous system disorders Peripheral neuropathy	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	50.0% 3/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	43.3% 13/30 • Number of events 15 • Adverse events presented were collected for an average of 3 years
Infections and infestations Pharyngitis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Phlebitis infective	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Investigations Platelet count decreased	50.0% 1/2 • Number of events 2 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 8 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 6 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 15 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 9 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	96.7% 29/30 • Number of events 75 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Post nasal drip	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 5 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Rash	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	30.0% 9/30 • Number of events 13 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Rectal pain	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Rhinitis Infective	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 4 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Scalp pain	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Shingles	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Sinus bradycardia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Sinus disorder	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Sinus tachycardia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Sinusitis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Abdominal Distention	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Abdominal pain	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 5 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Investigations Activated PTT prolonged	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	36.7% 11/30 • Number of events 11 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Acute kidney Injury	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	50.0% 3/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Acute renal failure	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Investigations Alanine aminotransferase increased	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	66.7% 20/30 • Number of events 50 • Adverse events presented were collected for an average of 3 years
Investigations Alkaline phosphatase increased	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 13 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	53.3% 16/30 • Number of events 35 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Infections and infestations Acute otitis media	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Endocrine disorders Adrenal insufficiency	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Psychiatric disorders Agitation	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Amnesia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 4 • Adverse events presented were collected for an average of 3 years
Blood and lymphatic system disorders Anemia	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 8 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 4 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 8 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 6 • Adverse events presented were collected for an average of 3 years	93.3% 28/30 • Number of events 59 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Anorexia	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 5 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	63.3% 19/30 • Number of events 23 • Adverse events presented were collected for an average of 3 years
Psychiatric disorders Anxiety	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	20.0% 6/30 • Number of events 12 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 4 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	36.7% 11/30 • Number of events 13 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Investigations Aspartate aminotransferase increased	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	60.0% 18/30 • Number of events 46 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Atrial Fibrillation	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 13 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	46.7% 14/30 • Number of events 20 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Bloating	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 8 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	96.7% 29/30 • Number of events 96 • Adverse events presented were collected for an average of 3 years
Investigations Blood bilirubin increased	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 10/30 • Number of events 20 • Adverse events presented were collected for an average of 3 years
Eye disorders Blurred vision	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Bone pain	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
General disorders Chills	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Chronic kidney disease	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 7 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Colitis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Concentration impairement	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Psychiatric disorders Confusion	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Constipation	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 4 • Adverse events presented were collected for an average of 3 years	26.7% 8/30 • Number of events 16 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Cough	50.0% 1/2 • Number of events 2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	23.3% 7/30 • Number of events 8 • Adverse events presented were collected for an average of 3 years
Investigations CPK increase	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Investigations Creatinine increase	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	26.7% 8/30 • Number of events 13 • Adverse events presented were collected for an average of 3 years
Psychiatric disorders Depression	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Diarrhea	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 9 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 6 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 17 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 12 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 5 • Adverse events presented were collected for an average of 3 years	83.3% 25/30 • Number of events 53 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Dizziness	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 5 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Eye disorders Dry eyes	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Dry mouth	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 6 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 4 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Dysgeusia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	50.0% 3/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Dyspepsia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	20.0% 6/30 • Number of events 6 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Dysphagia	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	50.0% 3/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	23.3% 7/30 • Number of events 7 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Dysuria	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
General disorders Edema	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	26.7% 8/30 • Number of events 9 • Adverse events presented were collected for an average of 3 years
General disorders Edema limb	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 5 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Encephalopathy	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Enterocolitis	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Esophagitis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Eye disorders Eye disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Injury, poisoning and procedural complications Fall	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
General disorders Fatigue	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 7 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 14 • Adverse events presented were collected for an average of 3 years	83.3% 5/6 • Number of events 8 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 5 • Adverse events presented were collected for an average of 3 years	76.7% 23/30 • Number of events 38 • Adverse events presented were collected for an average of 3 years
Blood and lymphatic system disorders Febrile neutropenia	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	23.3% 7/30 • Number of events 7 • Adverse events presented were collected for an average of 3 years
General disorders Fever	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	23.3% 7/30 • Number of events 7 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Flatulence	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Eye disorders Floaters	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
General disorders Flu-like symptoms	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Vascular disorders Flushing	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Injury, poisoning and procedural complications Fracture	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
General disorders Gait alteration	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Gastroesophageal reflux	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Gastropharesis	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Generalized muscle weakness	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Gum infection	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Psychiatric disorders Hallucinations	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Headache	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 7 • Adverse events presented were collected for an average of 3 years
Ear and labyrinth disorders Hearing impaired	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Hematuria	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Herpes simplex reactivation	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Investigations Hypercalcemia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hyperglycemia	50.0% 1/2 • Number of events 2 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 8 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 5 • Adverse events presented were collected for an average of 3 years	83.3% 5/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 4 • Adverse events presented were collected for an average of 3 years	96.7% 29/30 • Number of events 68 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Hyperhidrosis	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 8 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	23.3% 7/30 • Number of events 9 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hyperlipidemia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 8 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypernatremia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 11 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Hyperpigmentation	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Hypertension	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	90.0% 27/30 • Number of events 50 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypocalcemia	50.0% 1/2 • Number of events 4 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 10 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 7 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 10 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 12 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	93.3% 28/30 • Number of events 84 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypoglycemia	50.0% 1/2 • Number of events 5 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 10 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 7 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 20 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	50.0% 15/30 • Number of events 24 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypokalemia	50.0% 1/2 • Number of events 5 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 6 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 7 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	83.3% 25/30 • Number of events 32 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hypomagnesemia	50.0% 1/2 • Number of events 6 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 5 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 6 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 18 • Adverse events presented were collected for an average of 3 years	83.3% 5/6 • Number of events 9 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 6 • Adverse events presented were collected for an average of 3 years	70.0% 21/30 • Number of events 62 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Hyponatremia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	43.3% 13/30 • Number of events 21 • Adverse events presented were collected for an average of 3 years
Vascular disorders Hypotension	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	16.7% 5/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Infections and infestations - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 8 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Injury, poisoning and procedural complications Infusion-Related Reaction	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Investigations INR increase	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	70.0% 21/30 • Number of events 28 • Adverse events presented were collected for an average of 3 years
Psychiatric disorders Insomnia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 10 • Adverse events presented were collected for an average of 3 years	50.0% 3/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	40.0% 12/30 • Number of events 24 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Intracranial Hemorrhage	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Lethargy	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Infections and infestations Lung infection	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Investigations Lymphocyte count decreased	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 18 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	96.7% 29/30 • Number of events 75 • Adverse events presented were collected for an average of 3 years
Investigations Lymphocyte count increase	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
General disorders Malaise	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 4 • Adverse events presented were collected for an average of 3 years
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Mucositis oral	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 3 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Muscle cramp	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Muscle weakness	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Myalgia	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Infections and infestations Nail infection	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 8 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Nausea	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 7 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	83.3% 5/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	70.0% 21/30 • Number of events 38 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Neuralgia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Investigations Neutrophil count decreased	50.0% 1/2 • Number of events 6 • Adverse events presented were collected for an average of 3 years	100.0% 4/4 • Number of events 15 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 10 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 18 • Adverse events presented were collected for an average of 3 years	100.0% 6/6 • Number of events 26 • Adverse events presented were collected for an average of 3 years	100.0% 3/3 • Number of events 9 • Adverse events presented were collected for an average of 3 years	96.7% 29/30 • Number of events 113 • Adverse events presented were collected for an average of 3 years
General disorders Non-cardiac Chest Pain	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
General disorders Pain	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 7 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	56.7% 17/30 • Number of events 42 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Paresthesia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 3 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 4 • Adverse events presented were collected for an average of 3 years
Surgical and medical procedures Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Syncope	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Cardiac disorders Tachycardia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Infections and infestations Thrush	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Ear and labyrinth disorders Tinnitus	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Tooth infection	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Toothache	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Tremor	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	10.0% 3/30 • Number of events 5 • Adverse events presented were collected for an average of 3 years
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	50.0% 1/2 • Number of events 1 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 7 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	50.0% 2/4 • Number of events 10 • Adverse events presented were collected for an average of 3 years	83.3% 5/6 • Number of events 9 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 3 • Adverse events presented were collected for an average of 3 years	63.3% 19/30 • Number of events 42 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Urinary frequency	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	13.3% 4/30 • Number of events 4 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Urinary incontinence	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Renal and urinary disorders Urinary retention	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	6.7% 2/30 • Number of events 2 • Adverse events presented were collected for an average of 3 years
Infections and infestations Urinary tract infection	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	50.0% 3/6 • Number of events 3 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Vascular disorders Vascular disorders - Other, specify	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Nervous system disorders Vasovagal reaction	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	3.3% 1/30 • Number of events 1 • Adverse events presented were collected for an average of 3 years
Ear and labyrinth disorders Vertigo	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Infections and infestations Viremia	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Gastrointestinal disorders Vomiting	50.0% 1/2 • Number of events 2 • Adverse events presented were collected for an average of 3 years	75.0% 3/4 • Number of events 4 • Adverse events presented were collected for an average of 3 years	66.7% 2/3 • Number of events 2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	66.7% 4/6 • Number of events 6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	26.7% 8/30 • Number of events 13 • Adverse events presented were collected for an average of 3 years
Eye disorders Watering eyes	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	16.7% 1/6 • Number of events 1 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/30 • Adverse events presented were collected for an average of 3 years
Musculoskeletal and connective tissue disorders Weakness	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 2 • Adverse events presented were collected for an average of 3 years	0.00% 0/6 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	23.3% 7/30 • Number of events 11 • Adverse events presented were collected for an average of 3 years
Investigations Weight loss	0.00% 0/2 • Adverse events presented were collected for an average of 3 years	25.0% 1/4 • Number of events 1 • Adverse events presented were collected for an average of 3 years	0.00% 0/3 • Adverse events presented were collected for an average of 3 years	0.00% 0/4 • Adverse events presented were collected for an average of 3 years	33.3% 2/6 • Number of events 2 • Adverse events presented were collected for an average of 3 years	33.3% 1/3 • Number of events 1 • Adverse events presented were collected for an average of 3 years	36.7% 11/30 • Number of events 11 • Adverse events presented were collected for an average of 3 years

Additional Information

Roger Pearse, M.D. PhD

Weill Cornell Medicine

Phone: 646-962-6500

Email: rnp2001@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place