Trial Outcomes & Findings for Idarubicin + Cytarabine and Lenalidomide in Patients With Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML) (NCT NCT00831766)

Last Updated: 2020-12-22

Results Overview

For the Phase I component, no formal statistical analysis was planned. The primary endpoint is to determine the maximum tolerated dose (MTD) and recommended Phase II dose of lenalidomide given in combination with standard idarubicin + cytarabine induction therapy.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

51 participants

Primary outcome timeframe

18 months

Results posted on

2020-12-22

Participant Flow

Participants were enrolled at Moffitt Cancer Center and Cleveland Clinic between June 2009 and March 2014.

Participant milestones

Participant milestones
Measure	Phase I: Dose Escalation Induction: A dose escalation plan for induction therapy using a standard 3x3 design with dose escalation of Lenalidomide only, to determine maximum tolerated dose (MTD). Idarubicin and cytarabine doses will be fixed. Idarubicin: 12 mg/m\^2. Cytarabine: 200 mg/m\^2. Lenalidomide: According to dose escalation levels. Level 1: 5 mg/d; Level 2: 10 mg/d; Level 3: 15 mg/d; Level 4: 20 mg/d; Level 5: 25 mg/d. Idarubicin: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Cytarabine: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Lenalidomide (Revlimid®): Lenalidomide as outlined in Phase I and Phase II Treatment Arms.	Phase II: Treatment at MTD Idarubicin: 12 mg/m\^2. Cytarabine: 200 mg/m\^2. Lenalidomide: Maximum Tolerated Dose (MTD). Idarubicin: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Cytarabine: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Lenalidomide (Revlimid®): Lenalidomide as outlined in Phase I and Phase II Treatment Arms.
Overall Study STARTED	23	28
Overall Study COMPLETED	23	28
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Idarubicin + Cytarabine and Lenalidomide in Patients With Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Dose Escalation n=23 Participants Induction: A dose escalation plan for induction therapy using a standard 3x3 design with dose escalation of Lenalidomide only, to determine maximum tolerated dose (MTD). Idarubicin and cytarabine doses will be fixed. Idarubicin: 12 mg/m\^2. Cytarabine: 200 mg/m\^2. Lenalidomide: According to dose escalation levels. Level 1: 5 mg/d; Level 2: 10 mg/d; Level 3: 15 mg/d; Level 4: 20 mg/d; Level 5: 25 mg/d. Idarubicin: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Cytarabine: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Lenalidomide (Revlimid®): Lenalidomide as outlined in Phase I and Phase II Treatment Arms.	Phase II: Treatment at MTD n=28 Participants Idarubicin: 12 mg/m\^2. Cytarabine: 200 mg/m\^2. Lenalidomide: Maximum Tolerated Dose (MTD). Idarubicin: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Cytarabine: Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms. Lenalidomide (Revlimid®): Lenalidomide as outlined in Phase I and Phase II Treatment Arms.	Total n=51 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	23 Participants n=7 Participants	38 Participants n=5 Participants
Age, Continuous	65 years n=5 Participants	70 years n=7 Participants	67.7 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	13 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	28 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: Phase I participants.

Outcome measures

Outcome measures
Measure	Phase I Participants n=23 Participants Dose escalation group.
Phase I: Recommended Phase II Dose	20 mg/day

PRIMARY outcome

Timeframe: 24 months

Population: All participants treated at MTD

Percentage of participants achieving CR/CRi. Complete Response (CR) plus Complete Response with Incomplete Count Recovery (CRi) rates. Response rates (CR + CRi) of lenalidomide following idarubicin and cytarabine induction therapy in older patients with previously untreated AML. A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of 100,000/μL. CRi: After chemotherapy, patients fulfill all of the criteria for CR except for residual neutropenia (1,000/μL) or thrombocytopenia (100,000/μL).

Outcome measures

Outcome measures
Measure	Phase I Participants n=39 Participants Dose escalation group.
Phase II: Complete Response Rate of Participants Treated at Maximum Tolerated Dose (MTD)	54 percentage of participants

SECONDARY outcome

Timeframe: 24 months

Population: All Maintenance Phase participants.

Rate of toxicities of lenalidomide as maintenance therapy according to the National Cancer Institute Common Toxicity Criteria (CTC) V3. Adverse Events: Possibly Related; Probably Related, or Definitely Related to study treatment. Events are categorized as Grade 1 or 2, or as Grade 3 or 4.

Outcome measures

Outcome measures
Measure	Phase I Participants n=6 Participants Dose escalation group.
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Leukocytes (total WBC) - low - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Leukocytes (total WBC) - low - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy ANC/AGC - Grade 3 or 4	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Dry skin - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Constipation - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Diarrhea - Grade 1 or 2	2 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Diarrhea - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Ulcer, GI - Anus - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy AST, SGOT - Grade 1 of 2	2 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy AST, SGOT - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Pain - Head/headache - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy ANC/AGC - Grade 1 or 2	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Platelets - low - Grade 1 or 2	3 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Platelets - low - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Fatigue - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Fatigue - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Dry skin - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Pruritus/itching - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Pruritus/itching - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Rash/desquamation - Grade 1 or 2	2 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Rash/desquamation - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Constipation - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Nausea - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Nausea - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Ulcer, GI - Anus - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Hemorrhage, GI - Rectum - Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Hemorrhage, GI - Rectum - Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Infection - Skin (cellulitis) Grade 1 or 2	1 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Infection - Skin (cellulitis) Grade 3 or 4	0 Participants
Rate of Lenalidomide Related Toxicity During Maintenance Therapy Pain - Head/headache - Grade 3 or 4	0 Participants

SECONDARY outcome

Timeframe: 24 months

Population: All participants treated at MTD.

Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse, or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Phase I Participants n=39 Participants Dose escalation group.
Median Progression-Free Survival (PFS)	7.55 months Interval 5.53 to 10.53

SECONDARY outcome

Timeframe: Up to 24 Months

Population: All participants treated at MTD

Overall Survival (OS), defined for those patients who have achieved CR or CRi as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, to be analyzed similarly. Descriptive analysis was planned for this measure.

Outcome measures

Outcome measures
Measure	Phase I Participants n=39 Participants Dose escalation group.
Median Overall Survival (OS)	11.22 months Interval 7.61 to 13.74

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 Months

Rate of cytogenetic remission following induction therapy. Descriptive analysis was planned for this measure.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 Months

Relapse-Free Survival (RFS), defined for those patients who have achieved CR or CRi as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be analyzed similarly. Descriptive analysis was planned for this measure.

Outcome measures

Outcome data not reported

Adverse Events

Phase I: Dose Escalation

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Phase II: Treatment at MTD

Serious events: 13 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Jeffrey Lancet

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-1387

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I: Dose Escalation n=23 participants at risk Participants enrolled during Phase I.	Phase II: Treatment at MTD n=28 participants at risk Participants enrolled during Phase II.
Cardiac disorders Cardiac ischemia/infarction	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Cardiac disorders Left ventricular systolic dysfunction	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
General disorders Fever (in the absence of neutropenia)	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
General disorders Death - Disease progression NOS	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
General disorders Death - Multi-organ failure	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Gastrointestinal disorders Anorexia	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Gastrointestinal disorders Dehydration	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Gastrointestinal disorders Diarrhea	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	7.1% 2/28 • Number of events 3 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Gastrointestinal disorders Mucositis/stomatitis - Oral cavity	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Infections and infestations Febrile neutropenia	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	32.1% 9/28 • Number of events 9 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Infections and infestations Infection with Grade 3 or 4 neutrophils - abdomen, NOS	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Infections and infestations Infection with Grade 3 or 4 neutrophils - Blood	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	17.9% 5/28 • Number of events 5 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Infections and infestations Infection with Grade 3 or 4 neutrophils - Lung (pneumonia)	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophnils - Gallbladder (cholecystitis)	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Metabolism and nutrition disorders AST, SGOT - high	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Nervous system disorders Confusion	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
General disorders Pain - Extremity, limb	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.3% 1/23 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	0.00% 0/28 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Renal and urinary disorders Renal/Genitourinary - Other, acute kidney injury	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Vascular disorders Thrombosis/embolism (vascular access-related)	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Infections and infestations Infection with Grade 3 or 4 Neutrophils - Urinary Tract	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Blood and lymphatic system disorders Neutrophils/granulocytes - low	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Blood and lymphatic system disorders Platelets - low	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	7.1% 2/28 • Number of events 2 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Cardiac disorders Cardiac Arrhythmia - Other, atrial fibrilation with rapid ventricular response	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.
Cardiac disorders Supraventricular and nodal arrhythmai - atrial fibirillation	0.00% 0/23 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.	3.6% 1/28 • Number of events 1 • 4 years, 8 months All Serious Adverse Events (SAEs) are reported, regardless of causality. All Other (not including Serious) Adverse Events (AEs) meeting 5% frequency threshold are reported, regardless of causality.