Trial Outcomes & Findings for Lisinopril or Coreg CR® in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab (NCT NCT01009918)

Last Updated: 2021-03-30

Results Overview

Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of Left Ventricular Ejection Fraction (LVEF). Number of Patients who experienced a cardiotoxicity.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

468 participants

Primary outcome timeframe

2 years

Results posted on

2021-03-30

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I Lisinopril Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo Patients receive oral placebo once daily. placebo: Given orally
Overall Study STARTED	158	156	154
Overall Study COMPLETED	134	132	124
Overall Study NOT COMPLETED	24	24	30

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Did not have information for 4 participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I Lisinopril n=158 Participants Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=156 Participants Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=154 Participants Patients receive oral placebo once daily. placebo: Given orally	Total n=468 Participants Total of all reporting groups
Age, Continuous	50.58 Years STANDARD_DEVIATION 10.91 • n=158 Participants	51.58 Years STANDARD_DEVIATION 10.93 • n=156 Participants	51.11 Years STANDARD_DEVIATION 10.32 • n=154 Participants	51.09 Years STANDARD_DEVIATION 10.71 • n=468 Participants
Sex: Female, Male Female	158 Participants n=158 Participants	156 Participants n=156 Participants	154 Participants n=154 Participants	468 Participants n=468 Participants
Sex: Female, Male Male	0 Participants n=158 Participants	0 Participants n=156 Participants	0 Participants n=154 Participants	0 Participants n=468 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=158 Participants	10 Participants n=156 Participants	16 Participants n=154 Participants	42 Participants n=468 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	141 Participants n=158 Participants	145 Participants n=156 Participants	137 Participants n=154 Participants	423 Participants n=468 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=158 Participants	1 Participants n=156 Participants	1 Participants n=154 Participants	3 Participants n=468 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=158 Participants	3 Participants n=156 Participants	0 Participants n=154 Participants	4 Participants n=468 Participants
Race (NIH/OMB) Asian	3 Participants n=158 Participants	6 Participants n=156 Participants	3 Participants n=154 Participants	12 Participants n=468 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=158 Participants	0 Participants n=156 Participants	1 Participants n=154 Participants	1 Participants n=468 Participants
Race (NIH/OMB) Black or African American	14 Participants n=158 Participants	5 Participants n=156 Participants	15 Participants n=154 Participants	34 Participants n=468 Participants
Race (NIH/OMB) White	137 Participants n=158 Participants	137 Participants n=156 Participants	130 Participants n=154 Participants	404 Participants n=468 Participants
Race (NIH/OMB) More than one race	1 Participants n=158 Participants	1 Participants n=156 Participants	1 Participants n=154 Participants	3 Participants n=468 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=158 Participants	4 Participants n=156 Participants	4 Participants n=154 Participants	10 Participants n=468 Participants
Body Mass Index (BMI)	28.01 kg/m^2 STANDARD_DEVIATION 6.86 • n=156 Participants • Did not have information for 4 participants	28.26 kg/m^2 STANDARD_DEVIATION 6.17 • n=156 Participants • Did not have information for 4 participants	29.03 kg/m^2 STANDARD_DEVIATION 5.92 • n=152 Participants • Did not have information for 4 participants	28.43 kg/m^2 STANDARD_DEVIATION 6.33 • n=464 Participants • Did not have information for 4 participants

PRIMARY outcome

Timeframe: 2 years

Population: Number of participants who experienced cardiotoxicity

Outcome measures

Outcome measures
Measure	Arm I Lisinopril n=152 Participants Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=147 Participants Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=144 Participants Patients receive oral placebo once daily. placebo: Given orally
Number of Participants With Trastuzumab-Induced Cardiotoxicity After 52 Weeks of Treatment	45 Participants	43 Participants	46 Participants

PRIMARY outcome

Timeframe: 2 years

Population: LVEF drop to \<50%

Number of Participants with Left Ventricular Ejection Fraction (LVEF) drop to \<50%

Outcome measures

Outcome measures
Measure	Arm I Lisinopril n=152 Participants Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=147 Participants Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=144 Participants Patients receive oral placebo once daily. placebo: Given orally
Number of Participants With LVEF Decrease to <50%	5 Participants	9 Participants	15 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Number of patients who had an interruption of trastuzumab for any reason

Measure indicates the number of patients who had an interruption of trastuzumab for any reason

Outcome measures

Outcome measures
Measure	Arm I Lisinopril n=152 Participants Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=147 Participants Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=144 Participants Patients receive oral placebo once daily. placebo: Given orally
Number of Patients With Trastuzumab Course Interruption	27 Participants	24 Participants	40 Participants

SECONDARY outcome

Timeframe: 52 weeks

Population: Mean change from baseline to 52-week endpoint

Quality-of-life changes as assessed by North European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), which measures the quality of life of cancer patients. Higher score indicates higher quality of life. Score range is 0-100. The questionnaire was administered at baseline and at 52 weeks.

Outcome measures

Outcome measures
Measure	Arm I Lisinopril n=128 Participants Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=129 Participants Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=111 Participants Patients receive oral placebo once daily. placebo: Given orally
Quality-of-life Changes Between Baseline and 52-weeks	1 Scores on a scale Standard Deviation 23	2 Scores on a scale Standard Deviation 17	5 Scores on a scale Standard Deviation 21

SECONDARY outcome

Timeframe: 2 years

Population: Number of Participants with cardiotoxicity-free survival at 750 days from baseline

Number of Participants with cardiotoxicity-free survival at 750 days from baseline

Outcome measures

Outcome measures
Measure	Arm I Lisinopril n=152 Participants Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=147 Participants Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=144 Participants Patients receive oral placebo once daily. placebo: Given orally
Number of Participants With Cardiotoxicity-free Survival at 750 Days From Baseline	15 Participants	24 Participants	17 Participants

Adverse Events

Arm I Lisinopril

Serious events: 5 serious events

Other events: 104 other events

Deaths: 1 deaths

Arm II Coreg CR®

Serious events: 4 serious events

Other events: 89 other events

Deaths: 2 deaths

Arm III Placebo

Serious events: 6 serious events

Other events: 82 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Maya Guglin, MD, PhD

University of South Florida

Phone: 813-259-0600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I Lisinopril n=158 participants at risk Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=156 participants at risk Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=154 participants at risk Patients receive oral placebo once daily. placebo: Given orally
Cardiac disorders Palpitations	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.65% 1/154 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Cardiac disorders Chest pain - cardiac	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.65% 1/154 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.65% 1/154 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Blood and lymphatic system disorders Anemia	0.63% 1/158 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Colitis	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.64% 1/156 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Metabolism and nutrition disorders Dehydration	1.3% 2/158 • Number of events 2 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Diarrhea	0.63% 1/158 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Nervous system disorders Dizziness	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.65% 1/154 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
General disorders Fatigue	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.64% 1/156 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.64% 1/156 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.64% 1/156 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Vascular disorders Hypotension	0.63% 1/158 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Nervous system disorders Nervous System Disorders - Other Specify	0.63% 1/158 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Investigations Neutrophil Count Decreased	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.64% 1/156 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	1.3% 2/154 • Number of events 3 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Cardiac disorders Pericardial Effusion	0.63% 1/158 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Infections and infestations Skin Infection	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.65% 1/154 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Blood and lymphatic system disorders Spleen Disorder	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.65% 1/154 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Nervous system disorders Syncope	0.63% 1/158 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/156 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Investigations White Blood Cell Count Decreased	0.00% 0/158 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.64% 1/156 • Number of events 1 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	0.00% 0/154 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.

Measure	Arm I Lisinopril n=158 participants at risk Patients receive oral lisinopril once daily. lisinopril: Given orally	Arm II Coreg CR® n=156 participants at risk Patients receive oral Coreg CR® once daily. Coreg CR®: Given orally	Arm III Placebo n=154 participants at risk Patients receive oral placebo once daily. placebo: Given orally
Blood and lymphatic system disorders Anemia	5.1% 8/158 • Number of events 21 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	7.1% 11/156 • Number of events 18 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	3.9% 6/154 • Number of events 8 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 9/158 • Number of events 10 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	5.1% 8/156 • Number of events 8 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	3.9% 6/154 • Number of events 7 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Constipation	6.3% 10/158 • Number of events 15 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	8.3% 13/156 • Number of events 14 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	3.2% 5/154 • Number of events 5 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 21/158 • Number of events 22 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	7.7% 12/156 • Number of events 17 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	4.5% 7/154 • Number of events 7 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Diarrhea	31.0% 49/158 • Number of events 134 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	32.1% 50/156 • Number of events 81 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	20.8% 32/154 • Number of events 68 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Nervous system disorders Dizziness	24.7% 39/158 • Number of events 60 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	19.2% 30/156 • Number of events 43 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	15.6% 24/154 • Number of events 53 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Dyspepsia	5.7% 9/158 • Number of events 9 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	5.8% 9/156 • Number of events 9 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	3.9% 6/154 • Number of events 8 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	19.6% 31/158 • Number of events 45 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	12.2% 19/156 • Number of events 28 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	13.6% 21/154 • Number of events 35 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
General disorders Edema Limbs	6.3% 10/158 • Number of events 10 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	10.3% 16/156 • Number of events 21 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	3.9% 6/154 • Number of events 6 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Fatigue	46.8% 74/158 • Number of events 130 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	40.4% 63/156 • Number of events 107 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	37.0% 57/154 • Number of events 126 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Nervous system disorders Headache	12.0% 19/158 • Number of events 27 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	8.3% 13/156 • Number of events 26 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	8.4% 13/154 • Number of events 23 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Vascular disorders Hot Flashes	3.8% 6/158 • Number of events 11 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	5.8% 9/156 • Number of events 10 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	4.5% 7/154 • Number of events 8 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Vascular disorders Hypotension	15.2% 24/158 • Number of events 39 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	4.5% 7/156 • Number of events 11 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	2.6% 4/154 • Number of events 5 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Musculoskeletal and connective tissue disorders Myalgia	7.6% 12/158 • Number of events 12 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	5.8% 9/156 • Number of events 9 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	3.2% 5/154 • Number of events 5 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Nausea	15.8% 25/158 • Number of events 36 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	14.1% 22/156 • Number of events 28 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	8.4% 13/154 • Number of events 16 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.
Gastrointestinal disorders Pain	5.1% 8/158 • Number of events 14 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	5.1% 8/156 • Number of events 10 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.	1.3% 2/154 • Number of events 2 • AEs were collected for the duration of the study and 12 month follow-up period. Adverse Events were collected from patient at each study visit.