Trial Outcomes & Findings for Perindopril Amlodipine for the Treatment of Hypertension (NCT NCT01556997)

NCT ID: NCT01556997

Last Updated: 2015-09-28

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 837 participants
• Primary outcome timeframe: Day 0 to Day 42
• Results posted on: 2015-09-28

Participant Flow

Participant milestones

Measure	XOMA 985 fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Overall Study STARTED	279	280	278
Overall Study COMPLETED	253	252	246
Overall Study NOT COMPLETED	26	28	32

Reasons for withdrawal

Measure	XOMA 985 fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Overall Study Adverse Event	10	12	12
Overall Study Lost to Follow-up	6	6	4
Overall Study Physician Decision	1	1	1
Overall Study Withdrawal by Subject	7	6	8
Overall Study Other	2	3	7

Baseline Characteristics

Perindopril Amlodipine for the Treatment of Hypertension

Baseline characteristics by cohort

Measure	XOMA 985 n=279 Participants fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) n=280 Participants Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) n=278 Participants Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks	Total n=837 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	261 Participants n=5 Participants	262 Participants n=7 Participants	254 Participants n=5 Participants	777 Participants n=4 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants	60 Participants n=4 Participants
Sex: Female, Male Female	134 Participants n=5 Participants	130 Participants n=7 Participants	143 Participants n=5 Participants	407 Participants n=4 Participants
Sex: Female, Male Male	145 Participants n=5 Participants	150 Participants n=7 Participants	135 Participants n=5 Participants	430 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	47 Participants n=5 Participants	43 Participants n=7 Participants	52 Participants n=5 Participants	142 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	232 Participants n=5 Participants	237 Participants n=7 Participants	226 Participants n=5 Participants	695 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	95 Participants n=5 Participants	96 Participants n=7 Participants	96 Participants n=5 Participants	287 Participants n=4 Participants
Race (NIH/OMB) White	179 Participants n=5 Participants	181 Participants n=7 Participants	180 Participants n=5 Participants	540 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Black	95 participants n=5 Participants	96 participants n=7 Participants	96 participants n=5 Participants	287 participants n=4 Participants
Race/Ethnicity, Customized Non-black	184 participants n=5 Participants	184 participants n=7 Participants	182 participants n=5 Participants	550 participants n=4 Participants
Region of Enrollment United States	279 participants n=5 Participants	280 participants n=7 Participants	278 participants n=5 Participants	837 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 42

Population: The Analysis Population for the Primary Outcome (Change from baseline to end of treatment in the mean seated trough cuff diastolic blood pressure (DBP)) consists of the Intent-to-treat population for the study

Outcome measures

Measure	XOMA 985 n=271 Participants fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) n=275 Participants Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) n=274 Participants Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Change From Baseline to End of Treatment in the Mean Seated Trough Cuff Diastolic Blood Pressure (DBP).	-15.7 mmHg Standard Deviation 8.38	-13.2 mmHg Standard Deviation 8.33	-9.5 mmHg Standard Deviation 8.77

SECONDARY outcome

Timeframe: Day 0 to Day 42

Population: The Analysis Population for the Secondary Outcome (Change from baseline to end of treatment in the mean seated trough cuff systolic blood pressure (SBP)) consists of the Intent-to-treat population for the study

Outcome measures

Measure	XOMA 985 n=271 Participants fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) n=275 Participants Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) n=274 Participants Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Change From Baseline to End of Treatment in the Mean Seated Trough Cuff Systolic Blood Pressure (SBP).	-23.4 mmHg Standard Deviation 13.86	-19.6 mmHg Standard Deviation 15.62	-13.4 mmHg Standard Deviation 14.66

Adverse Events

XOMA 985

Serious events: 1 serious events

Other events: 75 other events

Deaths: 0 deaths

Amlodipine Besylate (AMLb)

Serious events: 3 serious events

Other events: 68 other events

Deaths: 0 deaths

Perindopril Erbumine (PERe)

Serious events: 2 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Measure	XOMA 985 n=279 participants at risk fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) n=280 participants at risk Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) n=278 participants at risk Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
Gastrointestinal disorders Lip Swelling	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Renal and urinary disorders Renal Failure Acute	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Vascular disorders Hypotension	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/280 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Gastrointestinal disorders Gastrointestinal Hemorrhage	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/280 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/280 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.36% 1/279 • Number of events 1 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.

Other adverse events

Measure	XOMA 985 n=279 participants at risk fixed-dose combination of perindopril arginine/amlodipine besylate(PERa/AMLb) XOMA 985: PERa/AMLb capsule taken once daily by mouth for six weeks	Amlodipine Besylate (AMLb) n=280 participants at risk Amlodipine Besylate: AMLb capsule taken once daily by mouth for six weeks	Perindopril Erbumine (PERe) n=278 participants at risk Perindopril Erbumine: PERe capsule taken once daily by mouth for six weeks
General disorders Edema peripheral	7.2% 20/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	12.5% 35/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
General disorders Fatigue	1.8% 5/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.71% 2/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.4% 4/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Nervous system disorders Headache	2.5% 7/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	2.9% 8/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	2.9% 8/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Nervous system disorders Dizziness	2.5% 7/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.4% 4/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Gastrointestinal disorders Diarrhea	1.1% 3/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.8% 5/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Gastrointestinal disorders Nausea	0.72% 2/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.71% 2/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.4% 4/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Infections and infestations Nasopharyngitis	1.1% 3/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Infections and infestations Urinary tract infection	1.4% 4/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Musculoskeletal and connective tissue disorders Arthralgia	0.72% 2/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.71% 2/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Musculoskeletal and connective tissue disorders Back pain	1.1% 3/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.71% 2/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.72% 2/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Respiratory, thoracic and mediastinal disorders Cough	3.2% 9/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.71% 2/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	2.9% 8/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Investigations Alanine amniotransferase increased	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.4% 4/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Investigations Aspartate amniotransferase increased	0.36% 1/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Investigations Blood potassium increased	0.00% 0/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Skin and subcutaneous tissue disorders Erythema	1.1% 3/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Skin and subcutaneous tissue disorders Rash	0.36% 1/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Renal and urinary disorders Hematuria	0.72% 2/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.1% 3/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.36% 1/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.
Renal and urinary disorders Pollakiuria	0.36% 1/279 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	1.4% 4/280 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.	0.00% 0/278 AE reporting began with Visit 1 and continued through 14 days after last dose, unless an unresolved AE was still being followed. At each evaluation, the Investigator determined whether any AEs occurred based on the criteria and definition of an AE or SAE. AEs may have been directly observed, elicited by Investigator, or volunteered by subjects.

Additional Information

Jeff Feldstein, Sr. Vice President and CMO

Symplmed Pharmaceuticals LLC

Phone: 888-552-9769

Email: feldstein@symplmed.com

Results disclosure agreements

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