Trial Outcomes & Findings for Study With Oral Ferric Maltol for the Treatment of Iron Deficiency Anemia in Subjects With Chronic Kidney Disease (NCT NCT02968368)

NCT ID: NCT02968368

Last Updated: 2020-11-02

Results Overview

Change in hemoglobin concentration from baseline to Week 16.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

167 participants

Primary outcome timeframe

16 weeks

Results posted on

2020-11-02

Participant Flow

Participant milestones

Participant milestones
Measure	Oral Ferric Maltol 30mg capsules BID Ferric maltol	Oral Placebo Matching placebo capsules BID Placebo
Double Blind Phase STARTED	111	56
Double Blind Phase COMPLETED	90	39
Double Blind Phase NOT COMPLETED	21	17
Open Label Phase STARTED	86	39
Open Label Phase COMPLETED	67	25
Open Label Phase NOT COMPLETED	19	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study With Oral Ferric Maltol for the Treatment of Iron Deficiency Anemia in Subjects With Chronic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo	Total n=167 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	34 Participants n=5 Participants	19 Participants n=7 Participants	53 Participants n=5 Participants
Age, Categorical >=65 years	77 Participants n=5 Participants	37 Participants n=7 Participants	114 Participants n=5 Participants
Age, Continuous	68.5 years STANDARD_DEVIATION 12.43 • n=5 Participants	65.2 years STANDARD_DEVIATION 12.79 • n=7 Participants	67.4 years STANDARD_DEVIATION 12.61 • n=5 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	39 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	17 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants	14 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants n=5 Participants	42 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 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
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	12 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) White	81 Participants n=5 Participants	42 Participants n=7 Participants	123 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	111 participants n=5 Participants	56 participants n=7 Participants	167 participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: ITT

Change in hemoglobin concentration from baseline to Week 16.

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=88 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=40 Participants Matching placebo capsules BID Placebo
Change in Hb Concentration From Baseline to Week 16	0.50 g/dl Standard Deviation 0.122	-0.02 g/dl Standard Deviation 0.165

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT

Number of subjects that achieve an increase in Hemoglobin concentration of ≥1 g/dL at Week 16

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Number of Subjects That Achieve an Increase in Hb Concentration of ≥1 g/dL at Week 16	22 Participants	5 Participants

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT

Number of subjects that achieve a Hemoglobin concentration of ≥11 g/dL at week 16

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Number of Subjects That Achieve a Hb Concentration of ≥11 g/dL at Week 16	30 Participants	7 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Where a subject had dropped from the study, we used a LOCF by MI methodology to impute values. Therefore the number of subjects and observations at a given time-point may differ.

Change in Hemoglobin concentration from baseline to Week 8

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=98 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=47 Participants Matching placebo capsules BID Placebo
Change in Hb Concentration From Baseline to Week 8	0.53 g/dl Standard Deviation 0.901	0.00 g/dl Standard Deviation 0.909

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT

Number of subjects that achieve an increase in Hemoglobin concentration of ≥2 g/dL at Week 16

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Number of Subjects That Achieve an Increase in Hb Concentration of ≥2 g/dL at Week 16	7 Participants	0 Participants

SECONDARY outcome

Timeframe: baseline to week 16

Population: ITT OC

Changes in iron parameter - ferritin - from baseline to week 16

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Changes in Ferritin From Baseline to Week 16	33.13 ug/l Standard Deviation 6.166	-5.90 ug/l Standard Deviation 9.137

SECONDARY outcome

Timeframe: Week 16

Population: safety population

Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Number of Participants With (TEAEs)	75 Participants	42 Participants

SECONDARY outcome

Timeframe: Week 16

Population: safety population

Number of Participants with Treatment-Emergent Serious Adverse Events (TESAEs) during the double blind phase

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)	23 Participants	12 Participants

SECONDARY outcome

Timeframe: baseline to week 16

Population: ITT OC

Changes in iron parameters - TSAT - from baseline to week 16

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Changes in TSAT From Baseline to Week 16	4.32 TSAT (%) Standard Deviation 0.719	-0.15 TSAT (%) Standard Deviation 1.060

SECONDARY outcome

Timeframe: from baseline to week 16

Population: ITT OC

Changes in iron parameters - serum iron - from baseline to week 16

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=111 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=56 Participants Matching placebo capsules BID Placebo
Changes in Iron Parameter From Baseline to Week 16	1.87 umol/l Standard Deviation 0.397	0.01 umol/l Standard Deviation 0.586

SECONDARY outcome

Timeframe: Week 52

Population: safety population

Number of Participants with Treatment-Emergent Adverse Events (TEAEs) during the open label phase

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=86 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=39 Participants Matching placebo capsules BID Placebo
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	76 Participants	35 Participants

SECONDARY outcome

Timeframe: Week 52

Population: safety population

Number of Participants with Treatment-Emergent Serious Adverse Events (TESAEs) during the open label phase

Outcome measures

Outcome measures
Measure	Oral Ferric Maltol n=86 Participants 30mg capsules BID Ferric maltol	Oral Placebo n=39 Participants Matching placebo capsules BID Placebo
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)	27 Participants	9 Participants

Adverse Events

Oral Ferric Maltol DB

Serious events: 23 serious events

Other events: 75 other events

Deaths: 75 deaths

Oral Placebo DB

Serious events: 12 serious events

Other events: 42 other events

Deaths: 42 deaths

Oral Ferric Maltol OL

Serious events: 27 serious events

Other events: 76 other events

Deaths: 76 deaths

Oral Placebo OL

Serious events: 9 serious events

Other events: 35 other events

Deaths: 35 deaths

Serious adverse events

Other adverse events

Additional Information

Jackie Mitchell MA DPhil

Shield Therapeutics

Phone: +44 (0) 191 511 8515

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Oral Ferric Maltol DB n=111 participants at risk 30mg capsules BID Ferric maltol double blind phase	Oral Placebo DB n=56 participants at risk Matching placebo capsules BID Placebo double blind phase	Oral Ferric Maltol OL n=86 participants at risk 30mg capsules BID Ferric maltol open label phase	Oral Placebo OL n=39 participants at risk Matching placebo capsules BID Placebo open label phase
Gastrointestinal disorders Diarrhea	9.0% 10/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.9% 5/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	12.8% 5/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Gastrointestinal disorders Nausea	8.1% 9/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.9% 5/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	11.6% 10/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	12.8% 5/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Gastrointestinal disorders Constipation	8.1% 9/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	3.6% 2/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	16.3% 14/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	12.8% 5/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Gastrointestinal disorders Feces discolored	7.2% 8/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	1.8% 1/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	2.6% 1/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Metabolism and nutrition disorders Metabolism and nutrition disorders	18.9% 21/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	23.2% 13/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	29.1% 25/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	33.3% 13/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Metabolism and nutrition disorders Hyperkalemia	3.6% 4/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	12.5% 7/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.8% 5/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	15.4% 6/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Infections and infestations Infections and infestations	15.3% 17/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	23.2% 13/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	45.3% 39/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	48.7% 19/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Infections and infestations Urinary tract infection	6.3% 7/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.9% 5/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.3% 4/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Renal and urinary disorders Renal and urinary disorders	9.0% 10/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.7% 6/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Renal and urinary disorders Acute kidney injury	4.5% 5/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	7.1% 4/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Blood and lymphatic system disorders Blood and lymphatic system disorders	4.5% 5/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	16.1% 9/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Blood and lymphatic system disorders Anemia	3.6% 4/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.7% 6/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Gastrointestinal disorders Gastrointestinal disorders	40.5% 45/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	30.4% 17/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	55.8% 48/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	46.2% 18/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Gastrointestinal disorders Vomiting	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
General disorders General disorders and administration site conditions	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	18.6% 16/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	12.8% 5/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
General disorders Fatigue	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	7.0% 6/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	2.6% 1/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
General disorders Edema peripheral	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.1% 2/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Infections and infestations Bronchitis	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.8% 5/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.3% 4/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Infections and infestations Nasopharyngitis	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.5% 9/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	7.7% 3/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Infections and infestations Pneumonia	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.1% 2/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Infections and infestations Upper respiratory tract infection	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	9.3% 8/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.3% 4/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Injury, poisoning and procedural complications Injury, poisoning, and procedural complications	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	19.8% 17/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	10.3% 4/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Injury, poisoning and procedural complications Fall	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	8.1% 7/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	2.6% 1/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic, and mediastinal disorders	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	22.1% 19/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	17.9% 7/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.8% 5/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.1% 2/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Vascular disorders Vascular disorders	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	18.6% 16/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	12.8% 5/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions
Vascular disorders Hypertension	0.00% 0/111 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	0.00% 0/56 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	5.8% 5/86 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions	7.7% 3/39 • 16 week double blind phase 167 subjects. Definitions of AEs and SAEs in line with clintrials.gov definitions