Trial Outcomes & Findings for Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease (NCT NCT04514510)

NCT ID: NCT04514510

Last Updated: 2024-01-02

Results Overview

Mean change in plasma soluble P-selectin level comparing the baseline versus IQ or placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline and Day 28
• Results posted on: 2024-01-02

Participant Flow

Participant milestones

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Overall Study STARTED	23	23
Overall Study COMPLETED	22	22
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Overall Study Lost to Follow-up	0	1
Overall Study Randomized but did not receive Isoquercetin	1	0

Baseline Characteristics

Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease

Baseline characteristics by cohort

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=23 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=23 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.	Total n=46 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	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants	20 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	21 Participants n=5 Participants	22 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	23 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: One patient in the isoquercetin arm was randomized but withdrawn from the study before any treatment and did not provide baseline soluble P-selectin measurement nor contribute to this analysis. One patient in the placebo arm provided baseline soluble P-selectin and their change in P-selectin was obtained via a multiple imputation procedure. 45 participants (22 isoquercetin and 23 placebo) contributed to the analysis.

Mean change in plasma soluble P-selectin level comparing the baseline versus IQ or placebo.

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=23 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Mean Change in the Plasma Soluble P-selectin Level	0.74 ng/ml Standard Deviation 6.53	0.10 ng/ml Standard Deviation 4.54

SECONDARY outcome

Timeframe: Baseline and 28 days

Population: Analysis includes only participants that completed study

Mean Change in Plasma Protein Disulfide Isomerase Activity comparing baseline and end of study

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Mean Change in Plasma Protein Disulfide Isomerase Activity	-3.13 pMoles/min/µL Standard Deviation 10.91	1.95 pMoles/min/µL Standard Deviation 9.34

SECONDARY outcome

Timeframe: Baseline and Day 28

Population: Analysis includes only participants that completed study

Median change of Tissue Factor Vesicle Number comparing baseline and end of study

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Median Change of Tissue Factor Vesicle Number	39 microvesicles/mL Interval -115.0 to 1296.0	-382 microvesicles/mL Interval -1090.0 to 86.0

SECONDARY outcome

Timeframe: Baseline and Day 28

Population: Analysis includes only participants that completed study

Mean change in tissue factor vesicle procoagulant activity comparing baseline and end of study

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Mean Change in Tissue Factor Vesicle Procoagulant Activity	-427 Picomoles Standard Deviation 1868	-43 Picomoles Standard Deviation 1404

SECONDARY outcome

Timeframe: Baseline and Day 28

Population: Analysis includes only participants that completed study

Mean Change in D-Dimer comparing baseline and end of study

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Mean Change in D-Dimer	0.15 mcg/mL Standard Deviation 0.92	0.28 mcg/mL Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline and Day 28

Mean Change in Vascular Cell Adhesion Molecule (inflammation marker) comparing baseline to Day 28

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Mean Change in Vascular Cell Adhesion Molecule	-22.43 ng/mL Standard Deviation 291.42	-38.15 ng/mL Standard Deviation 180.24

SECONDARY outcome

Timeframe: Day 28

Population: Analysis includes those participants that completed the end of study Near-infrared spectroscopy (NIRS) procedure.

Median Relative Blood Flow Index (rBFI) determined by Near-infrared spectroscopy (NIRS).

Near-infrared spectroscopy (NIRS) is a noninvasive technology that measures blood flow by directing near-infrared light into tissue, collects scattered light due to red blood cell movements using photodiodes, and calculates the blood flow index (BFI) using the correlation diffusion equation (CDE). Briefly, participants were seated upright and NIRS probe and a blood pressure cuff was placed on the right arm and resting baseline data was collected for three minutes followed by occlusion of the blood flow for three minutes and reperfusion recorded for three minutes. The post-occlusion hyperemic reperfusion response represented as the relative Blood Flow Index (rBFI) is determined by normalizing the maximal change in light absorption following occlusion (dBFI) by the corresponding time interval (dt); (rBFI = dBFI/dt; unit (cm^2/s)/s)].

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=5 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=7 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Median Relative Blood Flow Index (rBFI) Determined by Near-infrared Spectroscopy (NIRS)	0.00000000082 (cm2/s)/s Interval 0.00000000046 to 0.0000000021	0.00000000037 (cm2/s)/s Interval 0.00000000021 to 0.0000000013

SECONDARY outcome

Timeframe: Baseline and Day 28

Population: Analysis includes only participants that completed study

Mean percent adherence to study drug. Adherence was defined as number of study drug pills participant took divided by number of study drug pills dispensed multiplied by 100.

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Mean Percent Adherence to Study Drug	96.2 percentage of adherence Standard Deviation 13.9	97.2 percentage of adherence Standard Deviation 4.7

SECONDARY outcome

Timeframe: Up to Day 56

Number of adverse events Grade 2 and above using Common Terminology Criteria for Adverse Events (CTCAE) 5.0

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=23 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=23 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Number of Adverse Events Grade 2 and Above Grade 2	8 Adverse Events	9 Adverse Events
Number of Adverse Events Grade 2 and Above Grade 3 and 4	1 Adverse Events	2 Adverse Events
Number of Adverse Events Grade 2 and Above Serious Adverse Events	8 Adverse Events	6 Adverse Events

SECONDARY outcome

Timeframe: Up to day 28

Population: Analysis includes only participants that completed study

Number of participants that tolerated study drug for full duration of study

Outcome measures

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=22 Participants Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=22 Participants Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Number of Participants That Tolerated Study Drug	22 Participants	22 Participants

Adverse Events

Participants With Sickle Cell Disease Receiving Isoquercetin

Serious events: 6 serious events

Other events: 9 other events

Deaths: 0 deaths

Participants With Sickle Cell Disease Receiving Placebo

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=23 participants at risk Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=23 participants at risk Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Congenital, familial and genetic disorders Sickle cell anemia with crisis	21.7% 5/23 • Number of events 5 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	17.4% 4/23 • Number of events 5 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Infections and infestations COVID-19	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Infections and infestations Lung infection	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Reproductive system and breast disorders Priapism	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Eye disorders Retinal detachment	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.

Other adverse events

Measure	Participants With Sickle Cell Disease Receiving Isoquercetin n=23 participants at risk Isoquercetin given 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.	Participants With Sickle Cell Disease Receiving Placebo n=23 participants at risk Placebo given once daily, by mouth for 28 days in participants with Sickle Cell Disease.
Gastrointestinal disorders Abdominal pain	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Gastrointestinal disorders Bloating	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Eye disorders Blurred vision	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Investigations Creatine phosphokinase increased	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Gastrointestinal disorders Colitis	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Congenital, familial and genetic disorders Chronic sickle cell pain	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Congenital, familial and genetic disorders Sickle cell anemia with crisis	8.7% 2/23 • Number of events 2 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	8.7% 2/23 • Number of events 2 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Gastrointestinal disorders Diarrhea	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Hepatobiliary disorders Gallbladder pain	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Infections and infestations COVID-19	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
General disorders Pain	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Skin and subcutaneous tissue disorders Rash acneiform	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Reproductive system and breast disorders Penile pain	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Eye disorders Retinopathy	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Vascular disorders Headache	0.00% 0/23 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.	4.3% 1/23 • Number of events 1 • Up to 56 days Investigators will assess the occurrence of adverse events (AEs) and serious adverse events (SAEs) at all patient evaluation time points during the study. Grade 2 and above plus clinically significant laboratory abnormalities whether volunteered by the patient, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.

Additional Information

Arun Shet, MD, PhD

National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Phone: 301.827.6808

Email: arun.shet@nih.gov

Results disclosure agreements

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