Trial Outcomes & Findings for Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis? (NCT NCT02908490)

NCT ID: NCT02908490

Last Updated: 2021-08-13

Results Overview

The methods of assessment of endothelial function via FMD will be performed following guidelines. Using Duplex ultrasound with a high-resolution linear array transducer, the difference between the maximum brachial artery diameter (BAD) postocclusion and the baseline diameter will be calculated, expressed as a percentage (%BAD). Generally, %BAD values below 5-7% represent endothelial dysfunction, which is associated with CV risk factors, future CVD and mortality.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)
• Results posted on: 2021-08-13

Participant Flow

Participant milestones

Measure	Initial Sildenafil Sildenafil 50 mg orally once daily for first 3 months, then after 2-week washout, Placebo orally once daily for 3 months Sildenafil: Sildenafil 50 mg once daily Placebo: Placebo once daily with same size, shape, color, and texture as Sildenafil 50 mg pill	Initial Placebo Placebo orally once daily for first 3 months, then after 2-week washout, Sildenafil 50 mg orally once daily for 3 months Sildenafil: Sildenafil 50 mg once daily Placebo: Placebo once daily with same size, shape, color, and texture as Sildenafil 50 mg pill
Overall Study STARTED	12	13
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Does Sildenafil Improve Endothelial Dysfunction in Rheumatoid Arthritis?

Baseline characteristics by cohort

Measure	Initial Sildenafil n=12 Participants Sildenafil 50 mg orally once daily for first 3 months, then after 2-week washout, Placebo orally once daily for 3 months Sildenafil: Sildenafil 50 mg once daily Placebo: Placebo once daily with same size, shape, color, and texture as Sildenafil 50 mg pill	Initial Placebo n=13 Participants Placebo orally once daily for first 3 months, then after 2-week washout, Sildenafil 50 mg orally once daily for 3 months Sildenafil: Sildenafil 50 mg once daily Placebo: Placebo once daily with same size, shape, color, and texture as Sildenafil 50 mg pill	Total n=25 Participants Total of all reporting groups
Age, Continuous	61.1 years STANDARD_DEVIATION 11.2 • n=5 Participants	62.9 years STANDARD_DEVIATION 11.1 • n=7 Participants	62.0 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	13 Participants n=7 Participants	23 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	13 participants n=7 Participants	25 participants n=5 Participants
Cardiovascular Risk Factors Older age	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Cardiovascular Risk Factors Obesity	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Cardiovascular Risk Factors Smoking (ever or current)	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Cardiovascular Risk Factors Hypertension	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Cardiovascular Risk Factors Hyperlipidemia	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Cardiovascular Risk Factors Diabetes mellitus	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Cardiovascular Risk Factors Family history of CVD	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Cardiovascular Risk Factors Postmenopausal	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Cardiovascular Risk Factors Estrogen replacement use	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

The methods of assessment of endothelial function via FMD will be performed following guidelines. Using Duplex ultrasound with a high-resolution linear array transducer, the difference between the maximum brachial artery diameter (BAD) postocclusion and the baseline diameter will be calculated, expressed as a percentage (%BAD). Generally, %BAD values below 5-7% represent endothelial dysfunction, which is associated with CV risk factors, future CVD and mortality.

Outcome measures

Measure	Sildenafil Period n=20 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in Brachial Artery Flow Mediated Dilation (FMD) Without Nitroglycerin at 3 Months FMD at Baseline	7.06 percent of BAD Standard Deviation 4.05	6.48 percent of BAD Standard Deviation 3.23
Change From Baseline in Brachial Artery Flow Mediated Dilation (FMD) Without Nitroglycerin at 3 Months Change in FMD from Baseline at 3 Months	-1.14 percent of BAD Standard Deviation 4.72	0.814 percent of BAD Standard Deviation 2.98

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

PAT measured by the EndoPAT 2000 device is a non-invasive method to assess endothelial function. It is a standardized, rapid, and easy to apply method, and has been found to correlate with multiple traditional CV risk factors and to be responsive to interventions. PAT is a validated alternative measure to brachial arterial FMD in assessing endothelial function, and is less operator-dependent than FMD. FMD directly measures the dilation capability of the large-conduit artery, whereas PAT measures flow response hyperemia, which is related to endothelial function of small arteries of microcirculation. PAT measures endothelium-mediated changes in vascular tone using bio-sensors placed on fingertips. The semi-automatically calculated result (Reactive Hyperemia Index) is an index of endothelial function. LnRHI is a Reactive Hyperemia Index after natural log transformation with a matched cutoff: Normal: LnRHI > 0.51 and Abnormal: LnRHI <= 0.51 cut-off.

Outcome measures

Measure	Sildenafil Period n=19 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=20 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in Peripheral Arterial Tone (PAT) LnRHI at 3 Months LnRHI at Baseline	0.77 LnRHI Standard Deviation 0.29	0.78 LnRHI Standard Deviation 0.32
Change From Baseline in Peripheral Arterial Tone (PAT) LnRHI at 3 Months Change in LnRHI from Baseline at 3 Months	0.21 LnRHI Standard Deviation 0.54	-0.01 LnRHI Standard Deviation 0.35

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

High-sensitivity CRP (hsCRP) measured using standard clinical laboratory protocols

Outcome measures

Measure	Sildenafil Period n=20 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=20 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in hsCRP at 3 Months hsCRP at Baseline	0.43 mg/dL Standard Deviation 0.43	0.58 mg/dL Standard Deviation 0.63
Change From Baseline in hsCRP at 3 Months Change in hsCRP from Baseline at 3 Months	0.08 mg/dL Standard Deviation 0.42	0.43 mg/dL Standard Deviation 2.55

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Erythrocyte sedimentation rate (ESR) measured using standard clinical laboratory protocols

Outcome measures

Measure	Sildenafil Period n=20 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=20 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in ESR at 3 Months ESR at Baseline	19.22 mm/hr Standard Deviation 15.64	17.35 mm/hr Standard Deviation 10.25
Change From Baseline in ESR at 3 Months Change in ESR from Baseline at 3 Months	3.30 mm/hr Standard Deviation 5.73	3.95 mm/hr Standard Deviation 10.83

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Interleukin (IL)-6 measured using enzyme linked immunosorbent assay (ELISA) (pg/mL). Since very few subjects had detectable IL-6 levels, the outcome measure reports the number of participants with detectable IL-6 rather than mean levels.

Outcome measures

Measure	Sildenafil Period n=16 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in Number of Participants With Detectable IL-6 at 3 Months Number (%) of Participants with Detectable IL-6 at Baseline	3 Participants	8 Participants
Change From Baseline in Number of Participants With Detectable IL-6 at 3 Months Change (decrease) in Number (%) of Participants with Detectable IL-6 from Baseline at 3 Months	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Rheumatoid factor (RF) measured using standard clinical laboratory protocols

Outcome measures

Measure	Sildenafil Period n=20 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=20 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in RF at 3 Months RF at Baseline	128.17 IU/ml Standard Deviation 337.02	138.96 IU/ml Standard Deviation 296.77
Change From Baseline in RF at 3 Months Change in RF from Baseline at 3 Months	20.00 IU/ml Standard Deviation 81.29	-16.20 IU/ml Standard Deviation 59.47

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Anti-cyclic citrullinated peptide antibody (CCP) measured using standard clinical laboratory protocols. Note, the universal unit of measure for CCP is "Units."

Outcome measures

Measure	Sildenafil Period n=20 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=20 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in CCP at 3 Months CCP at Baseline	60.00 Units Standard Deviation 107.17	62.80 Units Standard Deviation 105.11
Change From Baseline in CCP at 3 Months Change in CCP from Baseline at 3 Months	-10.70 Units Standard Deviation 38.93	-10.70 Units Standard Deviation 32.17

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Leukocyte adhesion molecule E-selectin measured using enzyme linked immunosorbent assay (ELISA)

Outcome measures

Measure	Sildenafil Period n=16 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in E-selectin at 3 Months E-Selectin at Baseline	37.10 ng/mL Standard Deviation 14.68	42.56 ng/mL Standard Deviation 14.63
Change From Baseline in E-selectin at 3 Months Change in E-Selectin from Baseline at 3 Months	4.91 ng/mL Standard Deviation 13.37	-2.56 ng/mL Standard Deviation 11.42

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Intercellular adhesion molecule (ICAM)-1 measured using enzyme linked immunosorbent assay (ELISA)

Outcome measures

Measure	Sildenafil Period n=16 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in ICAM-1 at 3 Months ICAM-1 at Baseline	256.23 ng/mL Standard Deviation 65.96	299.59 ng/mL Standard Deviation 81.80
Change From Baseline in ICAM-1 at 3 Months Change in ICAM-1 from Baseline at 3 Months	26.31 ng/mL Standard Deviation 77.03	-44.33 ng/mL Standard Deviation 67.97

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Vascular cell adhesion molecule (VCAM)-1 measured using enzyme linked immunosorbent assay (ELISA)

Outcome measures

Measure	Sildenafil Period n=16 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in VCAM-1 at 3 Months VCAM-1 at Baseline	751.30 ng/mL Standard Deviation 294.35	771.86 ng/mL Standard Deviation 231.11
Change From Baseline in VCAM-1 at 3 Months Change in VCAM-1 from Baseline at 3 Months	46.12 ng/mL Standard Deviation 117.2	-33.23 ng/mL Standard Deviation 123.4

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

CD40 ligand (CD40L) measured using enzyme linked immunosorbent assay (ELISA)

Outcome measures

Measure	Sildenafil Period n=15 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in CD40L at 3 Months CD40L at Baseline	7650.22 pg/mL Standard Deviation 6994.27	10316.24 pg/mL Standard Deviation 8513.34
Change From Baseline in CD40L at 3 Months Change in CD40L from Baseline at 3 Months	2559.09 pg/mL Standard Deviation 9936.68	-3857.02 pg/mL Standard Deviation 6972.17

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Matrix metalloproteinase-9 (MMP-9) measured using enzyme linked immunosorbent assay (ELISA)

Outcome measures

Measure	Sildenafil Period n=16 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in MMP-9 at 3 Months MMP-9 at Baseline	441.00 ng/mL Standard Deviation 399.32	454.85 ng/mL Standard Deviation 298.36
Change From Baseline in MMP-9 at 3 Months Change in MMP-9 from Baseline at 3 Months	-5.61 ng/mL Standard Deviation 437.21	-105.65 ng/mL Standard Deviation 333.04

SECONDARY outcome

Timeframe: Baseline and After 3 months of Study Drug use (i.e., either at 3 months pre-washout or at 6 months, depending on group assignment)

Population: Pre-specified linear mixed model statistical analysis not conducted because not scientifically appropriate due to insufficient enrollment. The number of participants analyzed reflects those in each period who had evaluable data for the given outcome measure at both the Baseline and After 3 months of Study Drug use timepoints.

Myeloperoxidase (MPO) measured using enzyme linked immunosorbent assay (ELISA)

Outcome measures

Measure	Sildenafil Period n=16 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=19 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Change From Baseline in MPO at 3 Months MPO at Baseline	236.68 ng/mL Standard Deviation 276.33	233.24 ng/mL Standard Deviation 241.29
Change From Baseline in MPO at 3 Months Change in MPO from Baseline at 3 Months	17.18 ng/mL Standard Deviation 242.20	-54.04 ng/mL Standard Deviation 309.70

SECONDARY outcome

Timeframe: 6 Months and 2 Weeks from Baseline Visit

SAEs include death, hospitalization or prolonged existing hospitalization, life threatening, persistent or significant disability, birth defect/congenital anomaly, or medically significant event.

Outcome measures

Measure	Sildenafil Period n=25 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=25 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Serious Adverse Events (SAE)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 Months and 2 Weeks from Baseline Visit

AEs related to sildenafil treatment may include headache, flushing, indigestion, or visual disturbance, among others.

Outcome measures

Measure	Sildenafil Period n=25 Participants Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=25 Participants Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Adverse Events (AE) Related to Treatment	3 Participants	3 Participants

Adverse Events

Sildenafil Period

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Period

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Sildenafil Period n=25 participants at risk Participants who received Sildenafil 50 mg once daily in either the first or last 3 months of the study	Placebo Period n=25 participants at risk Participants who received Placebo tablets (matching Sildenafil 50 mg) once daily in either the first or last 3 months of the study
Musculoskeletal and connective tissue disorders Back pain	4.0% 1/25 • Number of events 1 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.	0.00% 0/25 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.
Nervous system disorders Headache	4.0% 1/25 • Number of events 1 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.	0.00% 0/25 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.
Nervous system disorders Insomnia	4.0% 1/25 • Number of events 1 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.	0.00% 0/25 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.
Musculoskeletal and connective tissue disorders Joint Pain	0.00% 0/25 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.	4.0% 1/25 • Number of events 1 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/25 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.	4.0% 1/25 • Number of events 1 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/25 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.	4.0% 1/25 • Number of events 1 • Adverse event data were collected over the entire study duration for each participant (i.e., 6 months and 2 weeks). The definition of adverse event and/or serious adverse event did not differ from the clinicaltrials.gov definitions.

Additional Information

Kimberly P. Liang, MD, MS

University of Pittsburgh

Phone: 412-586-3550

Email: liangkp@upmc.edu

Results disclosure agreements

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