Trial Outcomes & Findings for Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3) (NCT NCT04040322)

Last Updated: 2025-05-25

Results Overview

The primary efficacy parameter is the change in the weekly frequency of symptomatic RP attacks from baseline. The baseline weekly frequency of symptomatic RP attacks was defined as the average number of weekly symptomatic RP attacks that occurred during the 10- to 25-day baseline ePRO diary completion period. The double-blind endpoint weekly frequency of symptomatic RP attacks was defined as the average number of weekly symptomatic RP attacks that occurred during Days 8 to 21, inclusive

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

198 participants

Primary outcome timeframe

From baseline (Day 10 to Day 25 of screening period) to the end ofthe efficacy follow-up (Day 8 to Day 21).

Results posted on

2025-05-25

Participant Flow

The study was initiated on 14 October 2019 and completed on 07 May 2021. It was conducted in 31 sites located in the United States.

In this study 258 participants with Systemic Sclerosis (SSc) were screened.198 participants who had at least 10 symptomatic Raynaud's phenomenon (RP) attacks on the 5-day eligibility period were randomized: 98 to the placebo arm and 100 to the Iloprost arm. Two participants stopped the study prior to receiving any treatment. The number of participants who were randomized and started the treatment was 97 in the placebo arm and 99 in the Iloprost arm.

Participant milestones

Participant milestones
Measure	Placebo Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Overall Study STARTED	97	99
Overall Study COMPLETED	97	99
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=97 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Total n=196 Participants Total of all reporting groups
Age, Continuous	52.0 years STANDARD_DEVIATION 10.92 • n=99 Participants	52.4 years STANDARD_DEVIATION 13.59 • n=107 Participants	52.2 years STANDARD_DEVIATION 12.31 • n=206 Participants
Sex: Female, Male Female	86 Participants n=99 Participants	88 Participants n=107 Participants	174 Participants n=206 Participants
Sex: Female, Male Male	11 Participants n=99 Participants	11 Participants n=107 Participants	22 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=99 Participants	12 Participants n=107 Participants	22 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	86 Participants n=99 Participants	85 Participants n=107 Participants	171 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Asian	5 Participants n=99 Participants	2 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	9 Participants n=99 Participants	6 Participants n=107 Participants	15 Participants n=206 Participants
Race (NIH/OMB) White	80 Participants n=99 Participants	87 Participants n=107 Participants	167 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Phosphodiesterase-5 (PDE5) Inhibitors at Screening Yes	37 Participants n=99 Participants	40 Participants n=107 Participants	77 Participants n=206 Participants
Phosphodiesterase-5 (PDE5) Inhibitors at Screening No	60 Participants n=99 Participants	59 Participants n=107 Participants	119 Participants n=206 Participants
Weekly frequency of symptomatic RP attacks at baseline	28.63 Weekly frequency of RP attacks STANDARD_DEVIATION 18.113 • n=99 Participants	32.49 Weekly frequency of RP attacks STANDARD_DEVIATION 26.393 • n=107 Participants	30.58 Weekly frequency of RP attacks STANDARD_DEVIATION 22.701 • n=206 Participants

PRIMARY outcome

Timeframe: From baseline (Day 10 to Day 25 of screening period) to the end ofthe efficacy follow-up (Day 8 to Day 21).

Population: The Intention-To-Treat (ITT) Population was defined as all randomized patients who initiated (received) study drug infusion.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Change in Frequency of Symptomatic RP Attacks	-11.47 Number of RP attacks per week Interval -13.69 to -9.25	-12.73 Number of RP attacks per week Interval -14.92 to -10.55

SECONDARY outcome

Timeframe: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).

Population: The ITT-To-Treat (ITT) population, defined as all randomized patients who initiated (received) study drug infusion.

Change in overall severity of RP attack symptoms as registered in electronic diary. It was measured using an 11-point numeric rating scale (NRS) as follows: 0 = no pain/numbness/tingling/discomfort, 1 to 3 = mild pain/numbness/tingling/discomfort, 4 to 6 = moderate pain/numbness/tingling/discomfort, and 7 to 10 = severe pain/numbness/tingling/discomfort. The severity of the symptoms (pain, numbness, discomfort or tingling) was rated by the patient in the electronic diary (ePRO). The symptom with the worst average baseline value for each patient was compared to the average severity rate of that symptom which occurred during Days 8 to 21 of the treatment period. If more than 1 symptom had the same value, the symptom used for analysis was based on the following order of rank: pain\>numbness\>tingling\>discomfort.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Change in Severity of RP Attack Symptoms	-2.13 Score on a scale Interval -2.51 to -1.75	-2.19 Score on a scale Interval -2.57 to -1.82

SECONDARY outcome

Timeframe: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).

The weekly duration is calculated as the average duration of a systematic RP attack times weekly frequency, as registered in electronic diary. The baseline weekly duration was calculated as the average duration of a systematic RP attack times weekly frequency during the 10- to 25-day baseline electronic diary completion period. The end of the efficacy follow-up weekly duration of symptomatic RP attacks is calculated as the average duration of a systematic RP attack times weekly frequency during Days 8 to 21, inclusive.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Weekly Total Duration of Symptomatic RP Attacks.	-321.04 Minutes Interval -385.03 to -257.05	-326.48 Minutes Interval -389.53 to -263.44

SECONDARY outcome

Timeframe: From baseline (Day 10 to Day 25 of screening period) to the end of the efficacy follow-up (Day 8 to Day 21).

The responders are defined as participants that have at least 50% reduction in weekly total duration of symptomatic RP attacks and at least 50% reduction in overall severity from baseline. Duration of symptomatic RP attacks and severity of attacks are obtained from electronic diary.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 Participants Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Percentage of Responders	33 Participants	33 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 78 other events

Deaths: 0 deaths

Iloprost Injection, for Intravenous Use

Serious events: 1 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=97 participants at risk Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 participants at risk Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/97 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	1.0% 1/99 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Injury, poisoning and procedural complications Limb traumatic amputation	0.00% 0/97 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	1.0% 1/99 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).

Other adverse events

Additional Information

Chief Executive Officer

CiVi Biopharma, Inc.

Phone: 301-968-2390

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=97 participants at risk Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Placebo IV infusion: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.	Iloprost Injection, for Intravenous Use n=99 participants at risk Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line. Study drug will be initiated at a starting dose 0.5 ng/kg/min up to 2.0 ng/kg/min. Iloprost Injection, for intravenous use: Study drug will be initiated at a starting dose of 0.5 ng/kg/min up to 2.0 ng/kg/min. Subjects will receive study drug for 5 consecutive days as an IV infusion over 6 hours each day via a peripheral line.
Nervous system disorders Headache	39.2% 38/97 • Number of events 82 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	85.9% 85/99 • Number of events 271 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Nervous system disorders Dizziness	10.3% 10/97 • Number of events 14 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	10.1% 10/99 • Number of events 16 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Nervous system disorders Head discomfort	5.2% 5/97 • Number of events 11 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	2.0% 2/99 • Number of events 5 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Nervous system disorders Paraesthesia	5.2% 5/97 • Number of events 8 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	1.0% 1/99 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Gastrointestinal disorders Nausea	15.5% 15/97 • Number of events 30 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	57.6% 57/99 • Number of events 104 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Gastrointestinal disorders Vomiting	5.2% 5/97 • Number of events 5 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	24.2% 24/99 • Number of events 32 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Gastrointestinal disorders Diarrhoea	9.3% 9/97 • Number of events 9 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	13.1% 13/99 • Number of events 20 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
General disorders Fatigue	9.3% 9/97 • Number of events 11 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	15.2% 15/99 • Number of events 21 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
General disorders Infusion site pain	6.2% 6/97 • Number of events 6 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	15.2% 15/99 • Number of events 18 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
General disorders Infusion site erythema	4.1% 4/97 • Number of events 4 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	5.1% 5/99 • Number of events 5 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
General disorders Asthenia	2.1% 2/97 • Number of events 2 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	5.1% 5/99 • Number of events 5 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
General disorders Infusion site extravasation	1.0% 1/97 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	6.1% 6/99 • Number of events 6 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
General disorders Chills	1.0% 1/97 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	5.1% 5/99 • Number of events 7 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Musculoskeletal and connective tissue disorders Pain in jaw	4.1% 4/97 • Number of events 7 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	27.3% 27/99 • Number of events 58 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Musculoskeletal and connective tissue disorders Pain in extremity	4.1% 4/97 • Number of events 4 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	6.1% 6/99 • Number of events 11 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Musculoskeletal and connective tissue disorders Myalgia	5.2% 5/97 • Number of events 5 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	4.0% 4/99 • Number of events 9 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Skin and subcutaneous tissue disorders Skin ulcer	12.4% 12/97 • Number of events 22 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	11.1% 11/99 • Number of events 16 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Vascular disorders Flushing	7.2% 7/97 • Number of events 21 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	28.3% 28/99 • Number of events 48 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).
Cardiac disorders Palpitations	5.2% 5/97 • Number of events 8 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).	0.00% 0/99 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit, Visit 9, at day 35 (+7 days). For this study, hypotension will be considered an adverse event of special interest (AESI).