Trial Outcomes & Findings for Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV (NCT NCT00596752)

Last Updated: 2018-04-04

Results Overview

The assessment of ulcer area was collected per lesion with up to 2 lesions per subject (both legs could be affected). In the analysis a subject is only considered completely healed at a time point, if all ischemic lesions are reported as completely healed at that time point.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

840 participants

Primary outcome timeframe

At 12 weeks after the end of study drug treatment

Results posted on

2018-04-04

Participant Flow

This study started to enroll subjects in March 2004 in order to end up with 840 enrolled subjects. The study was conducted using a two-stage group sequential adaptive design with possible sample size adjustment after the planned interim analysis, which was performed after stage 1. After the interim analysis subjects were included in stage 2.

Participant Flow refers to the Randomized Set (RS). RS consists of all subjects randomized into the study who have completed the study or terminated prematurely.

Participant milestones

Participant milestones
Measure	Alprostadil Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Overall Study STARTED	415	425
Overall Study Randomized and Treated	415	424
Overall Study COMPLETED	289	282
Overall Study NOT COMPLETED	126	143

Reasons for withdrawal

Reasons for withdrawal
Measure	Alprostadil Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Overall Study Other Reason	44	49
Overall Study Adverse Event	34	34
Overall Study Lost to Follow-up	22	38
Overall Study Withdrawal by Subject	12	9
Overall Study Unsatisfactory Compliance	9	6
Overall Study Lack of Efficacy	4	7
Overall Study Protocol Violation	1	0

Baseline Characteristics

Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alprostadil n=416 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=423 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Total n=839 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	153 Participants n=5 Participants	170 Participants n=7 Participants	323 Participants n=5 Participants
Age, Categorical >=65 years	263 Participants n=5 Participants	253 Participants n=7 Participants	516 Participants n=5 Participants
Age, Continuous	66.8 years STANDARD_DEVIATION 8.5 • n=5 Participants	66.4 years STANDARD_DEVIATION 9.3 • n=7 Participants	66.6 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	117 Participants n=7 Participants	240 Participants n=5 Participants
Sex: Female, Male Male	293 Participants n=5 Participants	306 Participants n=7 Participants	599 Participants n=5 Participants
Weight	75.4 kilogram (kg) STANDARD_DEVIATION 11.9 • n=5 Participants	76.6 kilogram (kg) STANDARD_DEVIATION 12.6 • n=7 Participants	76.0 kilogram (kg) STANDARD_DEVIATION 12.2 • n=5 Participants

PRIMARY outcome

Timeframe: At 12 weeks after the end of study drug treatment

Population: Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) in case of missing values. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.

Outcome measures

Outcome measures
Measure	Alprostadil n=414 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=424 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Complete Healing of Ischemic Necroses and Ulcerations at 12 Weeks After the End of Study Drug Treatment Stage 1 (n=253, n=251)	49 participants	43 participants
Complete Healing of Ischemic Necroses and Ulcerations at 12 Weeks After the End of Study Drug Treatment Stage 2 (n=161, n=173)	27 participants	30 participants

PRIMARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Assessment of amputations was collected per leg affected by a lesion with up to 2 lesions per subject. Amputations were regarded as major if they were performed at the ankle joint level or above. Amputations of toes or part of the foot leaving a stump thereon the subject can walk were regarded as minor. An affected leg is defined as a leg with at least 1 lesion on Study Day -6 to -2 and only amputations of affected legs are considered in the efficacy analysis of amputations. A subject is counted as major/minor amputated, if at least 1 affected leg was major/minor amputated.

Outcome measures

Outcome measures
Measure	Alprostadil n=414 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=424 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Occurrence of Major Amputations at 24 Weeks After the End of Study Drug Treatment Stage 1 (n=253, n=251)	32 participants	49 participants
Occurrence of Major Amputations at 24 Weeks After the End of Study Drug Treatment Stage 2 (n=161, n=173)	20 participants	13 participants

SECONDARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Population: Of the 838 subjects in the Full Analysis Set (FAS), 568 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.

Outcome measures

Outcome measures
Measure	Alprostadil n=289 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=279 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Complete Healing of Ischemic Necroses and Ulcerations at 24 Weeks After the End of Study Drug Treatment	108 participants	103 participants

SECONDARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Visit values of intensity of rest pain from a visual analogue scale, ranging from 0 mm (no pain) to 100 mm (maximum conceivable pain), had to be reported in the case of presence of rest pain only. If the leading question in regard to the presence of rest pain is answered with "No" and no visit value is specified, the visit value will be set to 0 for the analysis.

Outcome measures

Outcome measures
Measure	Alprostadil n=414 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=424 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Intensity of Rest Pain Induced by Ischemic Lesions at 24 Weeks After the End of Study Drug Treatment	17.57 millimeters (mm) Standard Deviation 25.33	16.38 millimeters (mm) Standard Deviation 25.08

SECONDARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Population: Of the 838 subjects in the Full Analysis Set (FAS), 465 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.

In case of two ulcers the worse ulcer status is analyzed. The categories of investigator assessment are: complete healing, decrease by ≥ 50 %, unchanged, increase by ≥ 50 %.

Outcome measures

Outcome measures
Measure	Alprostadil n=233 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=232 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment Complete healing	101 participants	98 participants
Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment Decrease by >= 50 %	57 participants	56 participants
Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment Remains unchanged	45 participants	48 participants
Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment Increase by >= 50 %	30 participants	30 participants

SECONDARY outcome

Timeframe: During the course of the study (up to 196 days)

Population: Full Analysis Set (FAS) consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.

The number of subjects who used analgesics are summarized for different time points/intervals during the course of the study.

Outcome measures

Outcome measures
Measure	Alprostadil n=414 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=424 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Week 2 (n=409, n=422)	292 participants	308 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Week 3 (n=399, n=416)	259 participants	284 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Week 4 (n=393, n=404)	238 participants	257 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 29-42 (n=348, n=354)	170 participants	191 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 141-168 (n=306, n=304)	118 participants	109 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 169-196 (n=272, n=271)	98 participants	90 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Prior to treatment (n=414, n=424)	300 participants	318 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 1 (n=414, n=424)	292 participants	314 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 2 (n=414, n=424)	295 participants	313 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 3 (n=413, n=424)	295 participants	317 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 4 (n=412, n=423)	292 participants	316 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 5 (n=411, n=423)	294 participants	311 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 6 (n=411, n=423)	290 participants	312 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Concomitant, Study Day 7 (n=409, n=422)	290 participants	306 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 43-56 (n=361, n=370)	164 participants	173 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 57-70 (n=361, n=346)	155 participants	155 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 71-84 (n=352, n=344)	146 participants	148 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 85-98 (n=341, n=339)	143 participants	140 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 99-112 (n=321, n=318)	132 participants	127 participants
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) Post treatment, Study Days 113-140 (n=309, n=301)	122 participants	117 participants

SECONDARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Systolic pressure at ankle level was measured at the Arteria tibialis posterior and the Arteria dorsalis pedis. Two individual series of measurements of arterial pressures per subject across the assessed visits were selected for the analysis. For the first analysis (worst change analysis) the series of measurements in the one artery which has the worst change from Baseline at the final measurement was used. For the second analysis (worst value analysis) the series of measurements which has the worst final post-Baseline measurement was used. The series relevant for the analyses was selected from the series for the affected leg or legs only. The selection is 1 out of up to 4 series available per subject. Series without Baseline value and series with at least 1 measurement of more than 150 mmHg were excluded from the selection process due to the suspicion of media sclerosis of the lower limb artery.

Outcome measures

Outcome measures
Measure	Alprostadil n=383 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=394 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Systolic Pressure at Ankle Level at 24 Weeks After the End of Study Drug Treatment Worst value analysis	39.39 mmHg Standard Deviation 29.92	36.45 mmHg Standard Deviation 27.19
Systolic Pressure at Ankle Level at 24 Weeks After the End of Study Drug Treatment Worst change analysis	42.83 mmHg Standard Deviation 30.16	39.47 mmHg Standard Deviation 28.32

SECONDARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Population: Of the 838 subjects in the Full Analysis Set (FAS), 613 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.

Outcome measures

Outcome measures
Measure	Alprostadil n=316 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=297 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Minor Amputations at 24 Weeks After the End of Study Drug Treatment	65 participants	40 participants

SECONDARY outcome

Timeframe: At 24 weeks after the end of study drug treatment

Population: Of the 838 subjects in the Full Analysis Set (FAS), 577 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.

The number of subjects with revascularization prior to or at 24 weeks after the end of study drug treatment is presented below.

Outcome measures

Outcome measures
Measure	Alprostadil n=294 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=283 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Revascularization Procedures at 24 Weeks After the End of Study Drug Treatment	6 participants	7 participants

SECONDARY outcome

Timeframe: During the course of the study (up to 196 days)

Population: Safety Set consists of all randomized subjects who received at least one dose of trial medication.

Outcome measures

Outcome measures
Measure	Alprostadil n=416 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=423 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
All-cause Mortality During the Course of the Study (up to 196 Days)	20 participants	15 participants

SECONDARY outcome

Timeframe: During the course of the study (up to 196 days)

Population: Safety Set consists of all randomized subjects who received at least one dose of trial medication.

Outcome measures

Outcome measures
Measure	Alprostadil n=416 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=423 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Cardiovascular Mortality During the Course of the Study (up to 196 Days)	11 participants	14 participants

SECONDARY outcome

Timeframe: During the course of the study (up to 196 days)

Population: Safety Set consists of all randomized subjects who received at least one dose of trial medication.

Cardiovascular morbidity is presented as number of subjects with myocardial infarction and/or stroke during the course of the study.

Outcome measures

Outcome measures
Measure	Alprostadil n=416 Participants Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=423 Participants Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Cardiovascular Morbidity During the Course of the Study (up to 196 Days) Myocardial infarctions	5 participants	6 participants
Cardiovascular Morbidity During the Course of the Study (up to 196 Days) Strokes	3 participants	3 participants

Adverse Events

Alprostadil

Serious events: 87 serious events

Other events: 61 other events

Deaths: 0 deaths

Placebo

Serious events: 62 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Alprostadil n=416 participants at risk Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Alprostadil: - Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion	Placebo n=423 participants at risk Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks. Placebo: - Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion
Skin and subcutaneous tissue disorders SKIN ULCER	5.8% 24/416 • Number of events 29 • Adverse Events were collected during the course of the study from Study Day 0 up to Study Day 196. Adverse Events refer to the Safety Set. Safety Set consists of all subjects who have completed the study or terminated prematurely and who have received at least 1 dose of study medication.	6.1% 26/423 • Number of events 28 • Adverse Events were collected during the course of the study from Study Day 0 up to Study Day 196. Adverse Events refer to the Safety Set. Safety Set consists of all subjects who have completed the study or terminated prematurely and who have received at least 1 dose of study medication.
Vascular disorders PERIPHERAL ISCHAEMIA	9.6% 40/416 • Number of events 41 • Adverse Events were collected during the course of the study from Study Day 0 up to Study Day 196. Adverse Events refer to the Safety Set. Safety Set consists of all subjects who have completed the study or terminated prematurely and who have received at least 1 dose of study medication.	9.7% 41/423 • Number of events 45 • Adverse Events were collected during the course of the study from Study Day 0 up to Study Day 196. Adverse Events refer to the Safety Set. Safety Set consists of all subjects who have completed the study or terminated prematurely and who have received at least 1 dose of study medication.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1 877 822 9493 (UCB)

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60