Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Rare Diseases

Neoplasm Metastasis

Ischemia

Sclerosis

Scleroderma, Systemic

Scleroderma, Diffuse

Raynaud Disease

Neoplastic Processes

Connective Tissue Diseases

Skin Diseases

Vascular Diseases

Livedoid Vasculopathy

Thrombosis

Embolism

Embolism and Thrombosis

Peripheral Arterial Disease

Peripheral Vascular Diseases

Skin Diseases, Vascular

Systemic Scleroderma

Vasodilator Agents

Platelet Aggregation Inhibitors

All Drugs and Chemicals

Iloprost

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.

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.

Placebo IV infusion

Iloprost Injection, for intravenous use

Wade Benton, Pharm D

This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of iloprost on the frequency of and relief from symptomatic digital ischemic episodes in subjects with systemic sclerosis.

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

A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study Evaluating the Safety and Efficacy of Intravenous Iloprost in Subjects With Systemic Sclerosis Experiencing Symptomatic Digital Ischemic Episodes (AURORA Study)

The primary efficacy parameter is the change in the weekly frequency of symptomatic RP attacks from baseline

Eicos Sciences, Inc.

Antihypertensive Agents

Selexipag

Selexipag is initiated at 200 µg twice daily (b.i.d.) and up-titrated every 3 days in 200 μg b.i.d. increments up to the maximum tolerated dose (MTD) for each individual patient but not above 1600 µg during the 3-week titration phase. This is followed by a 5-week maintenance phase, during which patients continue the treatment at their individual MTD.

Placebo matching selexipag tablets is administered according to the same schedule as selexipag

Film-coated tablets containing 200 μg of selexipag to be administered orally twice daily

Placebo matching selexipag 200 μg tablets to be administered orally twice daily

Placebo

Ralph Preiss, MD

The primary objective of the study is to determine the activity of selexipag on Raynaud attack frequency in subjects with Raynaud's Phenomenon (RP) secondary to Systemic Sclerosis (SSc).

Effects of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis

A Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel Group, Exploratory Phase 2 Study to Assess Efficacy and Safety of Selexipag in Adult Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis

QOL is assessed by the Scleroderma Health Assessment Questionnaire (SHAQ)

The number of RP attacks is determined from daily entries in electronic Diaries (eDiary).

A treatment-emergent adverse event is any adverse event (AE) temporally associated with the use of a study treatment, whether or not considered related to the study treatment, including any abnormalities in ECG parameters, vital signs or laboratory tests

Actelion

Immune System Diseases

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Hypersensitivity

Respiratory Tract Infections

APD791

Serotonin

Neurotransmitter Agents

Participants will receive a single oral dose of temanogrel during the treatment visit.

Temanogrel

Participants will receive a single oral dose of temanogrel matching placebo during the treatment visit.

Pfizer CT.gov Call Center

The purpose of this study is to determine whether oral temanogrel improves digital blood flow in participants with Raynaud's phenomenon secondary to systemic sclerosis (SSc-RP) as a potential safe and effective treatment for symptoms associated with SSc-RP.

The study will be conducted in 2 stages: Stage A and Stage B. In both stages, participants will be equally randomized in a double-blind manner to a 3-period crossover treatment sequence. Separate cohorts of participants will participate in each stage. In Stage A, participants will be treated with two dose levels of temanogrel and placebo. Doses in Stage B will be determined based on the results of Stage A.

A Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Adult Participants With Raynaud's Phenomenon Secondary to Systemic Sclerosis

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Area under the curve for rewarming of digital blood flow after 30 minutes following a cold challenge was assessed. Area under the curve was defined as the area under the skin temperature curve and rewarming was a delicate phase of therapeutic hypothermia (TH). A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Rewarming was assessed by infrared (IR) thermography which was an indirect method for evaluation of blood flow based on imaging skin temperature. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

Area under the curve for reperfusion of digital blood flow after 30 minutes following a cold challenge was assessed. A cold challenge was conducted by immersing hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Reperfusion was assessed with laser speckle contrast imaging (LSCI) which was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu (and also pu\*seconds) are considered better in the context of this trial. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu are considered better in the context of this trial. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Changes in skin temperature at each visit were imaged IR thermography. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. Changes in skin temperature at each visit were imaged using LSCI. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu are considered better in the context of this trial. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

AUC was defined as the area under the skin temperature curve. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu (and also pu\*seconds) are considered better in the context of this trial. AUC was defined as the area under the skin temperature curve, based on the LSCI results. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. Slope was calculated based on the changes in skin temperature imaged using LSCI and IR thermography during the initial 120 seconds following the cold challenge. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu (and also pu/seconds) are considered better in the context of this trial. Slope was calculated based on the changes in skin temperature imaged using LSCI during the initial 120 seconds following the cold challenge. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments. If 50% recovery was not achieved, the recovery time was set to 30 minutes. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments. If 70% recovery was not achieved, the recovery time was set to 30 minutes. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room temperature. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room temperature. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu are considered better in the context of this trial. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

The distal dorsal difference was defined as the difference in temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room temperature. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room temperature. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu are considered better in the context of this trial. The distal dorsal difference was defined as the difference in perfusion temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

An adverse event was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect.

Arena is a wholly owned subsidiary of Pfizer

Pfizer

Participants received temanogrel 120 mg in the study.

Temanogrel 120 mg

Participants received temanogrel 60 mg in this study.

Temanogrel 60 mg

Participants received placebo in the study.

Participants received oral temanogrel 120 milligram (mg) (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 1. Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days.

Temanogrel 120 mg Then Temanogrel 60 mg Then Placebo

Participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 1. Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days.

Temanogrel 120 mg Then Placebo Then Temanogrel 60mg

Participants received temanogrel 60 mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally during treatment period 1 (B). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of period 2. Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days.

Temanogrel 60 mg Then Temanogrel 120 mg Then Placebo

Participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally during treatment period 1 (B). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 3. Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days.

Temanogrel 60 mg Then Placebo Then Temanogrel 120 mg

Participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of period 2. Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received temanogrel 60 mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days.

Placebo Then Temanogrel 120 mg Then Temanogrel 60 mg

Participants received placebo matched to temanogrel capsules (6 capsules) once orally (C). Period 1 was followed by treatment period 2. On Day 1 of treatment period 2, participants received temanogrel 60mg (3 temanogrel capsules of 20 mg each and 3 capsules of placebo) once orally (B). Period 2 was followed by treatment period 3. On Day 1 of treatment period 3, participants received oral temanogrel 120 mg (6 temanogrel capsules of 20 mg) once per treatment visit (A) orally once on Day 1 of treatment period 3. Study treatment administrations between two periods were separated by washout period of at least 72 hours to 7 days.

Placebo Then Temanogrel 60 mg Then Temanogrel 120 mg

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The full analysis set (FAS) included all randomized participants, irrespective of whether they received any study treatment.

This study was terminated early due to a business decision that was not due to any safety concerns. The number of participants was smaller than originally planned and only summary statistics were therefore generated for primary and secondary outcome measures.

Pfizer ClinicalTrials.gov Call Center

Participants received placebo in this study.

FAS included all randomized participants, irrespective of whether they received any study treatment.

Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge

Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty Minutes Following a Cold Challenge

Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography

Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI)

Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography

Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI

FAS included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.

AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography

Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI

Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography

Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI

IR thermography

LSCI

Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI

Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI

Change From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography

Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI

Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography

Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI

TEAEs

Serious TEAEs

Participants received temanogrel 60 mg in the study.

Safety set included all randomized participants who received at least one dose of study treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)	NCT04040322	Raynaud's Pheno...	Placebo IV infu... Iloprost Inject...	18 Years -	Eicos Sciences, Inc.
Effects of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis	NCT02260557	Raynaud's Pheno...	Selexipag Placebo	18 Years -	Actelion
Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)	NCT04040322	Raynaud's Pheno...	Placebo IV infu... Iloprost Inject...	18 Years -	Eicos Sciences, Inc.
A Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Adult Participants With Raynaud's Phenomenon Secondary to Systemic Sclerosis	NCT04915950	Raynaud's Pheno...	Temanogrel Placebo	18 Years - 75 Years	Pfizer
Intravenous Iloprost in Subjects With Symptomatic Raynaud's Phenomenon Secondary to Systemic Sclerosis (Phase 3)	NCT04040322	Raynaud's Pheno...	Placebo IV infu... Iloprost Inject...	18 Years -	Eicos Sciences, Inc.
Effects of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis	NCT02260557	Raynaud's Pheno...	Selexipag Placebo	18 Years -	Actelion

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