A Research Study to Show the Effect of Aprocitentan in th... | NCT03541174 | Trialant
NCT03541174
Sponsor
Idorsia Pharmaceuticals Ltd.
Status
Completed
Last Update Posted
Mar 21, 2023Actual
Enrollment
730Actual
Phase
Phase 3
Conditions
Resistant Hypertension
Interventions
Aprocitentan 12.5 mg
Aprocitentan 25 mg
Placebo
Countries
United States
Australia
Belgium
Canada
China
Czechia
Finland
France
Germany
Greece
Hungary
Israel
Italy
Lithuania
Netherlands
Poland
Russia
Spain
Ukraine
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03541174
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ID-080A301
Secondary IDs
ID
Type
Description
Link
2017-004393-33
EudraCT Number
Brief Title
A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety
Official Title
Multi-center, Blinded, Randomized, Parallel-group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension (RHT)
Acronym
PRECISION
Organization
Idorsia Pharmaceuticals Ltd.INDUSTRY
Status Module
Record Verification Date
Mar 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 18, 2018Actual
Primary Completion Date
May 14, 2021Actual
Completion Date
Apr 25, 2022Actual
First Submitted Date
May 17, 2018
First Submission Date that Met QC Criteria
May 29, 2018
First Posted Date
May 30, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Nov 8, 2022
Results First Submitted that Met QC Criteria
Mar 16, 2023
Results First Posted Date
Mar 21, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Mar 16, 2023
Last Update Posted Date
Mar 21, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Idorsia Pharmaceuticals Ltd.INDUSTRY
Collaborators
Name
Class
Janssen Biotech, Inc.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The goal of this clinical trial is to show the blood pressure lowering effect of aprocitentan, a new drug, when added to other anti-hypertensive drugs of patients with difficult to control (resistant) high blood pressure (hypertension), and to show that blood pressure reduction is kept for long period of time.
Detailed Description
Participation in the study will be up to 68 weeks.
The study has 4 periods:
Screening period
Placebo run-in period
Randomized treatment period
Safety follow-up period
The screening period lasts between 4 and 12 weeks. It starts at the screening visit with the signing of the informed consent form (ICF) and ends the day before the participant enters the run-in period.
At least 4 weeks before the start of the run-in period, the background antihypertensive medication (except beta-blockers) of participants with a diagnosis of true resistant hypertension and having a mean trough sitting systolic blood pressure of equal to or greater than 140 mmHg measured by automated AOBPM will be standardized by switching to a fixed combination of a calcium channel blocker (amlodipine), an angiotensin receptor blocker (valsartan) and a diuretic (hydrochlorothiazide).
In case a beta-blocker is used as one of the background antihypertensive medications or for any other indication, this can be kept, with the provision that it has been initiated and the dose kept stable for at least 4 weeks prior to the screening visit and the dose kept stable until the end-of-treatment.
Following the screening period this study has a run-in period of 4 weeks. During this period, placebo will be administered in order to exclude potential placebo responders.
Following the run-in period eligible participants will enter the randomized treatment period. This period lasts for 48 weeks. It starts at randomization (i.e., Day 1 of the double-blind part) and ends at the end-of-treatment visit (i.e., at the end of the double-blind withdrawal part).
The randomized treatment period consists of 3 parts: Part 1 is double-blind, randomized, parallel-group and placebo-controlled and lasts 4 weeks. Part 2 is single-blind and single-arm and lasts for 32 weeks. Part 3 is a double-blind withdrawal, randomized, parallel-group and placebo-controlled and lasts for 12 weeks.
End-of treatment is at Week 48 (i.e., end of the double-blind withdrawal part). The safety follow-up starts on the day after the last dose of study treatment and ends 30 to 33 days after the last dose of study treatment.
Conditions Module
Conditions
Resistant Hypertension
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
730Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Aprocitentan 25 mg in Part 1 (double-blind)
Experimental
Participants will receive aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
Drug: Aprocitentan 25 mg
Aprocitentan 12.5 mg in Part 1 (double-blind)
Experimental
Participants will receive aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
Drug: Aprocitentan 12.5 mg
Placebo in Part 1 (double-blind)
Placebo Comparator
Participants will receive placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Drug: Placebo
Aprocitentan 25 mg in Part 2 (single-blind, single arm)
Experimental
After 4-weeks in the double-blind randomized part (Part 1), participants will received 25 mg aprocitentan, orally, once daily in the morning for 32 weeks.
Drug: Aprocitentan 25 mg
Aprocitentan 25 mg in Part 3 (double-blind withdrawal)
Experimental
After 32-weeks in the single-blind, single-arm part (Part 2), participants will be re-randomized and receive aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Aprocitentan 12.5 mg
Drug
Tablet, oral use
Aprocitentan 12.5 mg in Part 1 (double-blind)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Automated Office Blood Pressure Measurement
Changes from baseline to Week 4 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.
Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
Secondary Outcomes
Measure
Description
Time Frame
Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Unattended Automated Office Blood Pressure Measurement
Changes from double-blind withdrawal baseline (Week 36) to Week 40 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Screening period:
Signed and dated informed consent form (ICF) prior to any study-mandated procedure;
Male and female participants; 18 years (or year of country specific majority) or older;
Historical documentation in the participant's medical records on uncontrolled blood pressure despite at least 3 background antihypertensive medications within 1 year before screening visit;
Treated with at least 3 antihypertensive therapies of different pharmacological classes for at least 4 weeks before the screening visit (Visit 1);
Mean Sitting Systolic Blood Pressure (SiSBP) greater or equal to 140 mmHg measured by Automated Office Blood Pressure Measurement (AOBPM);
Women of childbearing potential are eligible only if the following applies:
Negative pregnancy test at screening and at baseline (i.e., before randomization);
Agreement to undertake pregnancy tests during the study and up to 30 days after randomized study treatment discontinuation;
Agreement to use methods of birth control from Screening up to at least 30 days after randomized study treatment discontinuation.
Run-in period (RI):
Switched to the standardized background antihypertensive therapy at least 4 weeks before the first RI visit;
Mean trough SiSBP greater than or equal to140 mmHg as measured by AOBPM.
Randomization period:
Stable dose of the standardized background antihypertensive therapy for at least 1 week before the end of the RI period;
Mean trough SiSBP greater than or equal to 140 mmHg measured by AOBPM.
Exclusion Criteria:
Apparent/pseudo Resistant Hypertension (RHT) due to white coat effect, medical inertia, poor therapeutic adherence, or secondary causes of hypertension (except sleep apnea);
Confirmed severe hypertension (grade 3) defined as SiSBP greater than or equal to 180 mmHg and/or Sitting Diastolic Blood Pressure (SiDBP) greater than or equal to 110 mmHg as measured by AOBPM at two different timepoints;
Pregnant or lactating participants;
Clinically significant unstable cardiac disease at screening or in the past in the opinion of the investigator (exclusion of participants with significant or potential unstable cardiac disease);
Severe renal insufficiency;
Any known factor, disease or clinically relevant medical or surgical conditions that, in the opinion of the investigator, might put the participant at risk, interfere with treatment compliance, study conduct or interpretation of the results.
Treatment with any medication which may affect blood pressure (BP) and/or treatment with high dose of loop diuretics (i.e., furosemide greater than 80 mg/day, or equivalent dosage of other loop diuretics).
730 participants are considered to be enrolled in the study and were randomized to study treatment.
Recruitment Details
The study was done from 18 June 2018 to 25 April 2022.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Aprocitentan 12.5 mg in Part 1 (Double-blind)
Participants were randomized and received aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
FG001
Aprocitentan 25 mg in Part 1 (Double-blind)
Periods
Title
Milestones
Reasons Not Completed
Part 1 Double-Blind
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol: Protocol
Feb 27, 2020
Nov 8, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Denmark
South Korea
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Study with multiple periods and parts.
Once eligibility is confirmed during screening and the run-in period, the individuals entered the randomized treatment period consisting of 3 parts: Part 1: double-blind (DB), randomized to aprocitentan 12.5 mg, aprocitentan 25 mg or placebo; Part 2 single-blind (SB) aprocitentan 25 mg; Part 3: double-blind withdrawal (DB-WD) re-randomized to aprocitentan 25 mg or placebo.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantCare ProviderInvestigator
Drug: Aprocitentan 25 mg
Placebo in Part 3 (double-blind withdrawal)
Placebo Comparator
After 32-weeks in the single-blind, single-arm part (Part 2), participants will be re-randomized and receive placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
Drug: Placebo
ACT-132577
Aprocitentan 25 mg
Drug
Tablet, oral use
Aprocitentan 25 mg in Part 1 (double-blind)
Aprocitentan 25 mg in Part 2 (single-blind, single arm)
Aprocitentan 25 mg in Part 3 (double-blind withdrawal)
ACT-132577
Placebo
Drug
Matching placebo tablet
Placebo in Part 1 (double-blind)
Placebo in Part 3 (double-blind withdrawal)
Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40
Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure Measurement
Changes from baseline to Week 4 in mean trough SiDBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. A negative change indicates a decrease in SiDBP from baseline.
Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
Changes From Baseline to Week 4 of Double-blind Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring
ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (baseline and Week 4) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve and divided by the time span. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.
Pre-dose Day 1 (Part 1 double-blind randomized baseline) and Week 4 (End of double-blind randomized part 1)
Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure
Changes from double-blind withdrawal (Week 36) to Week 40 in mean trough SiDBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiDBP from baseline.
Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40
Changes From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring
ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (the double-blind withdrawal baseline [Week 36] and the week 40) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.
From Week 36 (Part 3 double-blind-withdrawal baseline) and Week 40
Inglewood
California
90301
United States
Clinical Trials Research
Lincoln
California
95648
United States
Academic Medical Research Institute Inc
Los Angeles
California
90022
United States
Amicis Research Center
Northridge
California
91324
United States
California Kidney Specialists
San Dimas
California
91773
United States
Bay Area Cardiology Associates, P.A.
Brandon
Florida
33511
United States
Century Clinical Research, Inc
Daytona Beach
Florida
32117
United States
Mayo Clinic Jacksonville
Jacksonville
Florida
32224
United States
Canvas Clinical Research, LLC
Lake Worth
Florida
33467
United States
East Coast Institute for Research
Saint Augustine
Florida
32086
United States
Premier Medical Associates
The Villages
Florida
32159
United States
SIU School of Medicine Center for Clinical Research
Springfield
Illinois
62702
United States
Midwest Institute for Clinical Research
Indianapolis
Indiana
46260
United States
Cardiovascular Research of Northwest Indiana, L.L.C.
Munster
Indiana
46231
United States
Reid Physician Associates
Richmond
Indiana
47374
United States
Grace Research, LLC
Bossier City
Louisiana
71111
United States
MedStar Health Research Institute
Hyattsville
Maryland
20782
United States
Clinical Research Consultants, LLC
Kansas City
Missouri
64111
United States
Hypertension and Nephrology Association PA
Eatontown
New Jersey
07724
United States
Renal Medicine Associates
Albuquerque
New Mexico
87109
United States
Albany Medical College
Albany
New York
12206
United States
Scott Research Inc
Laurelton
New York
11413
United States
Great Lakes Medical Research LLC
Westfield
New York
14787
United States
Metrolina Internal Medicine/Internal Medicine Research
Charlotte
North Carolina
28207
United States
East Carolina University
Greenville
North Carolina
27834
United States
Physician's East Endocrinology
Greenville
North Carolina
27834
United States
Carteret Medical Group
Morehead City
North Carolina
28557
United States
University Hospitals Cleveland Medical Center - Neurological Institute
Cleveland
Ohio
44106
United States
Willamette Valley Clinical Studies
Eugene
Oregon
97404
United States
TLM Medical Services LLC
Columbia
South Carolina
29204
United States
DeGarmo Institute of Medical Research
Greer
South Carolina
29650
United States
Stern Cardiovascular Foundation, Inc
Germantown
Tennessee
38138
United States
LifeDOC Research PLLC
Memphis
Tennessee
38119
United States
Amarillo Heart Clinical Research Institute, Inc.
Amarillo
Texas
79106
United States
LinQ Research, LLC
Pearland
Texas
77584
United States
Mercury Clinical Research
Webster
Texas
77598
United States
St. George Kidney Care LLC dba Southern Utah Kidney and Hypertension Center
St. George
Utah
84790
United States
Burke Internal Medicine & Research
Burke
Virginia
22015
United States
Manassas Clinical Research Center
Manassas
Virginia
20110
United States
Milwaukee Nephrologists, SC
Wauwatosa
Wisconsin
53226
United States
Renal Research
Gosford
New South Wales
2250
Australia
Westmead Hospital Department of Renal Medicine
Sydney
New South Wales
2145
Australia
Baker Heart and Diabetes Institute
Melbourne
Victoria
3004
Australia
Hypertension & Kidney Disease / Huma Neurotransmitter Laboratory
Melbourne
Victoria
3004
Australia
Curtin University, Faculty of Health Sciences, School of Public Health
Bentley
Western Australia
6102
Australia
Royal Perth Hospital Unit - The University of Western Australia
Perth
Western Australia
6000
Australia
Hospital Erasme - Cardiology department
Brussels
1070
Belgium
Clinique Universitaires de Saint Luc, Departement cardio-vasculaires intensives
Brussels
1200
Belgium
Universitair Ziekenhuis Gent Cardiologie
Ghent
9000
Belgium
Centre Hospitalier Universitaire du Sart-Tilman
Liège
4000
Belgium
Manna Research Inc (North Burlington)
Hamilton
Ontario
L8J 3W2
Canada
London Health Sciences Centre - Victoria Hospital
London
Ontario
N6A 5W9
Canada
Canadian Phase Onward Inc.
Toronto
Ontario
M3J 2C5
Canada
Stephen S. Chow Medicine Professional Corporation
Toronto
Ontario
M4C 5T2
Canada
Clinical Research Solutions Inc.
Waterloo
Ontario
N2J 3Z4
Canada
The First Affiliated Hospital of Baotou Medical College of Inner Mongolia
Baotou
014010
China
The Third Xiangya Hospital of Central South University
Changsha
410000
China
Guangdong General Hospital
Guangzhou
510080
China
Zhejiang Province People's Hospital
Hangzhou
310014
China
Hainan NO.3 Provincial people's Hospital
Sanya
572000
China
Ruijin Hospital Shanghai Jiaotong University School of Medicine
Shanghai
200000
China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an
710061
China
FN U Sv.Anny Brno, kardiologická klinika
Brno
656 91
Czechia
Všeobecní fakultní nemocnice Praha
Prague
128 08
Czechia
Thomayerova nemocnice
Prague
140 59
Czechia
Interni oddeleni, Nefrologie
Prague
16000
Czechia
Kardio Václavík s.r.o
Přerov
750 02
Czechia
University of Oulu, Medical Research Center
Oulu
90220
Finland
TAYS RDI center (Tampere University Hospital,Specialist Internal Medicine, Rare Diseases)
Tampere
33520
Finland
Turku University Central Hospital - Turun yliopistollinen keskussairaala Sisätautien klinikka
Turku
20520
Finland
CHU Grenoble - Alpes
Grenoble
38043
France
Hôpital de la Croix-Rousse - Rhône
Lyon
69317
France
Hôpital Européen Georges Pompidou- Centre d' Investigation Clinique
Paris
75015
France
Centre Hospitalier Intercommunal Toulon La Seyne sur Mer
Toulon
83100
France
Jewish Hospital Berlin
Berlin
13347
Germany
Universitätsklinikum Düsseldorf Klinik für Nephrologie
Herzzentrum Leipzig Universitätsklinik für Kardiologie
Leipzig
04289
Germany
Universitätsklinikum Nürnberg Süd
Nuremberg
90471
Germany
General Hospital of Athens, Ippokrateio
Athens
11527
Greece
General Hospital of Athens Georgios Gennimatas
Athens
15669
Greece
Asklepeion General Hospital
Athens
16673
Greece
General Hospital Konstantopouleio-Patision
Nea Ionia
14233
Greece
DRC Gyógyszervizsgáló Központ Kft.
Balatonfüred
8230
Hungary
Gottsegen György Országos Kardiológiai Intézet
Budapest
1096
Hungary
Debreceni Egyetem - Klinikai Központ
Debrecen
4032
Hungary
Markusovszky Egyetemi Oktatókórház
Szombathely
9700
Hungary
Haemek Medical Center
Afula
1834111
Israel
Barzilai Medical Center, Cardiovascular Institute
Ashkelon
7830604
Israel
Shaare Zedek Medical Center
Jerusalem
9103102
Israel
Galilee Medical Center
Nahariya
2210001
Israel
Sheba Medical Center
Tel Litwinsky
5265601
Israel
University Brescia Department Clinical and Experimental Science
Brescia
25121
Italy
Ospedale San Gerardo, Clinica Medica
Monza
20835
Italy
Azienda Ospedaliero Universitaria Pisana - Department Clinical and Experimental Medicine
Pisa
56126
Italy
Azienda Ospedaliera S. Andrea di Roma - Division of Cardiology and of Cardiothoracic and Vascular Science Department -
Roma
00189
Italy
SCU Medicina Interna e Centro Ipertensione arteriosa. Dipartimento di Scienze Mediche Università di Torino, Aou Citta' Salute E Scienza Torino
Torino
10126
Italy
JSC "InMedica"
Kaunas
LT-50177
Lithuania
Clinic of Cardiology and Rehabilitation
Klaipėda
LT-91131
Lithuania
Academic Medical Center Amsterdam
Amsterdam
1105 AZ
Netherlands
Zuyderland Medical Center
Geleen
6162 BG
Netherlands
Maastricht University Medical Center, Dept. of Medicine
Maastricht
6229 HX
Netherlands
Radboud University Medical Center
Nijmegen
6500 HB
Netherlands
Uniwersyteckie Centrum Kliniczne Centrum Kardiologii
Gdansk
80-214
Poland
Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mielęckiego Śląskiego Uniwersytetu Medycznego w Katowicach
Katowice
40-027
Poland
Diamond Clinic
Krakow
31-559
Poland
SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi
Lodz
92-213
Poland
KO-MED. CentraKliniczne Sp. Z o.o. Ośrodek Badań Klinicznych w Lublinie II
Lublin
20-362
Poland
ETG Lublin
Lublin
20-412
Poland
Etyka Ośrodek Badań Klinicznych
Olsztyn
10-117
Poland
KO-MED. Centra Kliniczne Sp. Z o.o. Ośrodek Badań Klinicznych w Puławach
Puławy
24-100
Poland
ETG Skierniewice
Skierniewice
96-100
Poland
Medycyna Kliniczna
Warsaw
00-874
Poland
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
Warsaw
02-097
Poland
ETG Warszawa
Warsaw
02-777
Poland
Klinika Wad Wrodzonych Serca Instytut Kardiologii im. Kardynala Wyszynskiego
Warsaw
04-628
Poland
Samodzielny Publiczny Szpital Wojewódzki im. Papieża Jana Pawła II w Zamościu
Zamość
22-400
Poland
ETG Zgierz
Zgierz
95-100
Poland
State Budgetary Healthcare Institution of Arkhangelsk Region "First City Clinical Hospital n.a. E.E. Volosevich"
Arkhangelsk
163001
Russia
Federal State Autonomous Institution of Higher Education "Kazan (Volga Region) Federal University"
Kazan'
420043
Russia
Federal State Budget Scientific Institution "Scientific Research Institute for Complex Issues of Cardiovascular Diseases"
Kemerovo
650002
Russia
Scientific Research Institute - Regional Clinical Hospital №1
Krasnodar
350086
Russia
National Medical Research Center for Preventive Medicine
Moscow
101990
Russia
State budget healthcare institution of Novosibirsk region "City clinical hospital #34"
Novosibirsk
630054
Russia
Federal State Budget Scientific Institution "Federal Research Center Institute of Cytology and Genetics of Siberian Department of Russian Academy of Sciences"
Novosibirsk
630089
Russia
Federal State Military Educational Institution of Higher Professional Education, Military Medical Academy named for S. M. Kirov of the Ministry of Defense of the Russian Federation
Saint Petersburg
194044
Russia
Federal State Budget Institution "National Medical Research Center n.a. V.A. Almazov" of the Ministry of healthcare of the Russian Federation
Saint Petersburg
197341
Russia
Federal State Budget Institution National Medical Research Center n.a. V.A. Almazov of the Ministry of Healthcare of the Russia
Saint Petersburg
197341
Russia
State Healthcare Institution "Regional Clinical Cardiology Dispensary"
Saratov
410028
Russia
Federal State Budget Educational Institution of Higher Education "Saratov State Medical University n.a. V.I. Razumovskiy" of the Ministry of Healthcare of the Russian Federation
Saratov
410054
Russia
State Budgetary Educational Institution of Higher Professional Education Smolensk State Medical Academy
Smolensk
214018
Russia
Federal State Budget Scientific Institution "Tomsk National Research Medical Center of the Russian Academy of Sciences"
Tomsk
634012
Russia
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Science
Tyumen
625026
Russia
Hospital del Mar
Barcelona
08003
Spain
Fundació Puigvert
Barcelona
08025
Spain
Hospital Vall d'Hebron de Barcelona
Barcelona
08035
Spain
Hospital Universitari de Bellvitge
Barcelona
08907
Spain
Hospital Virgen de las Nieves - Internal Medicine Department
Granada
18014
Spain
Hospital Clinico San Carlos - Istituto de Investigacion Sanitaria San Carlos (IdISSC)
Madrid
28040
Spain
Hospital Universitario La Paz
Madrid
28046
Spain
Hospital Virgen del Rocio Departamento de Medicina Interna
Seville
41013
Spain
Hospital Clínic Universitari de València
Valencia
46010
Spain
Hypertension Clinic, Internal Medicine, Hospital Clinico, University of Valencia, Valencia
Valencia
46010
Spain
State Institution "L.T. Malaya Therapy National Institute of the NAMS of Ukraine"
Kharkiv
61039
Ukraine
Municipal non-profit enterprise "Clinical Hospital # 8"of Kharkiv City Council
Kharkiv
61176
Ukraine
Kyiv City Clinical Hospital # 1
Kyiv
02091
Ukraine
Kyiv Municipal Clinical Emergency Hospital
Kyiv
02116
Ukraine
State Institution "National Scientific Center "M.D. Strazhesko Institute of Cardiology" of the National Academy of Medical Sciences of Ukraine"
Kyiv
03680
Ukraine
State Institution "D.F. Chebotarev Institute of Gerontology, National Academy of Medical Science of Ukraine"
Kyiv
04114
Ukraine
State Institution "Institute of Gerontology named after D.F. Chebotarev of National Academy of Medical Sciences of Ukraine"
Kyiv
04114
Ukraine
Volyn Regional Center for Cardiovascular Pathology, Rehabilitation Department
Lutsk
43024
Ukraine
Danylo Halytsky Lviv National Medical University
Lviv
79013
Ukraine
Communal Non-profit Enterprise "Vinnytsya regional Clinical Hospital named after. N.I. Pirogov Vinnytsia Regional Council"/ National Pirogov Memorial Medical University, Vinnytsya
Vinnytsia
21028
Ukraine
O.F. Herbachevsky Zhytomyr Regional Clinical Hospital, Cardiology department
Zhytomyr
10002
Ukraine
Aberdeen Royal Infirmary, Clinical Pharmacology Unit
Aberdeen
AB24 2ZN
United Kingdom
Clinical Research Centre The University of Edinburgh Centre for Cardiovascular Science
Edinburgh
EH4 2XU
United Kingdom
Queen Mary University of London
London
EC1M 6BQ
United Kingdom
Background
Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005 Feb 8;111(5):697-716. doi: 10.1161/01.CIR.0000154900.76284.F6.
Danaietash P, Verweij P, Wang JG, Dresser G, Kantola I, Lawrence MK, Narkiewicz K, Schlaich M, Bellet M; PRECISION investigators. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan. J Clin Hypertens (Greenwich). 2022 Jul;24(7):804-813. doi: 10.1111/jch.14517. Epub 2022 Jun 9.
Valdes PO, Pickard B, Orakwue C, Ferdinand K. Aprocitentan: An oral, once-daily antihypertensive therapy for resistant hypertension in adult patients. Heart Int. 2026 Feb 10;20(1):35-39. doi: 10.17925/HI.2026.20.1.1. eCollection 2026.
Flack JM, Schlaich MP, Weber MA, Sassi-Sayadi M, Narkiewicz K, Clozel M, Dreier RF, Andrawis NS, Danaietash P, Gabra N, Scott D, Wang JG, Ferdinand KC. Aprocitentan for Blood Pressure Reduction in Black Patients. Hypertension. 2025 Apr;82(4):601-610. doi: 10.1161/HYPERTENSIONAHA.124.24142. Epub 2025 Jan 22.
Schlaich MP, Bellet M, Weber MA, Danaietash P, Bakris GL, Flack JM, Dreier RF, Sassi-Sayadi M, Haskell LP, Narkiewicz K, Wang JG; PRECISION investigators. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial. Lancet. 2022 Dec 3;400(10367):1927-1937. doi: 10.1016/S0140-6736(22)02034-7. Epub 2022 Nov 7.
Participants were randomized and received aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
FG002
Placebo in Part 1 (Double-blind)
Participants were randomized and received placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
FG003
Aprocitentan 25 mg in Part 2 (Single-blind)
Participants that completed the double-blind part received aprocitentan 25 mg, orally, once daily in the morning for 32 weeks.
FG004
Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal)
After the 32-week single-blind, single-arm aprocitentan 25 mg (Part 2), participants were re-randomized and received aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
FG005
Placebo in Part 3 (Double-blind Withdrawal)
After the 32-week single-blind, single-arm aprocitentan 25 mg (Part 2), participants were re-randomized and received placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
FG000243 subjects
FG001243 subjects
FG002244 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Safety Set
Two participants randomized to placebo received at least one dose of aprocitentan 25 mg during double-blind part 1.
FG000243 subjects
FG001245 subjects
FG002242 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG000232 subjects
FG001234 subjects
FG002238 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG00011 subjects
FG0019 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0006 subjects
FG0015 subjects
FG0022 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Withdrawal by Subject
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Other reasons
FG0003 subjects
FG0012 subjects
FG0023 subjects
FG0030 subjects
FG004
Part 2 Single-Blind
Type
Comment
Milestone Data
STARTED
FG0000 subjectsThe 232 participants that completed 12.5 mg aprocitentan study treatment in part 1 entered the single-blind 25 mg aprocitentan arm in part 2.
FG0010 subjectsThe 236 participants that completed 25 mg aprocitentan study treatment in part 1 entered the single-blind 25 mg aprocitentan arm in part 2.
FG0020 subjectsThe 236 participants that completed placebo study treatment in part 1 entered the single-blind 25 mg aprocitentan arm in part 2.
FG003704 subjectsTotal number of participants that completed the double-blind part 1 who entered the single-blind, single-arm part 2.
FG0040 subjects
FG0050 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003613 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00391 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 3 Double-Blind Withdrawal
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004307 subjects
FG005307 subjects
Safety Set
613 participants started study treatment in Part 3. Four participants re-randomised to placebo received at least one dose of aprocitentan 25 mg during part 3.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Aprocitentan 12.5 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
BG001
Aprocitentan 25 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
BG002
Placebo in Part 1 (Double-blind)
Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000243
BG001243
BG002244
BG003730
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00061.2± 10.3
BG00161.7± 10.4
BG00262.2± 11.2
BG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Female
BG00099
BG00198
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00028
BG00122
BG002
Race (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Australia
Title
Measurements
BG0008
BG0018
BG002
Body Mass Index at Screening Visit
Mean
Standard Deviation
kg/m^2
Title
Denominators
Categories
Title
Measurements
BG00033.6± 6.2
BG00134.3± 6.8
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Automated Office Blood Pressure Measurement
Changes from baseline to Week 4 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.
The Full Analysis Set (FAS) includes all participants who were randomized and had a baseline sitting systolic blood pressure, measured by automated office blood pressure measurement. Baseline was defined as the last measurement before randomization.
Posted
Least Squares Mean
97.5% Confidence Interval
mmHg
Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
ID
Title
Description
OG000
Aprocitentan 12.5 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
OG001
Aprocitentan 25 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
OG002
Placebo in Part 1 (Double-blind)
Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Units
Counts
Participants
OG000243
OG001243
OG002244
Title
Denominators
Categories
Title
Measurements
OG000-15.26(-17.36 to -13.17)
OG001-15.20(-17.27 to -13.13)
OG002-11.47(-13.57 to -9.38)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Mixed Models Analysis
0.0042
Mixed effects model for Repeated Measures: Change from baseline in SiSBP = baseline SiSBP + treatment + visit + treatment x visit + baseline x visit.
LS Mean difference to placebo
-3.79
2-Sided
97.5
-6.76
-0.82
Superiority
OG001
OG002
Secondary
Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Unattended Automated Office Blood Pressure Measurement
Changes from double-blind withdrawal baseline (Week 36) to Week 40 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.
The modified FAS (mFAS) includes all participants from the FAS who were re-randomized in the double-blind-withdrawal part (DB-WD) of the study and who have a DB-WD baseline sitting systolic blood pressure, measured by automatic office blood pressure measurement device at trough. Baseline was defined as the last measurement before re-randomization.
Posted
Least Squares Mean
95% Confidence Interval
mmHg
Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40
ID
Title
Description
OG000
Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants were re-randomized to aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
Secondary
Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure Measurement
Changes from baseline to Week 4 in mean trough SiDBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. A negative change indicates a decrease in SiDBP from baseline.
The Full Analysis Set (FAS) includes all participants who were randomized and had a baseline sitting systolic blood pressure, measured by automated office blood pressure measurement. Baseline was defined as the last measurement before randomization.
Posted
Least Squares Mean
95% Confidence Interval
mmHg
Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
ID
Title
Description
OG000
Aprocitentan 12.5 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
Secondary
Changes From Baseline to Week 4 of Double-blind Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring
ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (baseline and Week 4) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve and divided by the time span. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.
The ambulatory blood pressure monitoring full analysis set (aFAS) includes all participants from the FAS who have a baseline 24-hour mean systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring with a total duration of at least 21 hours and at least 70% valid readings.
Posted
Least Squares Mean
95% Confidence Interval
mmHg
Pre-dose Day 1 (Part 1 double-blind randomized baseline) and Week 4 (End of double-blind randomized part 1)
ID
Title
Description
OG000
Aprocitentan 12.5 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
Secondary
Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure
Changes from double-blind withdrawal (Week 36) to Week 40 in mean trough SiDBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiDBP from baseline.
The modified FAS (mFAS) includes all participants in the FAS who were re-randomized in the double-blind-withdraw part of the study and who had a week 36 sitting systolic blood pressure, measured by automated office blood pressure measurement. Baseline was defined as the last measurement before re-randomization into part 3 of the double-blind withdrawal part of the study.
Posted
Least Squares Mean
95% Confidence Interval
mmHg
Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40
ID
Title
Description
OG000
Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal)
Secondary
Changes From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring
ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (the double-blind withdrawal baseline [Week 36] and the week 40) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.
The modified ambulatory blood pressure monitoring full analysis set (maFAS) includes all participants from the modified Full Analysis Set (mFAS) who had a double-blind withdrawal (DB-WD) baseline 24-hour mean systolic and diastolic blood pressure, measured by ambulatory blood Pressure monitoring (ABPM) with a total duration of at least 21 hours and at least 70% valid readings.
Posted
Least Squares Mean
95% Confidence Interval
mmHg
From Week 36 (Part 3 double-blind-withdrawal baseline) and Week 40
ID
Title
Description
OG000
Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants were re-randomized to aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
Time Frame
Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks.
Description
Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Aprocitentan 12.5 mg in Part 1 (Double-blind)
Participants received aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.
1
243
8
243
16
243
EG001
Aprocitentan 25 mg in Part 1 (Double-blind)
Participants received aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
0
245
8
245
34
245
EG002
Placebo in Part 1 (Double-blind)
Participants received placebo, orally, once daily in the morning for 4 weeks.
0
242
3
242
5
242
EG003
Aprocitentan 25 mg in Part 2 (Single-blind)
All participants received aprocitentan 25 mg, orally, once daily in the morning for 32 weeks.
9
704
82
704
95
704
EG004
Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants received aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
1
310
18
310
6
310
EG005
Placebo in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants received placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
0
303
9
303
4
303
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG0031 events1 affected704 at risk
EG0040 events0 affected310 at risk
EG0050 events0 affected303 at risk
Acute left ventricular failure
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Angina unstable
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Atrioventricular block
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Atrioventricular block second degree
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cardiac failure
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cardiac failure acute
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cardiac failure chronic
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cardiogenic shock
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Coronary artery dissection
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Left ventricular dysfunction
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Meniere's disease
Ear and labyrinth disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Vestibular ataxia
Ear and labyrinth disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Pancreatitis chronic
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Rectal fissure
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Umbilical hernia, obstructive
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Chest pain
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Death
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Multiple organ dysfunction syndrome
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Oedema peripheral
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Pyrexia
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Sudden cardiac death
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Abscess jaw
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
COVID-19
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0002 events2 affected243 at risk
EG0010 events0 affected245 at risk
EG0021 events1 affected242 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0012 events2 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cholecystitis infective
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Diabetic gangrene
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Erysipelas
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Peritonsillar abscess
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0021 events1 affected242 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Pneumonia bacterial
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Pyelonephritis acute
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0021 events1 affected242 at risk
EG003
Sepsis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0021 events1 affected242 at risk
EG003
Ureteritis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Wound infection
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Chest injury
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Procedural intestinal perforation
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Subdural haemorrhage
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Traumatic intracranial haemorrhage
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Blood pressure increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Osteochondrosis
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Rotator cuff syndrome
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Adenocarcinoma of colon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Invasive breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Lung neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Mantle cell lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Metastatic neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Renal cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Renal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cerebral infarction
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Facial paresis
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0021 events1 affected242 at risk
EG003
Seizure
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Syncope
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Calculus urinary
Renal and urinary disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Nephropathy toxic
Renal and urinary disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Ureteric stenosis
Renal and urinary disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Endometrial hyperplasia
Reproductive system and breast disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Uterine polyp
Reproductive system and breast disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0011 events1 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Angioedema
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Coronary artery bypass
Surgical and medical procedures
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hip arthroplasty
Surgical and medical procedures
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Peripheral artery bypass
Surgical and medical procedures
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Toe amputation
Surgical and medical procedures
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Aortic stenosis
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0001 events1 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Distributive shock
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hypertension
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hypertensive crisis
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hypertensive urgency
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Hypotension
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Intermittent claudication
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Peripheral artery stenosis
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0000 events0 affected243 at risk
EG0010 events0 affected245 at risk
EG0020 events0 affected242 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Oedema peripheral
General disorders
MedDRA (24.1)
Systematic Assessment
EG00016 events16 affected243 at risk
EG00134 events34 affected245 at risk
EG0025 events5 affected242 at risk
EG003102 events95 affected704 at risk
EG0047 events6 affected310 at risk
EG0054 events4 affected303 at risk
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Any study-related publication written independently by investigators must be submitted to the sponsor for review at least 30 days prior to submission for publication or presentation at a congress. Upon review, the sponsor may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights. Neither the institution nor the investigator should permit publication during such a review period.
Re-randomized in part 3, however no drug dispensed
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
61.7
± 10.6
99
BG003296
Male
BG000144
BG001145
BG002145
BG003434
23
BG00373
Not Hispanic or Latino
BG000213
BG001219
BG002218
BG003650
Unknown or Not Reported
BG0002
BG0012
BG0023
BG0037
0
BG0030
Asian
BG00011
BG00114
BG00213
BG00338
Native Hawaiian or Other Pacific Islander
BG0001
BG0010
BG0020
BG0031
Black or African American
BG00028
BG00128
BG00226
BG00382
White
BG000203
BG001200
BG002202
BG003605
More than one race
BG0000
BG0010
BG0020
BG0030
Unknown or Not Reported
BG0000
BG0011
BG0023
BG0034
7
BG00323
Belgium
Title
Measurements
BG0001
BG0013
BG0024
BG0038
Canada
Title
Measurements
BG0008
BG0017
BG0026
BG00321
China
Title
Measurements
BG0006
BG00111
BG00210
BG00327
Czechia
Title
Measurements
BG00010
BG0013
BG00215
BG00328
Finland
Title
Measurements
BG0009
BG0015
BG0022
BG00316
France
Title
Measurements
BG0000
BG0014
BG0023
BG0037
Germany
Title
Measurements
BG0003
BG0016
BG0029
BG00318
Greece
Title
Measurements
BG0005
BG0011
BG0022
BG0038
Hungary
Title
Measurements
BG0001
BG0014
BG0021
BG0036
Israel
Title
Measurements
BG0005
BG0012
BG0023
BG00310
Italy
Title
Measurements
BG0003
BG0012
BG0020
BG0035
Lithuania
Title
Measurements
BG0002
BG0014
BG0024
BG00310
Netherlands
Title
Measurements
BG0002
BG0013
BG0023
BG0038
Poland
Title
Measurements
BG00015
BG00116
BG00220
BG00351
Russia
Title
Measurements
BG00061
BG00156
BG00249
BG003166
Spain
Title
Measurements
BG0004
BG0018
BG0026
BG00318
Ukraine
Title
Measurements
BG00030
BG00126
BG00230
BG00386
United Kingdom
Title
Measurements
BG0002
BG0010
BG0021
BG0033
United States
Title
Measurements
BG00068
BG00174
BG00269
BG003211
33.3
± 5.6
BG00333.7± 6.2
Mixed Models Analysis
0.0046
Mixed effects model for Repeated Measures: Change from baseline in SiSBP = baseline SiSBP + treatment + visit + treatment x visit + baseline x visit.
LS Mean difference to placebo
-3.73
2-Sided
97.5
-6.67
-0.78
Superiority
OG001
Placebo in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants were re-randomized to placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
Units
Counts
Participants
OG000307
OG001307
Title
Denominators
Categories
Title
Measurements
OG000-1.47(-2.97 to 0.04)
OG0014.36(2.87 to 5.85)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
<0.0001
Mixed effects model for Repeated Measures: Change from DB-WD baseline in SiSBP = DB-WD baseline SiSBP + stratum (randomized treatment in DB part) + treatment + visit + treatment x visit + DB-WD baseline x visit.
LS mean difference to placebo.
-5.82
2-Sided
95
-7.94
-3.71
Superiority
OG001
Aprocitentan 25 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
OG002
Placebo in Part 1 (Double-blind)
Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Units
Counts
Participants
OG000243
OG001243
OG002244
Title
Denominators
Categories
Title
Measurements
OG000-10.43(-11.58 to -9.27)
OG001-10.95(-12.09 to -9.82)
OG002-6.48(-7.63 to -5.33)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Mixed Models Analysis
<0.0001
Mixed effects model for Repeated Measures: Change from baseline in SiDBP = baseline SiDBP + treatment + visit + treatment x visit + baseline x visit.
LS Mean difference to placebo
-3.94
2-Sided
95
-5.57
-2.31
Other
OG001
OG002
Mixed Models Analysis
<0.0001
Mixed effects model for Repeated Measures: Change from baseline in SiDBP = baseline SiDBP + treatment + visit + treatment x visit + baseline x visit.
LS Mean difference to placebo
-4.47
2-Sided
95
-6.09
-2.85
Other
OG001
Aprocitentan 25 mg in Part 1 (Double-blind)
Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.
OG002
Placebo in Part 1 (Double-blind)
Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Units
Counts
Participants
OG000206
OG001207
OG002220
Title
Denominators
Categories
24-hour mean systolic blood pressure
Title
Measurements
OG000-6.73(-8.20 to -5.26)
OG001-8.44(-9.88 to -7.00)
OG002-2.55(-4.00 to -1.10)
24-hour mean diastolic blood pressure
Title
Measurements
OG000-6.25(-7.20 to -5.29)
OG001-7.74(-8.67 to -6.80)
OG002-1.92(-2.87 to -0.98)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
24-hour mean systolic (SBP)
ANCOVA
<0.0001
LS Mean difference to placebo
-4.18
2-Sided
95
-6.25
-2.12
Other
OG001
OG002
24-hour mean systolic (SBP)
ANCOVA
<0.0001
LS Mean difference to placebo
-5.90
2-Sided
95
-7.94
-3.85
Other
OG000
OG002
24-hour mean diastolic (DBP)
ANCOVA
<0.0001
LS Mean difference to placebo
-4.32
2-Sided
95
-5.66
-2.98
Other
OG001
OG002
24-hour mean diastolic (DBP)
ANCOVA
<0.0001
LS Mean
-5.81
2-Sided
95
-7.14
-4.49
Other
After 32-weeks in the single-blind, single-arm part, participants were re-randomized to aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.
OG001
Placebo in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants were re-randomized to placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
Units
Counts
Participants
OG000307
OG001307
Title
Denominators
Categories
Title
Measurements
OG000-0.52(-1.54 to 0.50)
OG0014.67(3.66 to 5.68)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
<0.0001
Mixed effects model for Repeated Measures: Change from DB-WD baseline in SiDBP = Double-blind withdrawal baseline SiDBP + stratum (randomized treatment in DB part) + treatment + visit + treatment x visit + Double-blind withdrawal baseline x visit.
LS Mean difference to placebo
-5.19
2-Sided
95
-6.62
-3.76
Other
OG001
Placebo in Part 3 (Double-blind Withdrawal)
After 32-weeks in the single-blind, single-arm part, participants were re-randomized to placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.