Dose-finding Study With ACT-132577 (Aprocitentan) in Part... | NCT02603809 | Trialant
NCT02603809
Sponsor
Idorsia Pharmaceuticals Ltd.
Status
Completed
Last Update Posted
Nov 23, 2022Actual
Enrollment
1,659Actual
Phase
Phase 2
Conditions
Essential Hypertension
Interventions
Aprocitentan 5 mg
Aprocitentan 10 mg
Aprocitentan 25 mg
Aprocitentan 50 mg
Lisinopril 20 mg
Placebo
Countries
United States
Canada
Israel
Puerto Rico
Protocol Section
Identification Module
NCT ID
NCT02603809
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
AC-080A201
Secondary IDs
Not provided
Brief Title
Dose-finding Study With ACT-132577 (Aprocitentan) in Participants With Essential Hypertension
Official Title
A Multi-center, Double-blind, Double-dummy, Randomized, Placebo- and Active-reference, Parallel Group, Phase 2, Dose-finding Study With ACT-132577 in Subjects With Essential Hypertension (Grade 1 and 2).
Acronym
Not provided
Organization
Idorsia Pharmaceuticals Ltd.INDUSTRY
Status Module
Record Verification Date
Nov 2022
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
Dec 14, 2015Actual
Primary Completion Date
Feb 28, 2017Actual
Completion Date
Apr 7, 2017Actual
First Submitted Date
Nov 9, 2015
First Submission Date that Met QC Criteria
Nov 11, 2015
First Posted Date
Nov 13, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 27, 2020
Results First Submitted that Met QC Criteria
Mar 31, 2020
Results First Posted Date
Apr 13, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 26, 2018
Certification/Extension First Submitted that Passed QC Review
Mar 28, 2018
Certification/Extension First Posted Date
Mar 29, 2018Actual
Last Update Submitted Date
Nov 22, 2022
Last Update Posted Date
Nov 23, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Idorsia Pharmaceuticals Ltd.INDUSTRY
Collaborators
Not provided
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 main objective will be to evaluate the dose-response of ACT-132577 (aprocitentan) on diastolic blood pressure (DBP) in participants with grade 1 or 2 essential hypertension.
Secondary objectives will be to evaluate the dose-response of ACT-132577 on: systolic blood pressure (SBP); control and response rate of blood pressure; 24-hour ambulatory blood pressure monitoring (ABPM) and to evaluate the safety and tolerability of a once daily oral regimen of 4 doses of ACT-132577.
Detailed Description
Participation in the study is planned to last up to 18 weeks. A single-blind placebo run-in period of 4 to 6 weeks after which participants will be randomized into a double-blind treatment period of 8 weeks and a washout and follow-up period ending with an end-of-study visit approximately 12 weeks after randomization.
Conditions Module
Conditions
Essential 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 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
1,659Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received placebo orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
Drug: Placebo
Aprocitentan 5 mg
Experimental
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
Drug: Aprocitentan 5 mg
Aprocitentan 10 mg
Experimental
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan 10 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
Drug: Aprocitentan 10 mg
Aprocitentan 25 mg
Experimental
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan 25 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Aprocitentan 5 mg
Drug
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
Aprocitentan 5 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
The absolute change in mean trough sitting diastolic blood pressure (SiDBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the diastolic blood pressure from the start of treatment.
Baseline (Day 1) and end of double-blind treatment (Day 56)
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline to End of Double-blind Treatment in Sitting Systolic Blood Pressure at Trough
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
The absolute change in mean trough sitting systolic blood pressure (SiSBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the systolic blood pressure from the start of treatment.
Other Outcomes
Measure
Description
Time Frame
Supportive Analysis of Primary Endpoint: Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
The absolute change in mean trough sitting diastolic blood pressure (SiDBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the diastolic blood pressure from the start of treatment.
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Signed informed consent prior to any study-mandated procedure
No contra-indication to stop (according to label) anti-hypertensive treatment(s) at screening
Mild-to-moderate essential hypertension with or without ongoing anti-hypertensive treatment(s):
-- Mean (of 5 measurements) sitting diastolic blood pressure (SiDBP) ≥ 90 to < 110 mmHg measured by office blood pressure measurements (OBPM).
Women of childbearing potential must have a negative pregnancy test and use of reliable methods of contraception
Exclusion Criteria:
Severe hypertension (grade 3): mean sitting systolic/diastolic BP (SiSBP/SiDBP; measured by OBPM) ≥ 180/110 mmHg, respectively.
Secondary hypertension
Known hypertensive retinopathy greater than Keith-Wagener Grade 2
Myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft within 12 months prior to randomization
Unstable angina within 6 months prior to randomization
Heart failure New York Heart Association class III and IV
Valvular defects (such as severe aortic or mitral valve disease) and/or hemodynamically relevant rhythm disturbances
Clinical evidence of cerebrovascular insufficiency or a cerebrovascular accident within 6 months prior to randomization.
Subjects working night shifts
Body mass index < 20 kg/m2 or > 40 kg/m2
Treatment with any medication which may affect BP (e.g., treatment of psychiatric diseases, ophthalmic preparations)
Treatment with strong cytochrome P450 3A4 (CYP3A4) isoenzyme inhibitors or inducers
Treatment with guanethidine and/or mineralocorticoid receptor antagonists within 1 month prior to Screening (Visit 1)
Treatment with another investigational treatment within 1 month prior to Screening (Visit 1)
Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Verweij P, Danaietash P, Flamion B, Menard J, Bellet M. Randomized Dose-Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension. Hypertension. 2020 Apr;75(4):956-965. doi: 10.1161/HYPERTENSIONAHA.119.14504. Epub 2020 Feb 17.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Of the 996 participants enrolled into the run-in period, a total 992 participants received at least one dose of the single-blind placebo. Of these 992 participants 502 were considered run-in failures (390 failing to meet randomization criteria, 57 withdrew consent and 55 left for other reasons) and 490 participants were randomized into the study.
Recruitment Details
The study was conducted at 99 sites in 3 countries. Of the 1659 participants that signed the informed consent 996 entered the run-in period (i.e. 663 participants were screening failures: 651 failed to meet the eligibility criteria to enter the run-in period, 6 withdrew and 6 did not enter the run-in period for other reasons).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
After a 4 to 6-week single-blind placebo run-in period, participants received placebo orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received aprocitentan 50 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
Drug: Aprocitentan 50 mg
Lisinopril 20 mg
Active Comparator
After a 4 to 6-week single-blind placebo run-in period, participants will be randomized to received lisinopril 20 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
Drug: Lisinopril 20 mg
ACT-132577
Aprocitentan 10 mg
Drug
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
Aprocitentan 10 mg
ACT-132577
Aprocitentan 25 mg
Drug
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
Aprocitentan 25 mg
ACT-132577
Aprocitentan 50 mg
Drug
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
Aprocitentan 50 mg
ACT-132577
Lisinopril 20 mg
Drug
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan
Lisinopril 20 mg
Placebo
Drug
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
Placebo
Baseline (Day 1) and end of double-blind treatment (Day 56)
Control Rates at the End of the Double-blind Treatment Period Based on Trough Sitting Diastolic and Systolic Blood Pressure
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis. The Canadian Hypertension Education Program (CHEP) issued guidelines proposing cut-offs of 85 mmHg for diastolic blood pressure and 135 mmHg for systolic blood pressure specifically focusing on measurement by automated office blood pressure measurement. The number of participants at the end of the 8-week treatment period that had values below the protocol and CHEP cut-off values are reported.
The initial protocol control rates at Week 8 (Day 56) on trough SiDBP are also reported and were defined as a SiDBP of less than 90 mmHg and a SiSBP of less than 140 mmHg.
End of double-blind treatment (Day 56)
Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Diastolic Blood Pressure
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
A participant was a responder if the reduction from baseline in mean trough sitting diastolic blood pressure (SiDBP) was 10 mmHg or greater-than 10 mmHg.
Baseline (Day 1) and end of double-blind treatment (Day 56)
Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Systolic Blood Pressure
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
A participant was a responder if the reduction from baseline in mean trough sitting systolic blood pressure (SiSBP) was 20 mmHg or greater-than 20 mmHg.
Baseline (Day 1) and end of double-blind treatment (Day 56)
Change From Baseline to End of Double-blind Treatment in 24-hour Diastolic and Systolic Ambulatory Blood Pressure Monitoring (ABPM)
Diastolic and systolic ambulatory blood pressure monitoring was performed over a 24-hour period with the ABPM device (Mobil-o-Graph) set to record diastolic and systolic blood pressure at a pre-defined time. Over a 24-hour period 3 measurements per hour during the day and 2 per hour during the night were made. The blood pressure measurements were derived from the area under the diastolic and systolic blood pressure curves and divided by the time span and averaged.
For ambulatory blood pressure monitoring the baseline was the period from the time of last run-in placebo intake up to the time of the first double-blind treatment intake.
Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)
Ratio of Group Mean at Trough to Group Mean at Peak for Diastolic Blood Pressure Based on Ambulatory Blood Pressure Monitoring (ABPM)
Ratio of group mean at trough to group mean at peak was calculated from the diastolic ambulatory blood pressure monitoring performed over a 24-hour period with the ABPM device. The trough (the smallest blood pressure reduction) and the peak (the highest blood pressure reduction) ratio show the extent of blood pressure lowering throughout the 24-hour dosing interval in the group.
The group mean trough (at 20-24 hours) to group mean (at 2-6 hours) peak of diastolic blood pressure were examined to evaluate the extent to which once-daily dosing criteria were met (trough-to-peak values greater than 0.5).
The ratio is positive if there was a decrease in diastolic blood pressure at both the trough and peak times at the end of treatment (Day 55 to Day 56) when compared to baseline (Day -1 to Day 1).
For ambulatory blood pressure monitoring the baseline was the period from the time of last run-in placebo intake up to the time of the first double-blind treatment intake.
Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)
Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)
Chandler
Arizona
85224
United States
Warner Family Practice / Radiant Research Inc
Chandler
Arizona
85224
United States
Phoenix Medical Research Institute LLC
Peoria
Arizona
85381
United States
Advanced Arizona Clinical Research
Tucson
Arizona
85704
United States
Noble Clinical Research LLC
Tucson
Arizona
85704
United States
Desert Sun Clinical Research LLc
Tucson
Arizona
85710
United States
Advanced Research Center Inc
Anaheim
California
92805
United States
Med Center
Carmichael
California
95608
United States
John Muir Physician Network Clinical Research Center
Concord
California
94520
United States
Clinical Trials Research
Lincoln
California
95648
United States
Long Beach Center for Clinical Research
Long Beach
California
90807
United States
Entertainment Medical Group Inc
Los Angeles
California
90036
United States
Artemis institute for Clinical Research
San Diego
California
92103
United States
Memorial Research Medical Clinic / Orange County Research Center
Tustin
California
92780
United States
Empire Clinical Research
Upland
California
91786
United States
Clinical Research Consulting LLC
Milford
Connecticut
06460
United States
Chase Medical Research LLC
Waterbury
Connecticut
06708
United States
Alfieri Cardiology
Wilmington
Delaware
19803
United States
ACRC - Cardiology
Atlantis
Florida
33462
United States
Innovative Research of West Florida INC
Clearwater
Florida
33756
United States
Avail Clinical Research LLC
DeLand
Florida
32720
United States
Alan Graff, MD, PA
Fort Lauderdale
Florida
33308
United States
Gulfcoast Clinical Research Center
Fort Myers
Florida
33912
United States
AGA Clinical Trials
Hialeah
Florida
33012
United States
Canvas Clinical Research, LLC
Lake Worth
Florida
33467
United States
LCC Medical Research Institute
Miami
Florida
33126
United States
Allied Biomedical Research Institute, INC
Miami
Florida
33155
United States
Southeast Regional Research Group
Savannah
Georgia
31401
United States
Community Clin Res CTR
Anderson
Indiana
46011
United States
Midwest Institute for Clinical Research
Indianapolis
Indiana
46260
United States
Heartland Research Associated LLC
Newton
Kansas
67114
United States
Heartland Research Associates LLC
Wichita
Kansas
67205
United States
Heartland Research Associates LLC
Wichita
Kansas
67207
United States
Avant Research Associates, LLC
Crowley
Louisiana
70526
United States
Best Clinical Trials LLC
New Orleans
Louisiana
70115
United States
New Orleans Center for Clinical Research - Nola
New Orleans
Louisiana
70119
United States
Clinsite LLC
Ann Arbor
Michigan
48106
United States
Primecare Research Associates, LLC
Florissant
Missouri
63031
United States
Clinical Research Advantage, Inc. / Diagnostic Center Of Medicine - Durango
Las Vegas
Nevada
89117
United States
Premier Research
Trenton
New Jersey
08611
United States
Rochester Clinical Research Inc.
Rochester
New York
14609
United States
Metrolina Internal Medicine/Internal Medicine Research
Charlotte
North Carolina
28204
United States
Pharmquest LLC
Greensboro
North Carolina
27408
United States
Peters Medical Research
High Point
North Carolina
27262
United States
Wake Research Associates
Raleigh
North Carolina
27604-1547
United States
Lillestol Research LLC
Fargo
North Dakota
58103
United States
Sterling Research Group Ltd.
Cincinnati
Ohio
45219
United States
Aventiv Research Inc.
Columbus
Ohio
43213
United States
Dayton Clinical Research
Dayton
Ohio
45406
United States
Aventiv Research Inc.
Dublin
Ohio
43016
United States
Oklahoma City Clinic - Edmond / Radiant Research Inc
Edmond
Oklahoma
73034
United States
Clinical Research Advantage, Inc. / Oklahoma City Clinic - Midwest City
Midwest City
Oklahoma
73110
United States
Willamette Valley Clinical Studies
Eugene
Oregon
97404
United States
Detweiler Family Medicine and Associates PC
Lansdale
Pennsylvania
19446
United States
Suburban Research Center
Media
Pennsylvania
19063
United States
Degarmo Institute of Medical Research
Greer
South Carolina
29651
United States
Volunteer Research Group
Knoxville
Tennessee
37920
United States
Tekton Research Inc
Austin
Texas
78745
United States
Texas Diabetes & Endocrinology
Austin
Texas
78749
United States
Trinity Hypertension & Metabolic Research Institute
Carrollton
Texas
75006
United States
Family Medicine Associates of Texas - ACRC Trials
Carrollton
Texas
75010
United States
Coastal Bend Clinical Research
Corpus Christi
Texas
78413
United States
TR - Global Medical Research
DeSoto
Texas
75115
United States
Ventavia Research Group, LLC
Fort Worth
Texas
76104
United States
Clinical Investigations of Texas
Plano
Texas
75075
United States
Avant Research Associates LLC
Port Arthur
Texas
77640
United States
Texas Diabetes & Endocrinology
Round Rock
Texas
78681
United States
Radiant Research Inc
San Antonio
Texas
78229
United States
Bandera Family Health Care
San Antonio
Texas
78249
United States
Wasatch Clinical Research LLC
Salt Lake City
Utah
84107
United States
Health Research of Hampton Roads
Newport News
Virginia
23606
United States
National Clinical Research Inc
Richmond
Virginia
23294
United States
Northwest Clinical Research Center
Bellevue
Washington
98007
United States
Manna Research - Vancouver
Vancouver
British Columbia
V6J 1S3
Canada
Canadian Phase Onwards Inc
Toronto
Ontario
M3J 2C5
Canada
Manna Research - Toronto
Toronto
Ontario
M9W 4L6
Canada
Manna Research - Levis
Lévis
Quebec
G6W 0M6
Canada
Diex Recherche Montreal Inc
Montreal
Quebec
H2Y 1S1
Canada
Manna Research - Pointe Claire
Pointe-Claire
Quebec
H9R 4S3
Canada
Diex Reserach Sherbrooke Inc
Sherbrooke
Quebec
J1H 1Z1
Canada
Cardiology Department Barzilai
Ashkelon
78278
Israel
Soroka University Hospital - Hypertension Unit
Beersheba
84101
Israel
The Hyper Unit, Edith Wolfson Medical Center
Holon
58100
Israel
Hypertension Treatment Center, Internal Dep, Hadassah
Jerusalem
91240
Israel
Hypertension And Nephrology Department, Meir Medical Center
Kefar Sava
44261
Israel
Clinical Research Unit Kaplan Medical Center
Rehovot
76100
Israel
Internal Med Department A, Ziv Medical Center
Safed
13100
Israel
Advanced Medical Concepts, PSC
Cidra
00739
Puerto Rico
Research & Cardiovascular Corp.
Ponce
00717
Puerto Rico
Aprocitentan 5 mg
After a 4 to 6-week single-blind placebo run-in period, participants received 5 mg aprocitentan orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
FG002
Aprocitentan 10 mg
After a 4 to 6-week single-blind placebo run-in period, participants received aprocitentan 10 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
FG003
Aprocitentan 25 mg
After a 4 to 6-week single-blind placebo run-in period, participants received aprocitentan 25 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
FG004
Aprocitentan 50 mg
After a 4 to 6-week single-blind placebo run-in period, participants received aprocitentan 50 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
FG005
Lisinopril 20 mg
After a 4 to 6-week single-blind placebo run-in period, participants received lisinopril 20 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
FG00082 subjects
FG00182 subjects
FG00282 subjects
FG00382 subjects
FG00481 subjects
FG00581 subjects
Per-protocol Set
FG00067 subjects
FG00168 subjects
FG00271 subjects
FG00367 subjects
FG00468 subjects
FG00569 subjects
Modified Per-Protocol Set
FG00066 subjectsOne participant had out of analysis window blood pressure measurements.
FG00168 subjects
FG00271 subjects
FG00367 subjects
FG00468 subjects
FG00569 subjects
Completed Study
Participants that completed the 30-day follow-up telephone call / visit (i.e., End-of-Study).
FG00075 subjects
FG00179 subjects
FG00279 subjects
FG00376 subjects
FG00478 subjects
FG00575 subjects
COMPLETED
Participants that completed the 8-week treatment period.
FG00070 subjects
FG00174 subjects
FG00275 subjects
FG00370 subjects
FG00470 subjects
FG00571 subjects
NOT COMPLETED
FG00012 subjects
FG0018 subjects
FG0027 subjects
FG00312 subjects
FG00411 subjects
FG00510 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0004 subjects
FG0011 subjects
FG0022 subjects
FG0033 subjects
FG0043 subjects
FG0054 subjects
Lost to Follow-up
FG0002 subjects
FG0013 subjects
FG0021 subjects
FG0034 subjects
FG004
Pre-specified discontinuation criteria
FG0003 subjects
FG0013 subjects
FG0022 subjects
FG0032 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Adverse Event
FG0003 subjects
FG0010 subjects
FG0022 subjects
FG0032 subjects
FG004
Lack of Efficacy
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Full Analysis Set (N=490), i.e. all participants randomized.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Participants randomized to placebo treatment for 8 weeks.
BG001
Aprocitentan 5 mg
Participants randomized to 5 mg aprocitentan treatment for 8 weeks.
BG002
Aprocitentan 10 mg
Participants randomized to 10 mg aprocitentan treatment for 8 weeks.
BG003
Aprocitentan 25 mg
Participants randomized to 25 mg aprocitentan treatment for 8 weeks.
BG004
Aprocitentan 50 mg
Participants randomized to 50 mg aprocitentan treatment for 8 weeks.
BG005
Lisinopril 20 mg
Participants randomized to 20 mg lisinopril treatment for 8 weeks.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00082
BG00182
BG00282
BG00382
BG00481
BG00581
BG006490
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
In the placebo group, one participant had out of analysis window blood pressure measurement. This participant was part of the PPS but not part of the modified Per Protocol Set (N=409).
Mean
Standard Deviation
years
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG00282
ParticipantsBG003
Sex: Female, Male
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
In the placebo group, one participant had out of analysis window blood pressure measurement. This participant was part of the PPS but not part of the modified Per Protocol Set (N=409).
Count of Participants
Participants
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Ethnicity (NIH/OMB)
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
Count of Participants
Participants
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Race (NIH/OMB)
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
Count of Participants
Participants
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Canada
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Weight
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
In the placebo group, one participant had out of analysis window blood pressure measurement. This participant was part of the PPS but not part of the modified Per Protocol Set (N=409).
Mean
Standard Deviation
kilograms
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Body Mass Index
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
In the placebo group, one participant had out of analysis window blood pressure measurement. This participant was part of the PPS but not part of the modified Per Protocol Set (N=409).
Mean
Standard Deviation
kilograms per square meter
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Duration of essential hypertension at screening
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
Mean
Standard Deviation
years
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
Antihypertensive treatment at screening
Per Protocol Set (PPS, N=410) 8 weeks in the double-blind period, and no major protocol deviation.
In the placebo group, one participant had out of analysis window blood pressure measurement. This participant was part of the PPS but not part of the modified Per Protocol Set (N=409).
Number
participants
Title
Denominators
Categories
Full Analysis Set
ParticipantsBG00082
ParticipantsBG00182
ParticipantsBG002
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 End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
The absolute change in mean trough sitting diastolic blood pressure (SiDBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the diastolic blood pressure from the start of treatment.
Modified Per-protocol set (mPPS). All participants who had a mean trough sitting diastolic blood pressure (SiDBP) at Week-8 of the double-blind treatment period and that did not have any major protocol deviation were analyzed.
Posted
Mean
Standard Deviation
mmHg
Baseline (Day 1) and end of double-blind treatment (Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
OG001
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00066
OG00168
OG00271
OG003
Title
Denominators
Categories
Baseline
Title
Measurements
OG00097.5± 5.4
OG00197.8± 5.5
OG00297.7± 4.3
OG003
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
OG002
OG003
OG004
Multiple Comparison Procedure-Modeling (MCP-Mod) was used to assess a dose-response across placebo and all aprocitentan doses. The null hypothesis of "no dose-response" was rejected if at least one of the six Multiple Contrast Tests (MCTs) had a multiplicity adjusted p-value <0.05. The analysis was performed using the R-package "DoseFinding" (Bornkamp B, Pinheiro J, Bretz F. Planning and analyzing dose finding experiments. 2016. Available from: cran.r-projects.org/web/packages/DoseFinding.)
Multiple Comparison Procedure-Modeling
<0.001
Other
Secondary
Change From Baseline to End of Double-blind Treatment in Sitting Systolic Blood Pressure at Trough
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
The absolute change in mean trough sitting systolic blood pressure (SiSBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the systolic blood pressure from the start of treatment.
Modified Per-protocol set (mPPS). All participants who had a mean trough sitting systolic blood pressure (SiSBP) at Week 8 of the double-blind treatment period and that did not have any major protocol deviation were analyzed.
Posted
Mean
Standard Deviation
mmHg
Baseline (Day 1) and end of double-blind treatment (Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks
OG001
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG002
Aprocitentan 10 mg
Secondary
Control Rates at the End of the Double-blind Treatment Period Based on Trough Sitting Diastolic and Systolic Blood Pressure
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis. The Canadian Hypertension Education Program (CHEP) issued guidelines proposing cut-offs of 85 mmHg for diastolic blood pressure and 135 mmHg for systolic blood pressure specifically focusing on measurement by automated office blood pressure measurement. The number of participants at the end of the 8-week treatment period that had values below the protocol and CHEP cut-off values are reported.
The initial protocol control rates at Week 8 (Day 56) on trough SiDBP are also reported and were defined as a SiDBP of less than 90 mmHg and a SiSBP of less than 140 mmHg.
Modified Per Protocol Set (mPPS). All participants who had diastolic and systolic blood pressure measurements at Week 8 of the double-blind treatment period and that did not have any major protocol deviation were analyzed.
Posted
Count of Participants
Participants
End of double-blind treatment (Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
OG001
Aprocitentan 5 mg
Secondary
Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Diastolic Blood Pressure
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
A participant was a responder if the reduction from baseline in mean trough sitting diastolic blood pressure (SiDBP) was 10 mmHg or greater-than 10 mmHg.
Modified Per Protocol Set (mPPS).
Posted
Count of Participants
Participants
Baseline (Day 1) and end of double-blind treatment (Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
OG001
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
Secondary
Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Systolic Blood Pressure
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
A participant was a responder if the reduction from baseline in mean trough sitting systolic blood pressure (SiSBP) was 20 mmHg or greater-than 20 mmHg.
Modified Per Protocol Set (mPPS).
Posted
Count of Participants
Participants
Baseline (Day 1) and end of double-blind treatment (Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
OG001
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
Secondary
Change From Baseline to End of Double-blind Treatment in 24-hour Diastolic and Systolic Ambulatory Blood Pressure Monitoring (ABPM)
Diastolic and systolic ambulatory blood pressure monitoring was performed over a 24-hour period with the ABPM device (Mobil-o-Graph) set to record diastolic and systolic blood pressure at a pre-defined time. Over a 24-hour period 3 measurements per hour during the day and 2 per hour during the night were made. The blood pressure measurements were derived from the area under the diastolic and systolic blood pressure curves and divided by the time span and averaged.
For ambulatory blood pressure monitoring the baseline was the period from the time of last run-in placebo intake up to the time of the first double-blind treatment intake.
All participants in a treatment group with a full set of ABPM (Ambulatory Blood Pressure Monitoring) values over the 24-hour period at baseline and at Week 8.
Posted
Mean
Standard Error
mmHg
Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
OG001
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
Secondary
Ratio of Group Mean at Trough to Group Mean at Peak for Diastolic Blood Pressure Based on Ambulatory Blood Pressure Monitoring (ABPM)
Ratio of group mean at trough to group mean at peak was calculated from the diastolic ambulatory blood pressure monitoring performed over a 24-hour period with the ABPM device. The trough (the smallest blood pressure reduction) and the peak (the highest blood pressure reduction) ratio show the extent of blood pressure lowering throughout the 24-hour dosing interval in the group.
The group mean trough (at 20-24 hours) to group mean (at 2-6 hours) peak of diastolic blood pressure were examined to evaluate the extent to which once-daily dosing criteria were met (trough-to-peak values greater than 0.5).
The ratio is positive if there was a decrease in diastolic blood pressure at both the trough and peak times at the end of treatment (Day 55 to Day 56) when compared to baseline (Day -1 to Day 1).
For ambulatory blood pressure monitoring the baseline was the period from the time of last run-in placebo intake up to the time of the first double-blind treatment intake.
All participants in a treatment group with a full set of ABPM (Ambulatory Blood Pressure Monitoring) values over the 24-hour period at baseline and at Week 8.
Posted
Number
Ratio of mean at trough to mean at peak
Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.
OG001
Other Pre-specified
Supportive Analysis of Primary Endpoint: Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough
Participants had their blood pressure measured at the study site using the BpTRU® device. The BpTRU® is an automatic unattended office blood pressure measurement device. Six measurements, at rest, per participant per visit were performed. The mean of the last 5 measurements was used for the analysis.
The absolute change in mean trough sitting diastolic blood pressure (SiDBP) measured by from baseline (i.e., at randomization) to week 8 (Day 56). A negative change indicates a decrease in the diastolic blood pressure from the start of treatment.
The Full Analysis Set (FAS) includes all participants randomized who had a baseline mean trough SiDBP. Participants were evaluated according to the study treatment they have been assigned to. Missing data was analyzed by LOCF (Last Observation Carried Forward).
Posted
Mean
Standard Deviation
mmHg
Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)
ID
Title
Description
OG000
Placebo
One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks
OG001
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
Time Frame
Up to 12 weeks after first intake of medication after randomization.
Description
The treatment-emergent adverse events were defined as those adverse events with onset on or after the first day of double-blind study treatment intake up to the last day of double-blind study treatment intake plus 30 days.
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
Placebo
Participants received placebo orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
0
82
0
82
30
82
EG001
Aprocitentan 5 mg
Participants received aprocitentan 5 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
0
82
0
82
18
82
EG002
Aprocitentan 10 mg
Participants received aprocitentan 10 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
0
82
0
82
24
82
EG003
Aprocitentan 25 mg
Participants received aprocitentan 25 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
0
82
2
82
32
82
EG004
Aprocitentan 50 mg
Participants received aprocitentan 50 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
0
81
0
81
22
81
EG005
Lisinopril 20 mg
Participants received lisinopril 20 mg orally once daily in the morning for 8 weeks during the double-blind treatment period, followed by a 2-week single-blind placebo washout period, followed by a further two-week follow-up period.
0
81
1
81
25
81
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Bundle branch block left
Cardiac disorders
MedDRA (19.0)
Non-systematic Assessment
EG0000 events0 affected82 at risk
EG0010 events0 affected82 at risk
EG0020 events0 affected82 at risk
EG0031 events1 affected82 at risk
EG0040 events0 affected81 at risk
EG0050 events0 affected81 at risk
Fall
Injury, poisoning and procedural complications
MedDRA (19.0)
Non-systematic Assessment
EG0000 events0 affected82 at risk
EG0010 events0 affected82 at risk
EG0020 events0 affected82 at risk
EG003
Jaw fracture
Injury, poisoning and procedural complications
MedDRA (19.0)
Non-systematic Assessment
EG0000 events0 affected82 at risk
EG0010 events0 affected82 at risk
EG0020 events0 affected82 at risk
EG003
Neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00066
OG00168
OG00271
OG00367
OG00468
OG00569
Title
Denominators
Categories
Baseline
Title
Measurements
OG000149.2± 13.1
OG001149.4± 13.9
OG002149.8± 12.7
OG003151.2± 13.7
OG004148.6± 12.8
OG005149.8± 14.2
Absolute Change from Baseline to Week 8
Title
Measurements
OG000-7.7± 18.8
OG001-10.3± 15.3
OG002-15.0± 14.5
OG003
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
OG002
OG003
OG004
Multiple Comparison Procedure-Modeling (MCP-Mod) was used to assess a dose-response across placebo and all aprocitentan doses. The null hypothesis of "no dose-response" was rejected if at least one of the six Multiple Contrasts Tests (MCTs) had a multiplicity adjusted p-value <0.05. The analysis was performed using the R-package "DoseFinding" (Bornkamp B, Pinheiro J, Bretz F. Planning and analyzing dose finding experiments. 2016. Available from: cran-rprojects.org/web/packages/DoseFinding.)
Multiple Comparison Procedure-Modeling
<0.001
Other
OG000
OG001
ANCOVA
with Dunnett correction.
0.7071
LS Mean
-2.45
Standard Error of the Mean
2.445
2-Sided
95
-8.44
3.54
Superiority
OG000
OG002
ANCOVA
with Dunnett correction.
0.0138
LS Mean
-7.05
Standard Error of the Mean
2.420
2-Sided
95
-12.98
-1.12
Superiority
OG000
OG003
ANCOVA
with Dunnett correction.
0.0003
LS Mean
-9.90
Standard Error of the Mean
2.457
2-Sided
95
-15.92
-3.88
Superiority
OG000
OG004
ANCOVA
with Dunnett correction.
0.0077
LS Mean
-7.58
Standard Error of the Mean
0.0077
2-Sided
95
-13.58
-1.59
Superiority
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00066
OG00168
OG00271
OG00367
OG00468
OG00569
Title
Denominators
Categories
SiDBP less than 90 mmHg
Title
Measurements
OG00022
OG00130
OG00237
OG00343
OG00439
OG00538
SiDBP less than 85 mmHg (CHEP)
Title
Measurements
OG00017
OG00115
OG00229
OG003
SiSBP less than 140 mmHg
Title
Measurements
OG00034
OG00137
OG00243
OG003
SiSBP less than 135 mmHg (CHEP)
Title
Measurements
OG00024
OG00127
OG00232
OG003
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
20 mg
Lisinopril: 20 mg capsules orally o.d. for 8 weeks
Units
Counts
Participants
OG00066
OG00168
OG00271
OG00367
OG00468
OG00569
Title
Denominators
Categories
Title
Measurements
OG00021
OG00121
OG00234
OG00340
OG00438
OG00531
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00066
OG00168
OG00271
OG00367
OG00468
OG00569
Title
Denominators
Categories
Title
Measurements
OG00016
OG00116
OG00222
OG00328
OG00422
OG00520
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00027
OG00136
OG00236
OG00330
OG00433
OG00530
Title
Denominators
Categories
Baseline 24-hour mean DBP
Title
Measurements
OG00090.46± 10.66
OG00190.60± 10.19
OG00292.60± 10.92
OG00389.28± 9.53
OG00491.53± 10.54
OG00591.18± 9.48
Absolute change in 24-hour mean DBP at Week 8
Title
Measurements
OG000-2.49± 5.52
OG001-3.76± 6.36
OG002-6.55± 7.04
OG003
Baseline 24-hour mean SBP
Title
Measurements
OG000140.28± 14.2
OG001139.90± 15.87
OG002144.30± 15.68
OG003
Absolute change in 24-hour mean SBP at Week 8
Title
Measurements
OG000-3.54± 7.46
OG001-3.16± 10.54
OG002-7.72± 11.37
OG003
Aprocitentan 5 mg
One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00027
OG00137
OG00236
OG00330
OG00433
OG00530
Title
Denominators
Categories
Title
Measurements
OG000-48.03
OG0012.59
OG0020.90
OG0031.49
OG0041.25
OG0050.65
OG002
Aprocitentan 10 mg
Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.
OG003
Aprocitentan 25 mg
One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG004
Aprocitentan 50 mg
One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.
OG005
Lisinopril 20 mg
One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan.
Units
Counts
Participants
OG00081
OG00179
OG00280
OG00377
OG00477
OG00579
Title
Denominators
Categories
Baseline
Title
Measurements
OG00098.0± 5.5
OG00197.5± 5.3
OG00297.7± 4.2
OG00398.2± 5.0
OG00498.4± 5.3
OG00596.9± 4.4
Absolute Change from Baseline to Week 8
Title
Measurements
OG000-4.2± 11.1
OG001-5.8± 8.9
OG002-9.9± 8.4
OG003
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
OG002
OG003
OG004
Multiple Comparison Procedure-Modeling (MCP-Mod) was used to assess a dose-response across placebo and all aprocitentan doses. The null hypothesis of "no dose-response" was rejected if at least one of the six Multiple Contrast Tests (MCTs) had a multiplicity adjusted p-value <0.05. The analysis was performed using the R-package "DoseFinding" (Bornkamp B, Pinheiro J, Bretz F. Planning and analyzing dose finding experiments. 2016. Available from: cran.r-projects.org/web/packages/DoseFinding.)