Dose-finding Study With ACT-132577 (Aprocitentan) in Participants With Essential Hypertension

NCT02603809 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AC-080A201
• Study Type: interventional
• Target: 1,659
• Locations: 4 countries
• Sites: 90

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.

Conditions

Essential Hypertension

Outcome Measures

Primary Outcomes (1)

• 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 (6)

• Change From Baseline to End of Double-blind Treatment in Sitting Systolic Blood Pressure at Trough

  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

  End of double-blind treatment (Day 56)

• Response Rates at End of Double-blind Treatment Period Based on Trough Sitting Diastolic Blood Pressure

  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

  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)

  Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)

Other Outcomes (1)

• Supportive Analysis of Primary Endpoint: Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough

  Baseline (Day -1 to Day 1) and end of double-blind treatment (Day 55 and Day 56)

Study Arms (6)

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.

Drug: Aprocitentan 25 mg

Aprocitentan 50 mg

EXPERIMENTAL

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

Interventions

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.

Also known as: ACT-132577

Aprocitentan 5 mg

Aprocitentan 10 mg DRUG

Two capsules of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks.

Also known as: ACT-132577

Aprocitentan 10 mg

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.

Also known as: ACT-132577

Aprocitentan 25 mg

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.

Also known as: ACT-132577

Aprocitentan 50 mg

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (90)

Appalachian Cardiovascular Associates

Fort Payne, Alabama, 35967, United States

Location

Radiant Research Inc

Chandler, Arizona, 85224, United States

Location

Warner Family Practice / Radiant Research Inc

Chandler, Arizona, 85224, United States

Location

Phoenix Medical Research Institute LLC

Peoria, Arizona, 85381, United States

Location

Advanced Arizona Clinical Research

Tucson, Arizona, 85704, United States

Location

Noble Clinical Research LLC

Tucson, Arizona, 85704, United States

Location

Desert Sun Clinical Research LLc

Tucson, Arizona, 85710, United States

Location

Advanced Research Center Inc

Anaheim, California, 92805, United States

Location

Med Center

Carmichael, California, 95608, United States

Location

John Muir Physician Network Clinical Research Center

Concord, California, 94520, United States

Location

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Long Beach Center for Clinical Research

Long Beach, California, 90807, United States

Location

Entertainment Medical Group Inc

Los Angeles, California, 90036, United States

Location

Artemis institute for Clinical Research

San Diego, California, 92103, United States

Location

Memorial Research Medical Clinic / Orange County Research Center

Tustin, California, 92780, United States

Location

Empire Clinical Research

Upland, California, 91786, United States

Location

Clinical Research Consulting LLC

Milford, Connecticut, 06460, United States

Location

Chase Medical Research LLC

Waterbury, Connecticut, 06708, United States

Location

Alfieri Cardiology

Wilmington, Delaware, 19803, United States

Location

ACRC - Cardiology

Atlantis, Florida, 33462, United States

Location

Innovative Research of West Florida INC

Clearwater, Florida, 33756, United States

Location

Avail Clinical Research LLC

DeLand, Florida, 32720, United States

Location

Alan Graff, MD, PA

Fort Lauderdale, Florida, 33308, United States

Location

Gulfcoast Clinical Research Center

Fort Myers, Florida, 33912, United States

Location

AGA Clinical Trials

Hialeah, Florida, 33012, United States

Location

Canvas Clinical Research, LLC

Lake Worth, Florida, 33467, United States

Location

LCC Medical Research Institute

Miami, Florida, 33126, United States

Location

Allied Biomedical Research Institute, INC

Miami, Florida, 33155, United States

Location

Southeast Regional Research Group

Savannah, Georgia, 31401, United States

Location

Community Clin Res CTR

Anderson, Indiana, 46011, United States

Location

Midwest Institute for Clinical Research

Indianapolis, Indiana, 46260, United States

Location

Heartland Research Associated LLC

Newton, Kansas, 67114, United States

Location

Heartland Research Associates LLC

Wichita, Kansas, 67205, United States

Location

Heartland Research Associates LLC

Wichita, Kansas, 67207, United States

Location

Avant Research Associates, LLC

Crowley, Louisiana, 70526, United States

Location

Best Clinical Trials LLC

New Orleans, Louisiana, 70115, United States

Location

New Orleans Center for Clinical Research - Nola

New Orleans, Louisiana, 70119, United States

Location

Clinsite LLC

Ann Arbor, Michigan, 48106, United States

Location

Primecare Research Associates, LLC

Florissant, Missouri, 63031, United States

Location

Clinical Research Advantage, Inc. / Diagnostic Center Of Medicine - Durango

Las Vegas, Nevada, 89117, United States

Location

Premier Research

Trenton, New Jersey, 08611, United States

Location

Rochester Clinical Research Inc.

Rochester, New York, 14609, United States

Location

Metrolina Internal Medicine/Internal Medicine Research

Charlotte, North Carolina, 28204, United States

Location

Pharmquest LLC

Greensboro, North Carolina, 27408, United States

Location

Peters Medical Research

High Point, North Carolina, 27262, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27604-1547, United States

Location

Lillestol Research LLC

Fargo, North Dakota, 58103, United States

Location

Sterling Research Group Ltd.

Cincinnati, Ohio, 45219, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43213, United States

Location

Dayton Clinical Research

Dayton, Ohio, 45406, United States

Location

Aventiv Research Inc.

Dublin, Ohio, 43016, United States

Location

Oklahoma City Clinic - Edmond / Radiant Research Inc

Edmond, Oklahoma, 73034, United States

Location

Clinical Research Advantage, Inc. / Oklahoma City Clinic - Midwest City

Midwest City, Oklahoma, 73110, United States

Location

Willamette Valley Clinical Studies

Eugene, Oregon, 97404, United States

Location

Detweiler Family Medicine and Associates PC

Lansdale, Pennsylvania, 19446, United States

Location

Suburban Research Center

Media, Pennsylvania, 19063, United States

Location

Degarmo Institute of Medical Research

Greer, South Carolina, 29651, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Tekton Research Inc

Austin, Texas, 78745, United States

Location

Texas Diabetes & Endocrinology

Austin, Texas, 78749, United States

Location

Trinity Hypertension & Metabolic Research Institute

Carrollton, Texas, 75006, United States

Location

Family Medicine Associates of Texas - ACRC Trials

Carrollton, Texas, 75010, United States

Location

Coastal Bend Clinical Research

Corpus Christi, Texas, 78413, United States

Location

TR - Global Medical Research

DeSoto, Texas, 75115, United States

Location

Ventavia Research Group, LLC

Fort Worth, Texas, 76104, United States

Location

Clinical Investigations of Texas

Plano, Texas, 75075, United States

Location

Avant Research Associates LLC

Port Arthur, Texas, 77640, United States

Location

Texas Diabetes & Endocrinology

Round Rock, Texas, 78681, United States

Location

Radiant Research Inc

San Antonio, Texas, 78229, United States

Location

Bandera Family Health Care

San Antonio, Texas, 78249, United States

Location

Wasatch Clinical Research LLC

Salt Lake City, Utah, 84107, United States

Location

Health Research of Hampton Roads

Newport News, Virginia, 23606, United States

Location

National Clinical Research Inc

Richmond, Virginia, 23294, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Manna Research - Vancouver

Vancouver, British Columbia, V6J 1S3, Canada

Location

Canadian Phase Onwards Inc

Toronto, Ontario, M3J 2C5, Canada

Location

Manna Research - Toronto

Toronto, Ontario, M9W 4L6, Canada

Location

Manna Research - Levis

Lévis, Quebec, G6W 0M6, Canada

Location

Diex Recherche Montreal Inc

Montreal, Quebec, H2Y 1S1, Canada

Location

Manna Research - Pointe Claire

Pointe-Claire, Quebec, H9R 4S3, Canada

Location

Diex Reserach Sherbrooke Inc

Sherbrooke, Quebec, J1H 1Z1, Canada

Location

Cardiology Department Barzilai

Ashkelon, 78278, Israel

Location

Soroka University Hospital - Hypertension Unit

Beersheba, 84101, Israel

Location

The Hyper Unit, Edith Wolfson Medical Center

Holon, 58100, Israel

Location

Hypertension Treatment Center, Internal Dep, Hadassah

Jerusalem, 91240, Israel

Location

Hypertension And Nephrology Department, Meir Medical Center

Kefar Sava, 44261, Israel

Location

Clinical Research Unit Kaplan Medical Center

Rehovot, 76100, Israel

Location

Internal Med Department A, Ziv Medical Center

Safed, 13100, Israel

Location

Advanced Medical Concepts, PSC

Cidra, 00739, Puerto Rico

Location

Research & Cardiovascular Corp.

Ponce, 00717, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 32063059 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

aprocitentan; Lisinopril

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Clinical Trial Disclosure Desk
• Organization: Idorsia Pharmaceuticals Ltd

clinical-trials-disclosure@idorsia.com

+41 58 844 19 77

Study Officials

• ClinicalTrials

  Idorsia Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2015
• First Posted: November 13, 2015
• Study Start: December 14, 2015
• Primary Completion: February 28, 2017
• Study Completion: April 7, 2017
• Last Updated: November 23, 2022
• Results First Posted: April 13, 2020

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7); PR (2); IL (7); US (74)