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

NCT ID: NCT02603809

Last Updated: 2022-11-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

1659 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-14

Study Completion Date

2017-04-07

Brief Summary

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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

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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

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Essential Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.

Aprocitentan 5 mg

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.

Group Type EXPERIMENTAL

Aprocitentan 5 mg

Intervention Type DRUG

One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.

Aprocitentan 10 mg

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.

Group Type EXPERIMENTAL

Aprocitentan 10 mg

Intervention Type DRUG

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

Aprocitentan 25 mg

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.

Group Type EXPERIMENTAL

Aprocitentan 25 mg

Intervention Type DRUG

One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.

Aprocitentan 50 mg

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.

Group Type EXPERIMENTAL

Aprocitentan 50 mg

Intervention Type DRUG

One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.

Lisinopril 20 mg

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.

Group Type ACTIVE_COMPARATOR

Lisinopril 20 mg

Intervention Type DRUG

One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan

Interventions

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Aprocitentan 5 mg

One capsule of 5 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.

Intervention Type DRUG

Aprocitentan 10 mg

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

Intervention Type DRUG

Aprocitentan 25 mg

One capsule of 25 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.

Intervention Type DRUG

Aprocitentan 50 mg

One capsule of 50 mg aprocitentan, orally, once daily in the morning for 8 weeks, along with placebo capsule matching lisinopril.

Intervention Type DRUG

Lisinopril 20 mg

One capsule of 20 mg lisinopril, orally, once daily in the morning for 8 weeks, along with placebo capsule matching aprocitentan

Intervention Type DRUG

Placebo

One capsule each of placebo matching aprocitentan and placebo matching lisinopril orally, once daily in the morning for 8 weeks.

Intervention Type DRUG

Other Intervention Names

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ACT-132577 ACT-132577 ACT-132577 ACT-132577

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ClinicalTrials

Role: STUDY_DIRECTOR

Idorsia Pharmaceuticals

Locations

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Appalachian Cardiovascular Associates

Fort Payne, Alabama, United States

Site Status

Radiant Research Inc

Chandler, Arizona, United States

Site Status

Warner Family Practice / Radiant Research Inc

Chandler, Arizona, United States

Site Status

Phoenix Medical Research Institute LLC

Peoria, Arizona, United States

Site Status

Advanced Arizona Clinical Research

Tucson, Arizona, United States

Site Status

Noble Clinical Research LLC

Tucson, Arizona, United States

Site Status

Desert Sun Clinical Research LLc

Tucson, Arizona, United States

Site Status

Advanced Research Center Inc

Anaheim, California, United States

Site Status

Med Center

Carmichael, California, United States

Site Status

John Muir Physician Network Clinical Research Center

Concord, California, United States

Site Status

Clinical Trials Research

Lincoln, California, United States

Site Status

Long Beach Center for Clinical Research

Long Beach, California, United States

Site Status

Entertainment Medical Group Inc

Los Angeles, California, United States

Site Status

Artemis institute for Clinical Research

San Diego, California, United States

Site Status

Memorial Research Medical Clinic / Orange County Research Center

Tustin, California, United States

Site Status

Empire Clinical Research

Upland, California, United States

Site Status

Clinical Research Consulting LLC

Milford, Connecticut, United States

Site Status

Chase Medical Research LLC

Waterbury, Connecticut, United States

Site Status

Alfieri Cardiology

Wilmington, Delaware, United States

Site Status

ACRC - Cardiology

Atlantis, Florida, United States

Site Status

Innovative Research of West Florida INC

Clearwater, Florida, United States

Site Status

Avail Clinical Research LLC

DeLand, Florida, United States

Site Status

Alan Graff, MD, PA

Fort Lauderdale, Florida, United States

Site Status

Gulfcoast Clinical Research Center

Fort Myers, Florida, United States

Site Status

AGA Clinical Trials

Hialeah, Florida, United States

Site Status

Canvas Clinical Research, LLC

Lake Worth, Florida, United States

Site Status

LCC Medical Research Institute

Miami, Florida, United States

Site Status

Allied Biomedical Research Institute, INC

Miami, Florida, United States

Site Status

Southeast Regional Research Group

Savannah, Georgia, United States

Site Status

Community Clin Res CTR

Anderson, Indiana, United States

Site Status

Midwest Institute for Clinical Research

Indianapolis, Indiana, United States

Site Status

Heartland Research Associated LLC

Newton, Kansas, United States

Site Status

Heartland Research Associates LLC

Wichita, Kansas, United States

Site Status

Heartland Research Associates LLC

Wichita, Kansas, United States

Site Status

Avant Research Associates, LLC

Crowley, Louisiana, United States

Site Status

Best Clinical Trials LLC

New Orleans, Louisiana, United States

Site Status

New Orleans Center for Clinical Research - Nola

New Orleans, Louisiana, United States

Site Status

Clinsite LLC

Ann Arbor, Michigan, United States

Site Status

Primecare Research Associates, LLC

Florissant, Missouri, United States

Site Status

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

Las Vegas, Nevada, United States

Site Status

Premier Research

Trenton, New Jersey, United States

Site Status

Rochester Clinical Research Inc.

Rochester, New York, United States

Site Status

Metrolina Internal Medicine/Internal Medicine Research

Charlotte, North Carolina, United States

Site Status

Pharmquest LLC

Greensboro, North Carolina, United States

Site Status

Peters Medical Research

High Point, North Carolina, United States

Site Status

Wake Research Associates

Raleigh, North Carolina, United States

Site Status

Lillestol Research LLC

Fargo, North Dakota, United States

Site Status

Sterling Research Group Ltd.

Cincinnati, Ohio, United States

Site Status

Aventiv Research Inc.

Columbus, Ohio, United States

Site Status

Dayton Clinical Research

Dayton, Ohio, United States

Site Status

Aventiv Research Inc.

Dublin, Ohio, United States

Site Status

Oklahoma City Clinic - Edmond / Radiant Research Inc

Edmond, Oklahoma, United States

Site Status

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

Midwest City, Oklahoma, United States

Site Status

Willamette Valley Clinical Studies

Eugene, Oregon, United States

Site Status

Detweiler Family Medicine and Associates PC

Lansdale, Pennsylvania, United States

Site Status

Suburban Research Center

Media, Pennsylvania, United States

Site Status

Degarmo Institute of Medical Research

Greer, South Carolina, United States

Site Status

Volunteer Research Group

Knoxville, Tennessee, United States

Site Status

Tekton Research Inc

Austin, Texas, United States

Site Status

Texas Diabetes & Endocrinology

Austin, Texas, United States

Site Status

Trinity Hypertension & Metabolic Research Institute

Carrollton, Texas, United States

Site Status

Family Medicine Associates of Texas - ACRC Trials

Carrollton, Texas, United States

Site Status

Coastal Bend Clinical Research

Corpus Christi, Texas, United States

Site Status

TR - Global Medical Research

DeSoto, Texas, United States

Site Status

Ventavia Research Group, LLC

Fort Worth, Texas, United States

Site Status

Clinical Investigations of Texas

Plano, Texas, United States

Site Status

Avant Research Associates LLC

Port Arthur, Texas, United States

Site Status

Texas Diabetes & Endocrinology

Round Rock, Texas, United States

Site Status

Radiant Research Inc

San Antonio, Texas, United States

Site Status

Bandera Family Health Care

San Antonio, Texas, United States

Site Status

Wasatch Clinical Research LLC

Salt Lake City, Utah, United States

Site Status

Health Research of Hampton Roads

Newport News, Virginia, United States

Site Status

National Clinical Research Inc

Richmond, Virginia, United States

Site Status

Northwest Clinical Research Center

Bellevue, Washington, United States

Site Status

Manna Research - Vancouver

Vancouver, British Columbia, Canada

Site Status

Canadian Phase Onwards Inc

Toronto, Ontario, Canada

Site Status

Manna Research - Toronto

Toronto, Ontario, Canada

Site Status

Manna Research - Levis

Lévis, Quebec, Canada

Site Status

Diex Recherche Montreal Inc

Montreal, Quebec, Canada

Site Status

Manna Research - Pointe Claire

Pointe-Claire, Quebec, Canada

Site Status

Diex Reserach Sherbrooke Inc

Sherbrooke, Quebec, Canada

Site Status

Cardiology Department Barzilai

Ashkelon, , Israel

Site Status

Soroka University Hospital - Hypertension Unit

Beersheba, , Israel

Site Status

The Hyper Unit, Edith Wolfson Medical Center

Holon, , Israel

Site Status

Hypertension Treatment Center, Internal Dep, Hadassah

Jerusalem, , Israel

Site Status

Hypertension And Nephrology Department, Meir Medical Center

Kefar Sava, , Israel

Site Status

Clinical Research Unit Kaplan Medical Center

Rehovot, , Israel

Site Status

Internal Med Department A, Ziv Medical Center

Safed, , Israel

Site Status

Advanced Medical Concepts, PSC

Cidra, , Puerto Rico

Site Status

Research & Cardiovascular Corp.

Ponce, , Puerto Rico

Site Status

Countries

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United States Canada Israel Puerto Rico

References

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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.

Reference Type DERIVED
PMID: 32063059 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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AC-080A201

Identifier Type: -

Identifier Source: org_study_id

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