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Essential HypertensionPhase 2NCT02603809

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

A Phase 2 study testing Aprocitentan 5 mg, Aprocitentan 10 mg and Aprocitentan 25 mg in people with Essential Hypertension, run by Idorsia Pharmaceuticals Ltd. at 90 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Essential Hypertension
What is being tested?
Aprocitentan 5 mg, Aprocitentan 10 mg and Aprocitentan 25 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,659 participants
Where
90 sitesin 4 countries
Study dates
14 Dec 2015to 7 Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

90 sites in 4 countries.

90 sites in 4 countries

United States74 sites

  • Advanced Research Center Inc

    Anaheim, California, 92805

  • Community Clin Res CTR

    Anderson, Indiana, 46011

  • Clinsite LLC

    Ann Arbor, Michigan, 48106

  • ACRC - Cardiology

    Atlantis, Florida, 33462

  • Tekton Research Inc

    Austin, Texas, 78745

  • Texas Diabetes & Endocrinology

    Austin, Texas, 78749

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • Med Center

    Carmichael, California, 95608

  • Trinity Hypertension & Metabolic Research Institute

    Carrollton, Texas, 75006

  • Family Medicine Associates of Texas - ACRC Trials

    Carrollton, Texas, 75010

  • Radiant Research Inc

    Chandler, Arizona, 85224

  • Warner Family Practice / Radiant Research Inc

    Chandler, Arizona, 85224

  • Metrolina Internal Medicine/Internal Medicine Research

    Charlotte, North Carolina, 28204

  • Sterling Research Group Ltd.

    Cincinnati, Ohio, 45219

  • Innovative Research of West Florida INC

    Clearwater, Florida, 33756

  • Aventiv Research Inc.

    Columbus, Ohio, 43213

  • John Muir Physician Network Clinical Research Center

    Concord, California, 94520

  • Coastal Bend Clinical Research

    Corpus Christi, Texas, 78413

  • Avant Research Associates, LLC

    Crowley, Louisiana, 70526

  • Dayton Clinical Research

    Dayton, Ohio, 45406

  • Avail Clinical Research LLC

    DeLand, Florida, 32720

  • TR - Global Medical Research

    DeSoto, Texas, 75115

  • Aventiv Research Inc.

    Dublin, Ohio, 43016

  • Oklahoma City Clinic - Edmond / Radiant Research Inc

    Edmond, Oklahoma, 73034

  • Willamette Valley Clinical Studies

    Eugene, Oregon, 97404

  • Lillestol Research LLC

    Fargo, North Dakota, 58103

  • Primecare Research Associates, LLC

    Florissant, Missouri, 63031

  • Alan Graff, MD, PA

    Fort Lauderdale, Florida, 33308

  • Gulfcoast Clinical Research Center

    Fort Myers, Florida, 33912

  • Appalachian Cardiovascular Associates

    Fort Payne, Alabama, 35967

  • Ventavia Research Group, LLC

    Fort Worth, Texas, 76104

  • Pharmquest LLC

    Greensboro, North Carolina, 27408

  • Degarmo Institute of Medical Research

    Greer, South Carolina, 29651

  • AGA Clinical Trials

    Hialeah, Florida, 33012

  • Peters Medical Research

    High Point, North Carolina, 27262

  • Midwest Institute for Clinical Research

    Indianapolis, Indiana, 46260

  • Volunteer Research Group

    Knoxville, Tennessee, 37920

  • Canvas Clinical Research, LLC

    Lake Worth, Florida, 33467

  • Detweiler Family Medicine and Associates PC

    Lansdale, Pennsylvania, 19446

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

    Las Vegas, Nevada, 89117

  • Clinical Trials Research

    Lincoln, California, 95648

  • Long Beach Center for Clinical Research

    Long Beach, California, 90807

  • Entertainment Medical Group Inc

    Los Angeles, California, 90036

  • Suburban Research Center

    Media, Pennsylvania, 19063

  • LCC Medical Research Institute

    Miami, Florida, 33126

  • Allied Biomedical Research Institute, INC

    Miami, Florida, 33155

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

    Midwest City, Oklahoma, 73110

  • Clinical Research Consulting LLC

    Milford, Connecticut, 06460

  • Best Clinical Trials LLC

    New Orleans, Louisiana, 70115

  • New Orleans Center for Clinical Research - Nola

    New Orleans, Louisiana, 70119

  • Health Research of Hampton Roads

    Newport News, Virginia, 23606

  • Heartland Research Associated LLC

    Newton, Kansas, 67114

  • Phoenix Medical Research Institute LLC

    Peoria, Arizona, 85381

  • Clinical Investigations of Texas

    Plano, Texas, 75075

  • Avant Research Associates LLC

    Port Arthur, Texas, 77640

  • Wake Research Associates

    Raleigh, North Carolina, 27604-1547

  • National Clinical Research Inc

    Richmond, Virginia, 23294

  • Rochester Clinical Research Inc.

    Rochester, New York, 14609

  • Texas Diabetes & Endocrinology

    Round Rock, Texas, 78681

  • Wasatch Clinical Research LLC

    Salt Lake City, Utah, 84107

  • Radiant Research Inc

    San Antonio, Texas, 78229

  • Bandera Family Health Care

    San Antonio, Texas, 78249

  • Artemis institute for Clinical Research

    San Diego, California, 92103

  • Southeast Regional Research Group

    Savannah, Georgia, 31401

  • Premier Research

    Trenton, New Jersey, 08611

  • Advanced Arizona Clinical Research

    Tucson, Arizona, 85704

  • Noble Clinical Research LLC

    Tucson, Arizona, 85704

  • Desert Sun Clinical Research LLc

    Tucson, Arizona, 85710

  • Memorial Research Medical Clinic / Orange County Research Center

    Tustin, California, 92780

  • Empire Clinical Research

    Upland, California, 91786

  • Chase Medical Research LLC

    Waterbury, Connecticut, 06708

  • Heartland Research Associates LLC

    Wichita, Kansas, 67205

  • Heartland Research Associates LLC

    Wichita, Kansas, 67207

  • Alfieri Cardiology

    Wilmington, Delaware, 19803

Other trials in United States

Canada7 sites

  • Manna Research - Levis

    Lévis, Quebec, G6W 0M6

  • Diex Recherche Montreal Inc

    Montreal, Quebec, H2Y 1S1

  • Manna Research - Pointe Claire

    Pointe-Claire, Quebec, H9R 4S3

  • Diex Reserach Sherbrooke Inc

    Sherbrooke, Quebec, J1H 1Z1

  • Canadian Phase Onwards Inc

    Toronto, Ontario, M3J 2C5

  • Manna Research - Toronto

    Toronto, Ontario, M9W 4L6

  • Manna Research - Vancouver

    Vancouver, British Columbia, V6J 1S3

Other trials in Canada

Israel7 sites

  • Cardiology Department Barzilai

    Ashkelon, 78278

  • Soroka University Hospital - Hypertension Unit

    Beersheba, 84101

  • The Hyper Unit, Edith Wolfson Medical Center

    Holon, 58100

  • Hypertension Treatment Center, Internal Dep, Hadassah

    Jerusalem, 91240

  • Hypertension And Nephrology Department, Meir Medical Center

    Kefar Sava, 44261

  • Clinical Research Unit Kaplan Medical Center

    Rehovot, 76100

  • Internal Med Department A, Ziv Medical Center

    Safed, 13100

Other trials in Israel

Puerto Rico2 sites

  • Advanced Medical Concepts, PSC

    Cidra, 00739

  • Research & Cardiovascular Corp.

    Ponce, 00717

Other trials in Puerto Rico

About this study

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).

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.

Read the 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.

Being tested
Aprocitentan 5 mg, Aprocitentan 10 mg, Aprocitentan 25 mg, Aprocitentan 50 mg, Lisinopril 20 mg
Medical subject headings
Essential Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aprocitentan 5 mgDrug

    Also called ACT-132577

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

  • Aprocitentan 10 mgDrug

    Also called ACT-132577

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

  • Aprocitentan 25 mgDrug

    Also called ACT-132577

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

  • Aprocitentan 50 mgDrug

    Also called ACT-132577

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

  • Lisinopril 20 mgDrug

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

  • PlaceboDrug

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

Study groups in NCT02603809
Study groupRoleWhat they receive
PlaceboPlacebo comparatorAfter 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.
Receives: Drug: Placebo
Aprocitentan 5 mgExperimentalAfter 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.
Receives: Drug: Aprocitentan 5 mg
Aprocitentan 10 mgExperimentalAfter 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.
Receives: Drug: Aprocitentan 10 mg
Aprocitentan 25 mgExperimentalAfter 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.
Receives: Drug: Aprocitentan 25 mg
Aprocitentan 50 mgExperimentalAfter 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.
Receives: Drug: Aprocitentan 50 mg
Lisinopril 20 mgActive comparatorAfter 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.
Receives: Drug: Lisinopril 20 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline (Day 1) and end of double-blind treatment (Day 56)

Secondary outcomes (6)

  1. 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.

    Measured: Baseline (Day 1) and end of double-blind treatment (Day 56)

  2. 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.

    Measured: End of double-blind treatment (Day 56)

  3. 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.

    Measured: Baseline (Day 1) and end of double-blind treatment (Day 56)

  4. 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.

    Measured: Baseline (Day 1) and end of double-blind treatment (Day 56)

  5. 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.

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

  6. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2015 (estimated)
  2. Study start14 Dec 2015
  3. Primary completion28 Feb 2017
  4. Study completion7 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,659 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02603809
Sponsor's protocol ID
AC-080A201
Status last verified
Nov 2022
First submitted
9 Nov 2015
Last updated
23 Nov 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32063059

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aprocitentan 5 mg, Aprocitentan 10 mg and Aprocitentan 25 mg in people with Essential Hypertension, run by Idorsia Pharmaceuticals Ltd. at 90 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 90 sites in United States, Canada, Israel, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to End of Double-blind Treatment in Sitting Diastolic Blood Pressure at Trough (time frame: Baseline (Day 1) and end of double-blind treatment (Day 56)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02603809, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2022.

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