A Research Study to Show Aprocitentan is Efficacious and Safe to Treat Patients With Uncontrolled Blood Pressure and Chronic Kidney Disease. (INSPIRE-CKD)

Multi-center, Blinded, Randomized Study With Aprocitentan in Subjects With Uncontrolled Blood Pressure and Chronic Kidney Disease Stage 3 or 4.

The purpose of this research study is to show the blood pressure lowering effect of aprocitentan, a new drug, when added to the background antihypertensive therapy in patients with uncontrolled blood pressure and chronic kidney disease (CKD) stage 3 or 4. Participation in the research study will last up to 21 weeks (about 5 months).

Study Overview

• Status: Withdrawn
• Conditions: Hypertension; Renal Insufficiency, Chronic
• Intervention / Treatment: Drug: Aprocitentan 25 mg; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior treatment with at least 2 anti-hypertensive medications, at optimal or best tolerated dose, of different pharmacological classes, including a diuretic,
• Participants with uncontrolled blood pressure (mean sitting systolic blood pressure of 140 mmHg or greater) and chronic kidney disease stage 3 or 4 (estimated Glomerular Filtration Rate of at least 15 and below 60 mL/min/1.73m2 using the Chronic Kidney Disease-Epidemiology equation),

• Women of childbearing potential are eligible only if the following applies:

  • Negative pregnancy test at the screening visit and at baseline (i.e., end of run-in period).
  • Agree to undertake pregnancy tests during the study and up to 30 days after randomized study treatment discontinuation.
  • Agree to use highly-effective methods of contraception up to at least 30 days after study treatment discontinuation.

Exclusion Criteria:

• Mean sitting systolic blood pressure above 170 mmHg measured by "automated office blood pressure measurement" (AOBPM),
• Mean sitting diastolic blood pressure above 105 mmHg measured by AOBPM,
• Change in renal function requiring hospitalization, documented eGFR decline of greater than 20% in the 3 months prior to the screening visit, dialysis in the 3 months before the screening visit,
• Planned dialysis or kidney transplant during the course of this study,
• Nephrotic syndrome defined as urine albumin-to-creatinine ratio above 3000 mg/g,
• Known and documented chronic heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Drug: Placebo; Matching placebo tablet, oral use once daily
Experimental: Aprocitentan 25 mg	Drug: Aprocitentan 25 mg; Tablet, oral use once daily; Other Names: ACT-132577
Experimental: Aprocitentan 25 mg or Placebo	Drug: Aprocitentan 25 mg; Tablet, oral use once daily; Other Names: ACT-132577; Drug: Placebo; Matching placebo tablet, oral use once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline to Week 4 of double-blind treatment in mean trough sitting systolic blood pressure measured by automated office blood pressure measurement.	From baseline to Week 4 after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 4 of double-blind treatment in mean trough sitting diastolic blood pressure measured by automated office blood pressure measurement.		From baseline to Week 4 after treatment initiation
Ratio to baseline of urine albumin-to-creatinine ratio (UACR) at Week 4	Evaluated in the subgroup of participants with a UACR greater than 30 mg/g at baseline.	From baseline to Week 4 after treatment initiation

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Collaborators: Janssen Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): July 15, 2021

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Chronic kidney disease
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: ID-080A305; 2018-003819-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No