Phase 2b Study of KBP-5074 in Subjects With Uncontrolled Hypertension and Advanced Chronic Kidney Disease

NCT03574363 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: KBP5074-2-001
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 2 randomized, double-blind, placebo-controlled, multi-center study to assess the efficacy, safety, and pharmacokinetics of KBP-5074 in patients with moderate-to-severe chronic kidney disease and uncontrolled hypertension.

Conditions

Chronic Kidney Diseases; Hypertension

Keywords

Chronic Kidney Disease; Hypertension

Outcome Measures

Primary Outcomes (1)

• Systolic Blood Pressure

  Change in trough cuff resting seated SBP from baseline to Day 84.

  Baseline to Day 84

Secondary Outcomes (2)

• Diastolic Blood Pressure

  Baseline to Day 84

• UACR

  Baseline to Day 84

Other Outcomes (1)

• Total KBP-5074 Concentration

  Day 84

Study Arms (3)

KBP-5074 0.25 mg tablet

EXPERIMENTAL

KBP-5074 0.25 mg tablet QD orally, 84 days

Drug: KBP-5074 0.25 mg tablet

KBP-5074 0.5 mg tablet

EXPERIMENTAL

KBP-5074 0.5 mg tablet QD orally, 84 days

Drug: KBP-5074 0.5 mg tablet

Placebo tablet

PLACEBO COMPARATOR

Placebo tablet QD orally, 84 days

Drug: KBP-5074 0.25 mg tablet; Drug: KBP-5074 0.5 mg tablet

Interventions

KBP-5074 0.5 mg tablet DRUG

Oral administration, QD, 84 days

Also known as: MRA

KBP-5074 0.5 mg tablet; Placebo tablet

KBP-5074 0.25 mg tablet DRUG

Oral administration, QD, 84 days

Also known as: MRA

KBP-5074 0.25 mg tablet; Placebo tablet

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, between 18 and 85 years of age, inclusive. The lower age limit may be higher if it is legally required in the participating country;
• Body mass index between 19 and 45 kg/m2, inclusive;
• Stage 3B/4 CKD (defined as eGFR 15 and 44 mL/min/1.73 m2, based on the isotope dilution mass spectrometry traceable MDRD equation version 4, according to central laboratory results at Screening \[single retest is allowed\]);
• Uncontrolled hypertension (Grade 1 to 2 systolic hypertension - ESC/ESH), defined as:
• Resting trough cuff seated SBP 140 and 179 mmHg based on the mean of at least 2 current consecutive clinic blood pressure readings at Screening and at the end of the placebo run-in period (Visit 3); AND
• Currently on 2 or more antihypertensive medications, which have been titrated upward as tolerated to recommended hypertension target doses (such as diuretics \[except for potassium-sparing diuretics\], renin angiotensin system blockers, and/or calcium channel blockers. One of the antihypertensive medications must be high ceiling diuretic (loop or thiazide like), unless there is a documented intolerance or contraindication to diuretic therapy. The doses of the antihypertensive medications should be stable without any dose adjustment during the 30 days prior to randomization; OR
• Patients with uncontrolled hypertension and moderate-to-severe CKD with documented history of intolerance to multiple antihypertensive medications on fewer than 2 antihypertensive medications;
• Serum potassium 4.8 mmol/L at both Screening and the end of the placebo run-in period. A single retest is allowed to exclude laboratory error or hemolyzed samples;
• Women of childbearing potential (WOCBP) must agree to use 2 medically accepted, effective methods of birth control during the study and for 90 days after the end of the study. Adequate methods of contraception are defined as those that result in a low failure rate (\< 1% per year) when used consistently and correctly. Such methods include the use of oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products (such as an intrauterine diaphragm, condoms, or spermicides);
• WOCBP are defined as women who are not surgically or chemically sterilized, including hysterectomy or bilateral oophorectomy (tubal ligation is not acceptable), and who are between menarche and 1-year post-menopause; and
• Post-menopausal is defined as amenorrheic for at least 1 year, AND if aged under 60 years, have a serum follicle-stimulating hormone (FSH) level \> 20 mIU/L. Women who are taking hormone replacement therapy (HRT) do not have to have FSH assessments, but the amenorrhea (before starting HRT) must have been naturally (spontaneously) occurring and have been accompanied by an appropriate clinical profile (eg, age appropriate and history of vasomotor symptoms);
• Males with partners who are WOCBP must agree to use condoms plus spermicide and their female partner must also be using contraception (eg, hormonal or intra-uterine device). This double contraception must be used from the first dose of study drug until at least 90 days after the last dose of study drug;
• Males must also refrain from donating sperm during the study and for 90 days after the last dose; and
• Capable of understanding the written informed consent, provide signed and witnessed written informed consent before any study-specific procedure, and agree to comply with protocol requirements.

You may not qualify if:

• Resting trough seated SBP ≥180 or \< 140 mmHg, based on the mean of at least 2 current consecutive clinic blood pressure readings at Screening and the end of the placebo run-in period (Visit 3);
• Serum potassium \> 4.8 mmol/L;
• Compliance with medications (including both open-label placebo and current antihypertensive medications) \< 80% or \> 120% during the run-in period (assessed at Visit 3);
• Currently on an MRA (eg, spironolactone or eplerenone) other than KBP-5074, or received any MRAs during the last 3 months prior to Screening, or currently on any potassium supplements;
• Chronic or intermittent use of a potassium binder for the treatment of hyperkalemia from 3 months prior to Screening until the end of study assessments, including but not limited to calcium polystyrene sulfonates (eg, sorbisterit, calcium resonium), sodium polystyrene sulfonates (eg, kayexalate, anti-kalium sodium), and patiromer (eg, Veltassa™) and sodium zirconium cyclosilicate (eg, Lokelma™);
• Have routinely or chronically used or required potassium-sparing diuretics (eg, amiloride, triamterene) within 3 months prior to Screening until the end of study assessments;
• History of known/suspected contraindications, allergy, or intolerance to MRAs (eg, spironolactone, eplerenone) or has a known hypersensitivity to KBP-5074, other MRAs, or related compounds;
• Clinically significant hyperkalemia while on an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, direct renin inhibitor, and/or MRA, requiring down titration or discontinuation of above medication, or hospitalization for hyperkalemia within 3 months prior to Screening, or hyperkalemia \> 5.6 mmol/L during the 2 weeks prior to Screening;
• History/diagnosis of renal artery stenosis or history/diagnosis of renovascular hypertension;
• Currently receiving HD, or peritoneal dialysis within 3 months prior to Screening, and those patients with an episode of acute kidney injury within 3 months of Screening;
• History of a renal transplant, or impending renal transplant;
• Acute decompensated heart failure including exacerbation of chronic heart failure manifested by signs and symptoms that may require hospitalization and/or intravenous diuretic therapy (New York Heart Association Class III to IV) within 3 months prior to Screening, or presence of hemodynamically significant valve diseases and/or other hemodynamically significant obstructive lesions of left ventricular outflow tract;
• Major cardiac, cerebral, and/or carotid artery diseases, including but not limited to acute coronary syndrome, myocardial infarction, stroke, and/or transient ischemic attack; major cardiovascular or percutaneous procedures including cardiac ablation, coronary revascularization, and carotid angioplasty within 6 months prior to Screening; OR
• \- Cardiovascular conditions likely to require surgical or percutaneous intervention within 6 months from Screening;
• History of clinically significant arrhythmia, including but not limited to any of the following:

Sponsors & Collaborators

• KBP Biosciences: lead
• Worldwide Clinical Trials: collaborator

Study Sites (2)

KBP Biosciences USA Inc

Princeton, New Jersey, 08540, United States

Location

Worldwide Clinical Trials

Morrisville, North Carolina, 27560, United States

Location

Related Publications (2)

• Bakris G, Pergola PE, Delgado B, Genov D, Doliashvili T, Vo N, Yang YF, McCabe J, Benn V, Pitt B; BLOCK-CKD Study Group. Effect of KBP-5074 on Blood Pressure in Advanced Chronic Kidney Disease: Results of the BLOCK-CKD Study. Hypertension. 2021 Jul;78(1):74-81. doi: 10.1161/HYPERTENSIONAHA.121.17073. Epub 2021 May 10.

  PMID: 33966452 DERIVED

• Bakris G, Yang YF, Pitt B. Mineralocorticoid Receptor Antagonists for Hypertension Management in Advanced Chronic Kidney Disease: BLOCK-CKD Trial. Hypertension. 2020 Jul;76(1):144-149. doi: 10.1161/HYPERTENSIONAHA.120.15199. Epub 2020 Jun 10.

  PMID: 32520623 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertension

Interventions

KBP-5074; Tablets

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Kimberly Miller
• Organization: KBP Biosciences USA, Inc.

kimberly.miller@kbpbiosciences.com

4847644862

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: July 2, 2018
• Study Start: April 25, 2018
• Primary Completion: August 5, 2020
• Study Completion: August 5, 2020
• Last Updated: December 30, 2025
• Results First Posted: March 21, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)