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

Inclusion Criteria

• 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 ( 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.

Exclusion Criteria

• Resting trough seated SBP ≥180 or 4.8 mmol/L;
• Compliance with medications (including both open-label placebo and current antihypertensive medications) 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)