efficacy and safety of kbp-5074 in uncontrolled hypertension and moderate or severe chronic kidney disease (ckd)

Conditions: Chronic Kidney Diseases

Summary: this phase 3, randomized, double-blind, placebo-controlled, 2-arm, parallel-group, multicenter study with randomized withdrawal will evaluate the efficacy, safety, and durability of kbp-5074 in adult participants who have stage 3b/4 chronic kidney disease (ckd) (estimated glomerular filtration rate \[egfr\] calculated using the chronic kidney disease epidemiology collaboration \[ckd-epi\] formula \[egfr {epi}\] ≥15 to ≤44 ml/min/1.73 m\^2) and uncontrolled hypertension (systolic blood pressure (sbp) ≥140 and \<180 mm hg and taking 2 or more antihypertensive medications.

participants in this study will be recruited, screened, and enrolled at approximately 140 study sites globally. the study will consist of the following periods: 1. pretreatment phase: this will include prescreening assessment and screening period of up to 4 weeks and 2-week open-label placebo run-in period. 2. a 24-week double-blind treatment period (randomization to week 24) will include: an initial 12-week (randomization to week 12) and second 12-week (week 12 to week 24) treatment period and a second 12-week treatment period (week 12 to week 24), during both the periods study drug will be titrated. 3. a 24-week open-label treatment period (week 24 to week 48) during which eligible participants will receive open-label kbp-5074. 4. a 4-week randomized double-blind withdrawal period (week 48 to week 52) during which eligible participants will be randomized to continue their current kbp-5074 dose at the end of open-label treatment or receive matching placebo for 4 weeks. 5. a 4-week post-treatment follow-up period (week 52 to week 56). during, 24-week double-blind treatment period, 24-week open-label treatment period, and at 4-week randomized double-blind withdrawal period, the background antihypertensive medications change may or may not be allowed. at double-blind treatment period, eligible participants will be randomly assigned in a 1:1 ratio to kbp-5074 0.25 mg or matching placebo once daily (qd). at the randomized double-blind withdrawal period, participants who meet the randomized withdrawal criteria will be randomly assigned in a 1:1 ratio to continue their current kbp-5074 dose at the end of the open-label treatment period or matching placebo qd.

Eligibility criteria:
inclusion criteria: * body mass index (bmi) must be ≥19 to \<45 kg/m\^2 at the screening visit * participant must have uncontrolled hypertension defined as meeting both of the following criteria: * the participant has a resting seated trough cuff sbp ≥140 mm hg at the screening visit (visit 1), and at the start (visit 2) and end (visit 3) of the run-in period * the participant is taking 2 or more antihypertensive medications that have been titrated upward as tolerated to hypertension target doses per local soc and have been stable (i.e., without any dose adjustments) from 4 weeks before the screening visit (visit 1) through the end of the run-in period (visit 3) * the participant must have stage 3b (egfr \[epi\] ≥30 and ≤44 ml/min/1.73 m\^2) or stage 4 (egfr \[epi\] ≥15 and \<30 ml/min/1.73 m\^2) ckd. exclusion criteria: * participant has a resting seated trough cuff sbp ≥180 mm hg at the screening visit (visit 1) or at the start (visit 2) or end (visit 3) of the run-in period * participant has a serum potassium level \>4.8 mmol/l during the screening or run-in periods * participant has had a serum potassium level \>5.6 mmol/l within 2 weeks before the screening visit (visit 1) * participant has been hospitalized for hyperkalemia within the 3 months before the randomization visit (visit 3) * participant was not compliant with taking placebo during the run-in period or participant was not compliant with background antihypertensive medications during the run-in period as assessed at the randomization visit (visit 3) * participant has taken an mineralocorticoid receptor antagonist (mra), a potassium-sparing diuretic, or chronic potassium supplements during the 4 weeks before the screening visit (visit 1) * participant has taken potassium binders for the treatment of hyperkalemia during the 3 months before the screening visit (visit 1) * participant has taken a strong cytochrome p450 (cyp) cyp3a4 inducer or strong cyp3a4 inhibitor during the 7 days before the randomization visit (visit 3) * participant has taken a prohibited traditional chinese medication during the 28 days prior to screening visit (visit 1). * participant was administered any other investigational product within 4 weeks or 5 half-lives (whichever is longer) prior to the screening visit (visit 1).

Keywords: stage 3b/4 chronic kidney disease hypertension uncontrolled hypertension blood pressure mineralocorticoid receptor antagonist randomized withdrawal