A Study to Assess the Efficacy and Safety of Lorundrostat in Participants With Obstructive Sleep Apnea and Hypertension

The study is a randomized, double-blind (DB), placebo controlled, crossover study. A 4-week screening period is followed by two DB 4-week treatment periods separated by a 2-week washout period. Participants must be 18 to 75 years old with moderate to severe OSA, hypertension and meet all applicable eligibility criteria. Participants who are medically prescribed and deemed compliant with positive airway pressure (PAP) therapy for greater than or equal to (>=) 4 hours per night (Continuous PAP [CPAP], or automatic PAP [autoPAP]) and for at least 3 months prior to the study enrollment are eligible for the study. Participants on PAP therapy should comply with PAP therapy for the duration of the study. Participants who are not currently on PAP therapy and not anticipated to start PAP for the duration of the study, are also eligible for the study.

Inclusion criteria

• Body mass index (BMI) ≥ 27 kilograms per meter square (kg/m^2)
• Previously diagnosed with moderate-to-severe OSA
• AHI ≥15 events per hour (/hr) prior to Randomization
• AOBP SBP of ≥130 and less than or equal to (≤) 180 millimeter of mercury (mmHg) and AOBP diastolic blood pressure (DBP) ≥60 and ≤110 mmHg
• Participants on CPAP or PAP therapy are eligible provided they are on PAP for ≥4 hours per night (documented) and for at least 3 months prior to the study enrollment (documented)
• Participants not currently on PAP therapy, and not anticipated to start PAP for the duration of the study
• Fertile male and female participants of childbearing potential, and their partners, must agree to use protocol-defined methods of highly effective contraception from the Screening Visit until 28 days after the last dose of study drug

Exclusion criteria

• Type 2 diabetes mellitus (T2DM) with a glycosylated hemoglobin (HbA1c) greater than (>) 9 percent (%) (>74.9 millimoles per mol [mmol/mol]) at the Screening Visit or history of diabetic ketoacidosis in the 6 months prior to the Screening Visit
• Participants on a glucagon-like peptide-1 (GLP-1) agonist.
• Any surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy within 3 months prior to Screening, or planned during participation in the study or within 1 month of the last study visit.
• Have diagnosis of central or mixed sleep apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration
• Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia
• Use of bilevel positive airway pressure (BiPAP) therapy.
• eGFR less than (<) 45 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at Screening using serum creatinine or cystatin-C
• History of clinically relevant medical, behavioral, or psychiatric disorder, other than OSA, that is associated with insomnia or excessive sleepiness
• Diagnosed with Child-Pugh Class C
• Participants who regularly use caffeine stimulants or participants who are unwilling to reduce intake to 300 mg per day (approximately 3 cups of coffee), for a period of at least 3 days prior to the Screening visit or a sleep study
• Treatment with MRAs and/or epithelial sodium channel (ENaC) inhibitors within 1 month of the Screening Visit
• Requirement for nocturnal use of supplemental oxygen
• Women who are pregnant, plan to become pregnant, or are breastfeeding
• Unstable or currently symptomatic cardiovascular disease or hospitalization in the 6 months prior to Screening
• Previously diagnosed, recurrent orthostatic hypotension
• Current night-shift worker or anticipated to become a night-shift worker for 3 days continuously during the duration of the study.