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

The primary purpose of the study is to assess the effect of lorundrostat taken orally (po) once a day on the Apnea-Hypopnea Index (AHI) in participants with moderate to severe obstructive sleep apnea (OSA) and hypertension.

The study is a randomized, double-blind (DB), placebo controlled, crossover study. A 3-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 of age 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.

Eligibility Criteria:
Inclusion Criteria:

1. Body mass index (BMI) ≥ 27 kilograms per meter square (kg/m\^2)
2. Previously diagnosed with moderate-to-severe OSA
3. AHI ≥15 events per hour (/hr) prior to Randomization
4. AOBP SBP of ≥130 and less than or equal to (≤) 160 millimeter of mercury (mmHg) and AOBP diastolic blood pressure (DBP) ≥60 and ≤110 mmHg
5. Participants on CPAP or PAP therapy are eligible provided they are on PAP for ≥4 hours per night and for at least 3 months prior to the study enrollment
6. Participants not currently on PAP therapy, and not anticipated to start PAP for the duration of the study
7. 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:

1. 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
2. Participants on a glucagon-like peptide-1 (GLP-1) agonist.
3. Any planned surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy during trial participation.
4. Have diagnosis of central or mixed sleep apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration
5. Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia
6. Use of bilevel positive airway pressure (BiPAP) therapy.
7. History of clinically significant hyponatremia within 1 year prior to Screening
8. eGFR less than (\<) 45 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2) at Screening
9. History of clinically relevant medical, behavioral, or psychiatric disorder, other than OSA, that is associated with insomnia or excessive sleepiness
10. Diagnosed with Child-Pugh Class C
11. Participants who regularly use caffeine stimulants or participants who are unwilling to reduce intake to 300 mg per day (approximately 3 cups of coffee), 1 week prior to Screening
12. Treatment with MRAs and/or epithelial sodium channel (ENaC) inhibitors within 1 month of the Screening Visit
13. Use of supplemental oxygen
14. Women who are pregnant, plan to become pregnant, or are breastfeeding
15. Hospitalization for the treatment of urgent or emergent hypertension within 1 year prior to Screening
16. Unstable or currently symptomatic cardiovascular disease or hospitalization in the 6 months prior to Screening
17. Previously diagnosed, recurrent orthostatic hypotension
18. Current night-shift worker or anticipated to become a night-shift worker for 3 days continuously during the duration of the study
19. Classified as a New York Heart Association (NYHA) Class III or IV at the Screening Visit