Inclusion Criteria:
* Adult males or nonpregnant, nonlactating females aged 18 years or older.
* Willing to abstain from other treatments for hemorrhoidal disease throughout the study, including nonprescription medications, prescription medications, and procedures. Stable-dose fiber supplements are permitted.
* Females of childbearing potential must meet the protocol-defined contraception requirements. The protocol defines childbearing potential as having a uterus and at least one ovary and not being postmenopausal. Postmenopause is defined as 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum FSH greater than 40 mIU/mL. The protocol lists the following acceptable methods or conditions: surgical sterility by bilateral oophorectomy, with or without hysterectomy, at least 6 weeks before screening; an intrauterine device in place at least 1 month before screening; barrier contraception (condom or diaphragm) with spermicide, or male-partner condom use, for at least 1 month before Day 1 and continuing throughout the study and for at least 3 days after the last dose; hormonal contraception for at least 6 weeks before Day 1 and continuing throughout the study and for at least 3 days after the last dose; or continuous abstinence from penile-vaginal intercourse for at least 1 month before Day 1 and throughout the study and for 3 days after the last dose.
* External anal skin tags are permitted. These are healed, asymptomatic tissue remnants from previously bulging internal hemorrhoids and do not preclude concomitant active hemorrhoids.
* Grade 2-3 internal hemorrhoids assessed by the Investigator using digital rectal examination and anoscopy at Day 1. Externally prolapsing internal hemorrhoids that can be manually reduced during digital rectal examination are permitted.
* At Day 1, at least two hemorrhoid-related rectal or anal symptoms of pain, burning, itching, bleeding, anal leakage, or discomfort rated "Moderate" or "Somewhat" or higher on HDSIM questions 1-8.
Exclusion Criteria:
* External hemorrhoids, described in the protocol as external to the dentate line, or Grade 4 internal hemorrhoids that cannot be manually reduced during digital rectal examination.
* Current anal fissures.
* Any hemorrhoidal procedure, such as anorectal surgery, hemorrhoidal ligation, or hemorrhoidectomy.
* Diagnosis of inflammatory bowel disease.
* Systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher. Participants receiving treatment for hypertension may participate if both readings are below these thresholds.
* Diagnosed fecal incontinence within the preceding 6 months. Fecal incontinence is distinguished from hemorrhoid-related anal leakage.
* Grade 3 or Grade 4 laboratory abnormalities according to the FDA's 2007 toxicity grading guidance for preventive vaccine trials; clinically significant Grade 1 or Grade 2 laboratory abnormalities as determined by the Investigator; or an ACTH stimulation test result outside the normal range as determined by the Supervising Endocrinologist. Examples of clinically significant conditions include uncontrolled type 1 or type 2 diabetes, uncontrolled abnormal thyroid function, impaired liver function, sclerosing cholangitis, cirrhosis or hepatic impairment, significant renal disease, thrombocytopenia, neutropenia, or active systemic infection.
* A positive serology test result at screening.
* Vaccination within 2 weeks before signing informed consent or during the study, and/or surgical or other procedures that increase exposure to pathogens.
* Systemic symptoms, melena, or a clinical presentation suggesting underlying pathology requiring diagnostic evaluation rather than symptomatic hemorrhoid treatment.
* Any active infection.
* Steroid therapy within 28 days before screening or required during the study.
* History of fissure, fistula-in-ano, abscess, arteriovenous malformations, proctalgia fugax, rectal cancer, or another pathological condition of the anus or rectum other than symptomatic internal hemorrhoids.
* Past or current pelvic radiation.
* Known hypersensitivity or allergy to hydrocortisone acetate, hydrocortisone, or any suppository component.
* Participation in another investigational clinical study within 30 days before screening or during this study.
* Previous randomization in this study. A participant may be rescreened once with Medical Monitor approval.
* Any clinically significant finding or comorbid condition, including drug or alcohol abuse, that would jeopardize participant health or safety, as determined by the Investigator.
* Use of prohibited medications without completing the protocol-required washout period.
