Evaluate Safety and Efficacy of 25 mg Hydrocortisone Acetate Suppositories in Treatment of Internal Hemorrhoids

STUDY DESIGN:

25 mg hydrocortisone suppositories administered twice daily compared to a vehicle placebo in approximately 100 subjects with symptomatic internal hemorrhoids. Subjects will be randomized in a 1:1 ratio (Test product: placebo).

The study will consist of 2 periods:

1. Treatment Period (2 weeks/ Days 1-14)
2. Follow-up Period (2 weeks/ Days 15-28)

The visits are as follows:

Visit 1 (Day 1 Baseline/Randomization) Visit 2 (Day 8±1, Interim Visit) Visit 3 (Day 15±2, End of Treatment Visit) Visit 4 (Day 29±3, End of Study Visit)

ENDPOINTS:

1. Clinician Reported Outcome (ClinRO) - Anoscopy (Visits 1, 3). Anoscopy - Visual assessment of hemorrhoids. Video of the procedure will be recorded for blinded central reading and assessment
2. Patient Reported Outcome: Subjects will use Daily Diaries to record the time and date of each medication application, concomitant medication and adverse events. The subjects will complete the Subject Questionnaire at Visits 1, 2, 3 and 4 (or early termination) and daily between visits.

• Hydrocortisone Acetate Suppository, 25 mg (Nivagen) (Drug): One (1) Hydrocortisone Acetate Suppository, 25 mg is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days).
• Placebo (Vehicle) Suppository (Nivagen) (Drug): One (1) Placebo (Vehicle) Suppository is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days).

Primary outcomes

• Reduction in Swelling [Day 15]: Reduction in the swelling of internal hemorrhoid was measured by anoscopy. Visual assessment of hemorrhoids was performed at end of treatment. Video of the procedure will be recorded for blinded central reading and assessment. Swelling was graded on a scale from "0 - None" to "4 - Very Severe". Numeric grades and their changes from baseline are summarized descriptively by visit and treatment group. Changes from baseline will be compared between the treatment groups. Mean difference between the groups and its 95% confidence interval will be displayed at Visit 4, along with the p-value from the two-sample t-test.
• Reduction in Itching Severity [Day 15]: Patient-reported outcome (PRO) was collated and analyzed by deploying the Internal Hemorrhoid Sign and Symptom Assessment (IHSSA) questionnaire. The patients updated the questionnaire on a daily basis between visits 1-5. Responses to each item were averaged across each period. The mean score from the Screening period was considered the baseline score. Mean scores and their changes from baseline were summarized. Itching was scored from on 0-4 scale (0 =No itching, 1 = A little itching, 2 =Moderate itching, 3 = A lot of itching, 4 = Worst itching that you could imagine

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* internal hemorrhoids.
* hemorrhoidal bleeding.
* male or female aged 18 years and older.
* willing to forego the use of non-prescription (OTC) and prescription medication or procedures for the treatment of hemorrhoidal disease and/or pain for the duration of the study.
* agree to not change their diet during the study.

Exclusion Criteria:

* external hemorrhoids.
* using other OTC or prescription medications for treatment of hemorrhoidal disease and/or pain.
* pregnant or nursing female.
* received systemic glucocorticoids within the last 2 months prior to starting study.
* participated in an investigational drug study within 30 days prior to baseline.

Participant flow

Outcome results

• Reduction in Swelling (Primary), Mean, scores on a scale: Hydrocortisone Acetate Suppository, 25 mg 2.3 +/- 0.74; Placebo (Vehicle) Suppository 2.0 +/- 0.68 (p 0.8918)
• Reduction in Itching Severity (Primary), Mean, scores on a scale: Hydrocortisone Acetate Suppository, 25 mg 0.74 +/- 0.56; Placebo (Vehicle) Suppository 0.71 +/- 0.61 (p 0.8323)

Adverse events

Time frame: Total time period for which AE data was collected was ~6 weeks for each subject

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2019-04-26)

• Anand Shukla, MS, MBA,, Study director, Nivagen Pharmaceuticals