Internal Hemorrhoids
Conditions
Brief summary
A randomized, double-blind, placebo-controlled, multicenter, parallel group study of the safety and efficacy of Hydrocortisone Acetate Suppositories, 25 mg compared to placebo suppositories in the treatment of symptomatic internal hemorrhoids.
Detailed description
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.
Interventions
DRUGHydrocortisone Acetate Suppository, 25 mg (Nivagen)
One (1) Hydrocortisone Acetate Suppository, 25 mg is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days).
DRUGPlacebo (Vehicle) Suppository (Nivagen)
One (1) Placebo (Vehicle) Suppository is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days).
Sponsors
Nivagen Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
India, United States
Participant flow
Recruitment details
Mostly patients were recruited from the existing database
Participants by arm
| Arm | Count |
|---|---|
| Hydrocortisone Acetate Suppository, 25 mg One (1) Hydrocortisone Acetate Suppository, 25 mg is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days).
Hydrocortisone Acetate Suppository, 25 mg: One (1) Hydrocortisone Acetate Suppository, 25 mg is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days). | 51 |
| Placebo (Vehicle) Suppository One (1) Placebo (Vehicle) Suppository is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days).
Placebo (Vehicle) Suppository: One (1) Placebo (Vehicle) Suppository is inserted into the anal canal twice daily (morning and evening) for 2 weeks (14 days). | 52 |
| Total | 103 |
Baseline characteristics
| Characteristic | Hydrocortisone Acetate Suppository, 25 mg | Placebo (Vehicle) Suppository | Total |
|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 15.43 | 50.8 years STANDARD_DEVIATION 15.57 | 50.6 years STANDARD_DEVIATION 15.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 22 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 30 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Itching severity | 2.15 Scores on a scale STANDARD_DEVIATION 0.49 | 2.12 Scores on a scale STANDARD_DEVIATION 0.5 | 2.13 Scores on a scale STANDARD_DEVIATION 0.5 |
| Region of Enrollment India | 21 Participants | 22 Participants | 43 Participants |
| Region of Enrollment United States | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Female | 20 Participants | 25 Participants | 45 Participants |
| Sex: Female, Male Male | 31 Participants | 27 Participants | 58 Participants |
| Swelling of hemorrhoid | 2.9 scores on a scale STANDARD_DEVIATION 0.68 | 2.8 scores on a scale STANDARD_DEVIATION 0.6 | 2.85 scores on a scale STANDARD_DEVIATION 0.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 |
| other Total, other adverse events | 1 / 50 | 2 / 51 |
| serious Total, serious adverse events | 0 / 50 | 0 / 51 |
Outcome results
Primary
Reduction in Itching Severity
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
Time frame: Day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone Acetate Suppository, 25 mg | Reduction in Itching Severity | 0.74 scores on a scale | Standard Deviation 0.56 |
| Placebo (Vehicle) Suppository | Reduction in Itching Severity | 0.71 scores on a scale | Standard Deviation 0.61 |
Comparison: The statistical analyses were conducted using SAS software Version 9.4.All statistical tests were two-sided at a significance level of α = 0.05. Continuous data were presented using descriptive statistics (i.e. number of subjects, mean, SD, median, minimum, and maximum).Baseline value of each assessment was defined as the latest available assessment obtained prior to the first administration of the study drug.p-value: 0.8323t-test, 2 sided
Primary
Reduction in Swelling
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.
Time frame: Day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocortisone Acetate Suppository, 25 mg | Reduction in Swelling | 2.3 scores on a scale | Standard Deviation 0.74 |
| Placebo (Vehicle) Suppository | Reduction in Swelling | 2.0 scores on a scale | Standard Deviation 0.68 |
Comparison: The statistical analyses were conducted using SAS software Version 9.4.All statistical tests were two-sided at a significance level of α = 0.05. Continuous data were presented using descriptive statistics (i.e. number of subjects, mean, SD, median, minimum, and maximum).Baseline value of each assessment was defined as the latest available assessment obtained prior to the first administration of the study drug.p-value: 0.8918t-test, 2 sided