Clinical trial NCT01355874: Efficacy and Safety Study to Treat Subjects With Symptomatic Internal Hemorrhoids
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Treatment Group, Multicenter Efficacy and Safety Study of Intra-Anal Application of Iferanserin (10 mg) as a 0.5% Ointment in Subjects With Symptomatic Internal Hemorrhoids
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Internal Hemorrhoids
Keywords: Internal Symptomatic Hemorrhoids
Lead sponsor: Ventrus Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2011-05-18
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the effect of iferanserin ointment on cessation of bleeding when administered intra-anally twice daily (BID) for 7 or 14 days in subjects with symptomatic internal hemorrhoids.

Methodology:

Double-Blind: Phase 3, multicenter, double-blind, randomized, parallel group, placebo-controlled part of the study. Extension: Multicenter, open-label part of the study.

Study Treatment Duration:

Double-Blind: 28 days (14-day treatment period and a 14-day follow-up period). Extension: 12 months (open-label part of the study in which there will be a scheduled visit every three months. Subjects who have recurrence(s) of their symptomatic internal hemorrhoids will be treated with open-label iferanserin for 7 days followed by a 21-day follow-up period).

Criteria for Evaluation:

Primary Endpoint:

The primary endpoint is the cessation of bleeding by the end of Day 7 that persists for the remainder of the treatment period (through Day 14).

Detailed description: Primary Objective:

To evaluate the effect of iferanserin ointment on cessation of bleeding when administered intra-anally twice daily (BID) for 7 or 14 days in subjects with symptomatic internal hemorrhoids. Safety Secondary Objective To determine the safety of iferanserin ointment administered intra-anally BID for 7 or 14 days in subjects with symptomatic internal hemorrhoids.

Exploratory Objectives:

To evaluate the frequency of recurrence of bleeding in subjects with symptomatic internal hemorrhoids. To evaluate time to bleeding recurrence in subjects with symptomatic internal hemorrhoids. To evaluate efficacy of iferanserin ointment in the treatment of recurrence when administered intra-anally BID for 7 days in subjects with symptomatic internal hemorrhoids. To evaluate the parameters of the Symptom Satisfaction Questionnaire

Methodology:

Double-Blind: Phase 3, multicenter, double-blind, randomized, parallel group, placebo-controlled part of the study. Extension: Multicenter, open-label part of the study.

Criteria for Evaluation:

Primary Endpoint:

The primary endpoint is the cessation of bleeding by the end of Day 7 that persists for the remainder of the treatment period (through Day 14).

Secondary Endpoints:

Key Secondary Endpoints Cessation of itching by the end of Day 7 that persists for the remainder of the treatment period (through Day 14). Cessation of pain by the end of Day 7 that persists for the remainder of the treatment period (through Day 14). Safety Secondary Endpoints Adverse events (AEs). Serious Adverse events (SAEs). Physical examination. Hematology, serum chemistry, and urinalysis. Vital signs. Electrocardiogram.

Exploratory Endpoints:

Bleeding recurrence rate of symptomatic internal hemorrhoids. Time to bleeding recurrence of symptomatic internal hemorrhoids. Response to open-label iferanserin ointment in the treatment of recurrence of symptomatic internal hemorrhoids. Overall improvement score for the parameters of the Symptom Satisfaction Questionnaire.

Eligibility criteria: 1.1 Inclusion Criteria for Double-Blind and Recurrence

1. Males or non-pregnant females, aged ≥ 18 to ≤ 75 years.
2. Symptomatic internal hemorrhoids, Grades I-III by direct anoscopic visualization (anoscopic visualization not required if Grade determined by colonoscopy within 28 days prior to Day 1).
3. Bleeding from hemorrhoids for two consecutive days prior to randomization (Day 1).

   • For females experiencing menses, on the two days prior to randomization they must confirm that blood is from the anus and not from their menses by gently inserting a cotton swab into the anus after attempting a bowel movement; and they must see blood on the cotton swab for the two consecutive days prior to randomization to meet the inclusion criteria.
4. Itching OR pain for two consecutive days prior to randomization (Day 1).
5. Able to attempt bowel movements daily (defined as trying to have a bowel movement while sitting on the toilet for at least a few minutes, at least once daily, whether or not you feel the need to have a bowel movement that day).
6. Body mass index of ≥ 18.5 to ≤ 36 kg/m2.
7. Female of non-childbearing potential, including any female who: a) has had a hysterectomy, b) has had a bilateral oophorectomy, c) has had a bilateral tubal ligation or d) is post menopausal (demonstration of total cessation of menses for ≥ 1 year from the date of the screening visit).
8. Females of child bearing potential who agree to use two forms of contraception, one of which must be a barrier method, during the full duration of the study.
9. Able to communicate adequately with the investigator and to comply with the requirements for the entire study.
10. Capable of using the IVRS and adequately communicate comprehension of IVRS questions to the investigator.
11. Capable of and freely willing to provide written informed consent prior to participating in the study.

1. 1.2 Exclusion Criteria for Double-Blind and Recurrence

1. Grade IV internal hemorrhoids.
2. Age ≥ 40 years, with no complete colon evaluation within three years.
3. Age \< 40 years, with no sigmoidoscopy or complete colon evaluation within three years.
4. Age \< 40 years, with any of the following and no complete colon evaluation within two years; or age ≥ 40 years, with any of the following and no complete colon evaluation within one year:

   * History of adenomatous polyps.
   * Family history of either colorectal cancer or colorectal adenomas diagnosed in a first-degree relative before age 60.
   * Family history or genetic testing indicating the presence of one of two hereditary syndromes.
5. Malignancy within 5 years prior to Day 1(with the exception of treated basal cell/squamous cell carcinoma of the skin).
6. History of inflammatory bowel disease.
7. History of irritable bowel syndrome with constipation or diarrhea.
8. Previous surgical or instrumental treatment of internal hemorrhoids.
9. Clinical evidence or history of fecal incontinence.
10. Current thrombosed internal or external hemorrhoid(s).
11. Clinical evidence or history of anal fissure.
12. Clinical evidence or history of anal fistula.
13. AST/ALT \> 3x ULN.
14. Hemoglobin \< 10.0 g/dL.
15. Selective serotonin reuptake inhibitors within 28 days prior to Day 1.
16. Tamoxifen within 28 days prior to Day 1.
17. Laxatives (unless maintained on a stable dose of the medication for ≥ 60 days prior to Day 1).
18. Anticoagulants (e.g., coumadin, heparinoids, dabigatran) within 90 days prior to Day 1.
19. Anti-platelet agents or low dose aspirin (unless maintained on the medication for ≥ 90 days prior to Day 1).
20. Over the counter or prescription anti-hemorrhoid agents (including herbal supplements) within 14 days prior to Day 1.
21. Topical anesthetics within 14 days prior to Day 1.
22. Chronic use of analgesics (e.g., opioids, acetaminophen, aspirin, NSAIDS, cox-2 inhibitors, etc).
23. Any investigational agents within 28 days prior to Day 1 (with the exception of iferanserin for recurrence).
24. Anti-TNF agents within 6 months prior to Day 1.
25. Oral or parenteral steroids within 28 days prior to Day 1.
26. Use of anal, intra-anal, or intra-rectal steroids within 28 days prior to Day 1.
27. Expected to have a planned interventional and/or surgical procedure that requires hospitalization, colonoscopy, or sigmoidoscopy (colonoscopy or sigmoidoscopy during the screening period is acceptable).
28. Following concomitant disease state:

    * Clinical evidence or history of significant cardiovascular disease including arrhythmias, clinically significant ECG abnormalities, myocardial infarction, stroke, congestive heart failure (greater than class II), and valve disease or abnormalities.
    * Asthma currently requiring treatment (with the exception of infrequent use of rescue inhaler).
    * Clinical evidence or history of chronic renal failure (greater than Stage III).
    * Clinical evidence or history of gastric ulcer, duodenal ulcer, or pancreatitis.
    * Clinical evidence or history of hematological disease.
    * Clinical evidence or history of neurological disease.
    * Acute infection currently requiring treatment.
    * Clinical evidence or history of chronic infectious disease.
29. Major organ transplant.
30. Any disease or prior surgery that may interfere with the subject successfully completing the study.
31. History of any prior anal or rectal surgery (hemorrhoid banding with the 5 years of Day 1).
32. Psychosis, schizophrenia, mania, depressive disorders, history of suicide attempt or suicidal ideation, or any other psychiatric illness (with the exception of intermittent anxiety).
33. Known sensitivity to investigational product(s) or class of investigational product(s).
34. Drug or alcohol abuse within 12 months of Day 1.
35. Currently using narcotic(s) chronically.
36. Breast-feeding females.
37. Females on their menstrual cycle who cannot discern whether the bleeding is rectal bleeding or vaginal bleeding from menstruation.
38. Employees, family members, or students of the investigator or clinical site.

Primary outcomes:
measure: Proportion of subjects with cessation of bleeding by the end of Day 7 that persists for the remainder of the treatment period (through Day 14) will be analyzed as the primary endpoint
timeFrame: 7 days
Secondary outcomes:
measure: Proportion of subjects with cessation of pain by the end of Day 7 that persists for the remainder of the treatment period (through Day 14).
timeFrame: 7 days
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health
state: Alabama
city: Huntsville
country: United States
facility: Clinical Research Associates
state: Alabama
city: Phoenix
country: United States
facility: Comprehensive Health Services
state: Arizona
city: Tucson
country: United States
facility: Adobe
state: Arizona
city: Tucson
country: United States
facility: Desert Sun Clin Res
state: Arizona
city: Sherwood
country: United States
facility: AR Gastro
state: Arkansas
city: Anaheim
country: United States
facility: ACRI
state: California
city: Burbank
country: United States
facility: Providence Clin Res
state: California
city: Carmichael
country: United States
facility: Med Center
state: California
city: Laguna Hills
country: United States
facility: South Orange County Surgical Group
state: California
city: Lomita
country: United States
facility: Torrence C. R.
state: California
city: Long Beach
country: United States
facility: Premiere Clin Res
state: California
city: Mission Hills
country: United States
facility: Facey Med Foundation
state: California
city: Montebello
country: United States
facility: Futura Research
state: California
city: Orange
country: United States
facility: Community Clin Trials
state: California
city: Reseda
country: United States
facility: Del Carmen Med Center
state: California
city: San Diego
country: United States
facility: MARG
state: California
city: San Diego
country: United States
facility: Med Center for Clinical Research
state: California
city: Westlake Village
country: United States
facility: Westlake Res
state: California
city: Salida
country: United States
facility: Colorado Research
state: Colorado
city: Clearwater
country: United States
facility: Innovative
state: Florida
city: DeLand
country: United States
facility: Avail Clin Res
state: Florida
city: Hilieah
country: United States
facility: Eastern
state: Florida
city: Hollywood
country: United States
facility: Center for GI Disorders
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clin Res
state: Florida
city: Jupiter
country: United States
facility: Jupiter Research
state: Florida
city: Miami
country: United States
facility: Aplusresearch
state: Florida
city: Miami
country: United States
facility: Kendall
state: Florida
city: Miami
country: United States
facility: MRA
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastro Assoc
state: Florida
city: Sanford
country: United States
facility: ICR
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Columbus
country: United States
facility: Southeast REgional Research Group
state: Georgia
city: Hartwell
country: United States
facility: Tri County
state: Georgia
city: Savannah
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Overland
country: United States
facility: Pinnacle Med Inst
state: Kansas
city: Lexington
country: United States
facility: Kentucy med Center
state: Kentucky
city: Marrerro
country: United States
facility: Praetorian Pharmaceutical Res
state: Louisiana
city: Metarie
country: United States
facility: Clinical Trials Mgmt
state: Louisiana
city: Monroe
country: United States
facility: Delta Research
state: Louisiana
city: New Orleans
country: United States
facility: Women Under Study
state: Louisiana
city: Chevy Chase
country: United States
facility: Capital Digestive
state: Maryland
city: Hagerstown
country: United States
facility: Meritus Center for Clin Res
state: Maryland
city: Hollywood
country: United States
facility: Mid Atlantic Res Center
state: Maryland
city: Saginaw
country: United States
facility: Saginaw Med Res
state: Michigan
city: Wyoming
country: United States
facility: Gastro Assoc Western Michigan
state: Michigan
city: Jackson
country: United States
facility: Gastrointestinal Associates
state: Mississippi
city: Lee's Summitt
country: United States
facility: Midwest Center for Clin Res
state: Missouri
city: Mexico
country: United States
facility: Center for Digestive & Liver Diseases
state: Missouri
city: Las Vegas
country: United States
facility: Clin Res Nevada
state: Nevada
city: Marlton
country: United States
facility: S. Jersey Gastro
state: New Jersey
city: Great Neck
country: United States
facility: Long Island GI Group
state: New York
city: New York
country: United States
facility: MRA NY
state: New York
city: Asheville
country: United States
facility: Ashville Gastro
state: North Carolina
city: Davidson
country: United States
facility: Carolinas Res Ass
state: North Carolina
city: Greenboro
country: United States
facility: Vital
state: North Carolina
city: Harrisburg
country: United States
facility: Carolinas Research
state: North Carolina
city: Raleigh
country: United States
facility: Wake Res
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Hightop Med Res
state: Ohio
city: Dayton
country: United States
facility: Dayton Gastro
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastro
state: Ohio
city: Norman
country: United States
facility: Central Sooner
state: Oklahoma
city: Chattanooga
country: United States
facility: Clinsearch
state: Tennessee
city: Germantown
country: United States
facility: Memphis Gastro
state: Tennessee
city: Hermitage
country: United States
facility: Assoc of Gastro
state: Tennessee
city: Nashville
country: United States
facility: Dial Research
state: Tennessee
city: Nashville
country: United States
facility: First Clinic
state: Tennessee
city: Fort Worth
country: United States
facility: Texas Health Research
state: Texas
city: Houston
country: United States
facility: Amcare Research
state: Texas
city: Houston
country: United States
facility: Houston Gastro
state: Texas
city: Odessa
country: United States
facility: Permian
state: Texas
city: Sugarland
country: United States
facility: Pioneer Research
state: Texas
city: Ogden
country: United States
facility: ARI
state: Utah
city: Sandy
country: United States
facility: ARI
state: Utah
city: Christianburg
country: United States
facility: New River Valley Res
state: Virginia
city: Lyncburg
country: United States
facility: Blue Ridge Medical Center
state: Virginia
Study officials:
affiliation: Cleveland Clinic Weston, FL
name: Cleveland Clinic
role: PRINCIPAL_INVESTIGATOR
References: