Efficacy and Safety Study to Treat Subjects With Symptomatic Internal Hemorrhoids

Internal Hemorrhoids Clinical Trial

— VEN309  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01355874
• Other study ID #: VEN 309-Hem-SE3-001
• Status: Terminated
• Phase: Phase 3
• First received: May 16, 2011
• Last updated: January 26, 2014
• Start date: July 2011
• Est. completion date: June 2012

Study information

• Verified date: July 2012
• Source: Ventrus Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 403
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhoids
• Internal Hemorrhoids

Intervention

Drug:
• Iferanserin
0.5% iferanserin ointment (containing 10 mg of iferanserin) BID for 14 days during double blind.
• Placebo
Placebo ointment BID for 14 days during double blind.
• Iferanserin + Placebo
0.5% iferanserin ointment (containing 10 mg of iferanserin) BID for 7 days followed by placebo ointment BID for 7 days during the double blind.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ventrus Biosciences, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		7 days
Secondary	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).		7 days