Efficacy and Safety Study With Diltiazem Hydrochloride Cream to Treat Anal Fissures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01690221
Recruitment Status : Completed
First Posted : September 21, 2012
Last Update Posted : January 23, 2014
Information provided by (Responsible Party):
Ventrus Biosciences, Inc

Brief Summary:
The purpose of this study is to determine if the study drug, VEN307 (diltiazem hydrochloride cream) is safe and to see if it will help with treatment of pain associated with anal fissures.

Condition or disease Intervention/treatment Phase
Chronic Anal Fissures Drug: VEN 307 Drug: Placebo Phase 3

Detailed Description:

Primary Objective:

To evaluate the efficacy of diltiazem hydrochloride cream on reduction of worst anal fissure (AF)-related pain associated with or following defecation when administered three times a day (TID) for 28 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 434 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3B, Randomized, Double-Blind, Placebo-Controlled, Parallel-Treatment Group, Multicenter Efficacy and Safety Study of Topical Diltiazem Hydrochloride 2% Cream in Subjects With Anal Fissure
Study Start Date : October 2012
Actual Primary Completion Date : December 2013
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: VEN 307
diltiazem hydrochloride 2% cream
Drug: VEN 307
VEN307 applied three times a day, in and around the anus, for 28 days.
Other Name: diltiazem hydrochloride 2% cream
Placebo Comparator: Placebo
Placebo Cream
Drug: Placebo
Placebo cream applied three times a day, in and around the anus, for 28 days.
Other Name: Placebo cream

Primary Outcome Measures :
  1. Change from baseline (average NRS during the last 3 days in which subject had a defecation during the 7 day screening period) in average of worst AF-related pain associated with or following defecation for Days 22-28 (Week 4). [ Time Frame: 28 days ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males or females, aged ≥ 18 to ≤ 75 years.
  2. Subjects with evidence of a circumscribed fissure, with induration at the edges.
  3. Subjects with AF-related pain associated with or following defecation occurring at least 2 times a week for at least 28 days prior to signing the informed consent form (ICF).
  4. AF-related pain associated with or following defecation of at least 5 on an 11-point numerical rating score scale (NRS) at the last defecation prior to signing the ICF (0 being no pain; 10 being the worst possible pain).
  5. Average AF-related pain associated with or following defecation of at least 5 on an 11-point NRS during the last 3 days in which subject had a defecation during the 7 days prior to randomization.
  6. Any 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 screening visit).
  7. Females of child bearing potential who agree to use at least one form of contraception (may be a barrier method), during the full duration of the study.
  8. Able to communicate adequately with the investigator and to comply with the requirements for the entire study.
  9. Capable of using the IVRS and able to adequately communicate comprehension of the IVRS questions to the investigator.
  10. Capable of and freely willing to provide written informed consent prior to participating in the study.

Exclusion Criteria:

  1. Unwilling to have visual or medical examination of the AF.
  2. More than 1 AF.
  3. Subjects with AF associated with or caused by other conditions, including but not limited to: drug-induced, trauma, HIV infection, fistula-in-ano, inflammatory bowel disease, perianal sepsis or malignancy.
  4. Unwilling to stop all other concomitant topical preparations applied in and around the anus from signing of ICF through Day 29 of the study.
  5. Use of glyceryl trinitrate (GTN) ointment for 7 days (continuous or not) in the 28 days prior to signing the ICF.
  6. Unwilling to discontinue use of sitz baths for up to 4 hours after each application of investigational product from signing of ICF to end of study.
  7. Unwilling to discontinue use of anesthetics from signing the ICF to end of study.
  8. Subfissure injection of botulinum toxin in the 3 months prior to signing the ICF.
  9. Known sensitivity to investigational product(s) or calcium channel blockers.
  10. Previous treatment with diltiazem hydrochloride cream or any other topical calcium channel blockers.
  11. Active treatment with anti-viral therapies for HIV (e.g. indinavir, nelfinivir, ritonavir).
  12. Treatment with any of the following medications within 14 days prior to signing the ICF:

    • Amitriptyline
    • Benzodiazepines
    • β-adrenoceptor antagonists (Beta-Blockers)
    • Buspirone
    • Calcium channel blockers
    • Carbamazepine
    • Cimetidine
    • Cyclosporin
    • Digoxin
    • Investigational agents
    • Lovastatin
    • Opioids
    • Pregabalin
    • Quinidine
    • Rifampin
  13. Following concomitant disease state:

    • Sick sinus syndrome except in the presence of a functioning ventricular pacemaker.
    • Second-or third-degree AV block except in the presence of a functioning ventricular pacemaker.
    • Hypotension (less than 90 mm Hg systolic).
    • Acute myocardial infarction and pulmonary congestion documented by x-ray.
    • History of bipolar disorder, psychosis, schizophrenia, mania, suicide attempt or suicidal ideation, or any other significant psychiatric illness (with the exception of intermittent anxiety) per investigator judgment.
    • History of clinically significant renal disease per investigator judgment.
    • History of clinically significant Alzheimer's or Parkinson's disease per investigator judgment.
    • History of clinically significant hepatic disease per investigator judgment.
    • Current infection treated with a macrolide antibiotic.
    • Clinical evidence or history of fecal incontinence.
    • Clinical evidence or history of anal fistula.
    • Clinical evidence or history of anal abscess.
    • History of inflammatory bowel disease (e.g. Crohn's disease, Ulcerative Colitis).
    • History of any prior anal or rectal surgery including but not limited to: lateral sphincterotomy and anal stretch (with the exception of hemorrhoidal banding and laser surgery).
    • Grade 4 hemorrhoids.
    • Chronic constipation.
  14. History of radiation therapy to the pelvis.
  15. Fixed anal stenosis/fibrosis.
  16. Major organ transplant.
  17. Any clinically significant laboratory abnormalities during screening per investigator judgment.
  18. Body Mass Index (BMI) > 40 kg/m2
  19. Malignancy within 5 years prior to randomization (with the exception of treated basal cell/squamous cell carcinoma of the skin).
  20. Any disease or prior/planned surgery that may interfere with the subject successfully completing the study.
  21. Currently using narcotic(s).
  22. Breast-feeding females.
  23. Employees, family members, or students of the investigator or clinical site.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01690221

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United States, Alabama
The Crawford Clinic
Anniston, Alabama, United States, 36207
Surgical Association of Mobile
Mobile, Alabama, United States, 36607
University of South Alabama
Mobile, Alabama, United States, 36617
Montgomery Women's Health Association, PC
Montgomery, Alabama, United States, 36117
United States, Arizona
Mayo Clinic - Arizona
Phoenix, Arizona, United States, 85054
Desert Sun Clinical Research, LLC
Tucson, Arizona, United States, 85710
United States, California
Arrowhead Regional Medical Center
Colton, California, United States, 92324
UC San Diego
La Jolla, California, United States, 92093
Alliance Research Centers
Laguna Hills, California, United States, 92653
Axis Clinical Trials
Los Angeles, California, United States, 90036
Cedars Sinai
Los Angeles, California, United States, 90048
Gastrointestinal Biosciences
Los Angeles, California, United States, 90067
University of California - Irvine Medical Center
Orange, California, United States, 92868
Digestive Care Associated, A Medical Corporation
San Carlos, California, United States, 94070
West Coast Clinical Research
Tarzana, California, United States, 91356
United States, Colorado
Rocky Mountain Clinical Research, LLC
Denver, Colorado, United States, 80229
Colorado Research Works
Pueblo, Colorado, United States, 81008
Rocky Mountain Clinical Research, LLC
Thornton, Colorado, United States, 80229
United States, Connecticut
Connecticut Clinical Research Foundation CT Gastroenterology Institute At Bristol Hospital
Bristol, Connecticut, United States, 06010
United States, District of Columbia
Washington Hospital Center - MedStar Health Research Institute
Washington, District of Columbia, United States, 20010
United States, Florida
Innovative Medical Research of South Florida
Aventura, Florida, United States, 33160
South Lake Pain Institute
Clermont, Florida, United States, 34711
Private Practice
Hollywood, Florida, United States, 33021
Akta Medika
Miami Beach, Florida, United States, 33140
Advance Medical Research Center
Miami, Florida, United States, 33135
Well Pharma Medical Research Corp.
Miami, Florida, United States, 33143
Gastroenterology Group of Naples, PA
Naples, Florida, United States, 34102
Healthcare Clinical Data, Inc.
North Miami, Florida, United States, 33161
Private Practice
Pembroke Pines, Florida, United States, 33024
Advanced Medical Research Center
Port Orange, Florida, United States, 32127
University of South Florida, South Campus
Tampa, Florida, United States, 33606
Florida Medical Clinic, P.A.
Zephyrhills, Florida, United States, 33542
United States, Georgia
Morehouse School of Medicine
Atlanta, Georgia, United States, 30310
Georgia Health Sciences University
Augusta, Georgia, United States, 30912
Atlanta Center for Gastroenterology
Decatur, Georgia, United States, 30033
Gastrointestinal Specialist of Georgia
Marietta, Georgia, United States, 30060
Atlanta Gastroenterology Consultants
Suwanee, Georgia, United States, 30024
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NCH Medical Group
Arlington Heights, Illinois, United States, 60004
North Shore University Health System
Evanston, Illinois, United States, 60201
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
Kendrick Regional Medical Center
Indianapolis, Indiana, United States, 46237
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University of Iowa Hospital and Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202-1622
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Delta Research Partners
Monroe, Louisiana, United States, 71201
New Orleans, Louisiana, United States, 70121
United States, Maryland
Investigative Clinical Research
Annapolis, Maryland, United States, 21401
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Metropolitan Gastroenterology Group, Chevy Chase Clinical Research
Chevy Chase, Maryland, United States, 20815
Gastro Center of Maryland
Columbia, Maryland, United States, 21045
Meritus Center For Clinical Research
Hagerstown, Maryland, United States, 21742
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Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Baystate Medical Center Department of Surgery
Springfield, Massachusetts, United States, 01199
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Center for Digestive Health
Troy, Michigan, United States, 48098
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CRC of Jackson
Jackson, Mississippi, United States, 39202
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Jefferson City Medical Group
Jefferson City, Missouri, United States, 65109
Midwest Center for Clinical Research
Lee's Summit, Missouri, United States, 64064
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Colon and Rectal Surgery, Inc
Omaha, Nebraska, United States, 68114
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Impact Clinical Trials
Las Vegas, Nevada, United States, 89106
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Gastroenterology Group & Endoscopy Center of South NJ (GGSJ)
Vineland, New Jersey, United States, 08360-7072
C&R Surgical Assoc of South Jersey
Voorhees, New Jersey, United States, 08043-9544
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Life Medi-Research and Management
Brooklyn, New York, United States, 11206
HCCA Clinical Research Solutions
New York, New York, United States, 10016
Manhattan Surgical Associates, LLP
New York, New York, United States, 10021
Colorectal Associates of NY
New York, New York, United States, 10022
Medical Research Associates of New York (New York Gastroenterology Associates, LLP)
New York, New York, United States, 10075
Premier Medical Group
Poughkeepsie, New York, United States, 12601
United States, North Carolina
Boone, North Carolina, United States, 28607
Duke University
Durham, North Carolina, United States, 27710
Womack Army Medical Center
Ft. Bragg, North Carolina, United States, 28310-7301
University of North Carolina
Raleigh, North Carolina, United States, 27599
Wake Research Associates
Raleigh, North Carolina, United States, 27612
Trial Management Associates
Wilmington, North Carolina, United States, 28403
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University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Dayton Gastroenterology, Inc.
Dayton, Ohio, United States, 45415
Great Lakes Gastroenterology
Mentor, Ohio, United States, 44060
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Institute of Pain Research
Oklahoma City, Oklahoma, United States, 73104
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Bend Memorial Clinic
Bend, Oregon, United States, 97701
The Corvallis Clinic, Clinical Research Center
Corvallis, Oregon, United States, 97330
Westover Heights Clinic
Portland, Oregon, United States, 97210
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Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
West Penn Allegheny Health System
Monroeville, Pennsylvania, United States, 15146
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19017
Drexel Univ College of Medicine
Philadelphia, Pennsylvania, United States, 19102
Temple University Physicians, Jeanes Hospital
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Pain Specialists of Charleston
North Charleston, South Carolina, United States, 29406
Gastroenterology Associates of Orangeburg, PA
Orangeburg, South Carolina, United States, 29118
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HCCA Clinical Research Solutions
Jackson, Tennessee, United States, 38305
Vanderbilt Univ Dept of Colon and Rectal Surgery
Nashville, Tennessee, United States, 37232
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Research Across America
Dallas, Texas, United States, 75010
Research Concepts, GP LLC
Houston, Texas, United States, 77024
University of TX Affiliated Hospitals
Houston, Texas, United States, 77030
Houston Endoscopy and Research Center
Houston, Texas, United States, 77079
Houston Digestive Disease Clinic
Houston, Texas, United States, 77090-3408
ColoProctology Associates
Seabrook, Texas, United States, 77586
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University of Utah HSC
Salt Lake City, Utah, United States, 84132
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Charlottesville Medical Research
Charlottesville, Virginia, United States, 22911
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Chesapeake, Virginia, United States, 23320
Jefferson Surgical Clinic
Roanoke, Virginia, United States, 24016
United States, Washington
NW Gastroenterology
Bellevue, Washington, United States, 98004
Digestive Disease Institute, Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Madigan Army Medical Center
Tacoma, Washington, United States, 98431
United States, Wisconsin
Medical College of Wisconsin Department of Surgery
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Ventrus Biosciences, Inc

Responsible Party: Ventrus Biosciences, Inc Identifier: NCT01690221     History of Changes
Other Study ID Numbers: VEN307-AF-001
First Posted: September 21, 2012    Key Record Dates
Last Update Posted: January 23, 2014
Last Verified: January 2014

Keywords provided by Ventrus Biosciences, Inc:

Additional relevant MeSH terms:
Fissure in Ano
Anus Diseases
Rectal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents