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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Anal Fissures
• Intervention / Treatment: Drug: VEN 307; Drug: Placebo

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
• Enrollment (Actual): 434
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Placebo cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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).	28 days

Collaborators and Investigators

• Sponsor: Ventrus Biosciences, Inc

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: September 17, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Estimate): January 23, 2014
• Last Update Submitted That Met QC Criteria: January 22, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Pain; Anal; Fissure
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Anus Diseases; Fissure in Ano; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Diltiazem
• Other Study ID Numbers: VEN307-AF-001