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

Condition(s) targeted: Chronic Anal Fissures

Intervention: VEN 307 (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Ventrus Biosciences, Inc

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: 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).

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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.

The Crawford Clinic, Anniston, Alabama 36207, United States

Surgical Association of Mobile, Mobile, Alabama 36607, United States

University of South Alabama, Mobile, Alabama 36617, United States

Montgomery Women's Health Association, PC, Montgomery, Alabama 36117, United States

Mayo Clinic - Arizona, Phoenix, Arizona 85054, United States

Desert Sun Clinical Research, LLC, Tucson, Arizona 85710, United States

Arrowhead Regional Medical Center, Colton, California 92324, United States

UC San Diego, La Jolla, California 92093, United States

Alliance Research Centers, Laguna Hills, California 92653, United States

Axis Clinical Trials, Los Angeles, California 90036, United States

Cedars Sinai, Los Angeles, California 90048, United States

Gastrointestinal Biosciences, Los Angeles, California 90067, United States

University of California - Irvine Medical Center, Orange, California 92868, United States

Digestive Care Associated, A Medical Corporation, San Carlos, California 94070, United States

West Coast Clinical Research, Tarzana, California 91356, United States

Rocky Mountain Clinical Research, LLC, Denver, Colorado 80229, United States

Colorado Research Works, Pueblo, Colorado 81008, United States

Rocky Mountain Clinical Research, LLC, Thornton, Colorado 80229, United States

Connecticut Clinical Research Foundation CT Gastroenterology Institute At Bristol Hospital, Bristol, Connecticut 06010, United States

Washington Hospital Center - MedStar Health Research Institute, Washington, District of Columbia 20010, United States

Innovative Medical Research of South Florida, Aventura, Florida 33160, United States

South Lake Pain Institute, Clermont, Florida 34711, United States

Private Practice, Hollywood, Florida 33021, United States

Akta Medika, Miami Beach, Florida 33140, United States

Advance Medical Research Center, Miami, Florida 33135, United States

Well Pharma Medical Research Corp., Miami, Florida 33143, United States

Gastroenterology Group of Naples, PA, Naples, Florida 34102, United States

Healthcare Clinical Data, Inc., North Miami, Florida 33161, United States

Private Practice, Pembroke Pines, Florida 33024, United States

Advanced Medical Research Center, Port Orange, Florida 32127, United States

University of South Florida, South Campus, Tampa, Florida 33606, United States

Florida Medical Clinic, P.A., Zephyrhills, Florida 33542, United States

Morehouse School of Medicine, Atlanta, Georgia 30310, United States

Georgia Health Sciences University, Augusta, Georgia 30912, United States

Atlanta Center for Gastroenterology, Decatur, Georgia 30033, United States

Gastrointestinal Specialist of Georgia, Marietta, Georgia 30060, United States

Atlanta Gastroenterology Consultants, Suwanee, Georgia 30024, United States

NCH Medical Group, Arlington Heights, Illinois 60004, United States

North Shore University Health System, Evanston, Illinois 60201, United States

Indiana University School of Medicine, Indianapolis, Indiana 46202, United States

Kendrick Regional Medical Center, Indianapolis, Indiana 46237, United States

University of Iowa Hospital and Clinics, Iowa City, Iowa 52242, United States

University of Louisville, Louisville, Kentucky 40202-1622, United States

Delta Research Partners, Monroe, Louisiana 71201, United States

Ochsner, New Orleans, Louisiana 70121, United States

Investigative Clinical Research, Annapolis, Maryland 21401, United States

University of Maryland Medical Center, Baltimore, Maryland 21201, United States

Metropolitan Gastroenterology Group, Chevy Chase Clinical Research, Chevy Chase, Maryland 20815, United States

Gastro Center of Maryland, Columbia, Maryland 21045, United States

Meritus Center For Clinical Research, Hagerstown, Maryland 21742, United States

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States

Baystate Medical Center Department of Surgery, Springfield, Massachusetts 01199, United States

Center for Digestive Health, Troy, Michigan 48098, United States

CRC of Jackson, Jackson, Mississippi 39202, United States

Jefferson City Medical Group, Jefferson City, Missouri 65109, United States

Midwest Center for Clinical Research, Lee's Summit, Missouri 64064, United States

Colon and Rectal Surgery, Inc, Omaha, Nebraska 68114, United States

Impact Clinical Trials, Las Vegas, Nevada 89106, United States

Gastroenterology Group & Endoscopy Center of South NJ (GGSJ), Vineland, New Jersey 08360-7072, United States

C&R Surgical Assoc of South Jersey, Voorhees, New Jersey 08043-9544, United States

Life Medi-Research and Management, Brooklyn, New York 11206, United States

Colorectal Associates of NY, New York, New York 10022, United States

HCCA Clinical Research Solutions, New York, New York 10016, United States

Manhattan Surgical Associates, LLP, New York, New York 10021, United States

Medical Research Associates of New York (New York Gastroenterology Associates, LLP), New York, New York 10075, United States

Premier Medical Group, Poughkeepsie, New York 12601, United States

Medispect, Boone, North Carolina 28607, United States

Duke University, Durham, North Carolina 27710, United States

Womack Army Medical Center, Ft. Bragg, North Carolina 28310-7301, United States

University of North Carolina, Raleigh, North Carolina 27599, United States

Wake Research Associates, Raleigh, North Carolina 27612, United States

Trial Management Associates, Wilmington, North Carolina 28403, United States

Cleveland Clinic, Cleveland, Ohio 44195, United States

University Hospitals Case Medical Center, Cleveland, Ohio 44106, United States

Dayton Gastroenterology, Inc., Dayton, Ohio 45415, United States

Great Lakes Gastroenterology, Mentor, Ohio 44060, United States

Institute of Pain Research, Oklahoma City, Oklahoma 73104, United States

Bend Memorial Clinic, Bend, Oregon 97701, United States

The Corvallis Clinic, Clinical Research Center, Corvallis, Oregon 97330, United States

Westover Heights Clinic, Portland, Oregon 97210, United States

Penn State Hershey Medical Center, Hershey, Pennsylvania 17033, United States

West Penn Allegheny Health System, Monroeville, Pennsylvania 15146, United States

Drexel Univ College of Medicine, Philadelphia, Pennsylvania 19102, United States

Temple University Physicians, Jeanes Hospital, Philadelphia, Pennsylvania 19111, United States

Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19017, United States

Pain Specialists of Charleston, North Charleston, South Carolina 29406, United States

Gastroenterology Associates of Orangeburg, PA, Orangeburg, South Carolina 29118, United States

HCCA Clinical Research Solutions, Jackson, Tennessee 38305, United States

Vanderbilt Univ Dept of Colon and Rectal Surgery, Nashville, Tennessee 37232, United States

Research Across America, Dallas, Texas 75010, United States

Houston Digestive Disease Clinic, Houston, Texas 77090-3408, United States

Houston Endoscopy and Research Center, Houston, Texas 77079, United States

Research Concepts, GP LLC, Houston, Texas 77024, United States

University of TX Affiliated Hospitals, Houston, Texas 77030, United States

ColoProctology Associates, Seabrook, Texas 77586, United States

University of Utah HSC, Salt Lake City, Utah 84132, United States

Charlottesville Medical Research, Charlottesville, Virginia 22911, United States

Gastroenterology Associates of Tidewater, Chesapeake, Virginia 23320, United States

Jefferson Surgical Clinic, Roanoke, Virginia 24016, United States

NW Gastroenterology, Bellevue, Washington 98004, United States

Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington 98101, United States

Madigan Army Medical Center, Tacoma, Washington 98431, United States

Medical College of Wisconsin Department of Surgery, Milwaukee, Wisconsin 53226, United States

Starting date: October 2012
Last updated: January 22, 2014