Clinical trial NCT01690221: Efficacy and Safety Study With Diltiazem Hydrochloride Cream to Treat 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Anal Fissures
Keywords: Anal
Fissure
Pain
Lead sponsor: Ventrus Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2012-09-21
Enrollment: 434
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: 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.

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.

Eligibility 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.

Primary outcomes:
measure: 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).
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: The Crawford Clinic
state: Alabama
city: Mobile
country: United States
facility: Surgical Association of Mobile
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Montgomery
country: United States
facility: Montgomery Women's Health Association, PC
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Tucson
country: United States
facility: Desert Sun Clinical Research, LLC
state: Arizona
city: Colton
country: United States
facility: Arrowhead Regional Medical Center
state: California
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Laguna Hills
country: United States
facility: Alliance Research Centers
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: Los Angeles
country: United States
facility: Gastrointestinal Biosciences
state: California
city: Orange
country: United States
facility: University of California - Irvine Medical Center
state: California
city: San Carlos
country: United States
facility: Digestive Care Associated, A Medical Corporation
state: California
city: Tarzana
country: United States
facility: West Coast Clinical Research
state: California
city: Denver
country: United States
facility: Rocky Mountain Clinical Research, LLC
state: Colorado
city: Pueblo
country: United States
facility: Colorado Research Works
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Clinical Research, LLC
state: Colorado
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation CT Gastroenterology Institute At Bristol Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center - MedStar Health Research Institute
state: District of Columbia
city: Aventura
country: United States
facility: Innovative Medical Research of South Florida
state: Florida
city: Clermont
country: United States
facility: South Lake Pain Institute
state: Florida
city: Hollywood
country: United States
facility: Private Practice
state: Florida
city: Miami Beach
country: United States
facility: Akta Medika
state: Florida
city: Miami
country: United States
facility: Advance Medical Research Center
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research Corp.
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples, PA
state: Florida
city: North Miami
country: United States
facility: Healthcare Clinical Data, Inc.
state: Florida
city: Pembroke Pines
country: United States
facility: Private Practice
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida, South Campus
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic, P.A.
state: Florida
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Augusta
country: United States
facility: Georgia Health Sciences University
state: Georgia
city: Decatur
country: United States
facility: Atlanta Center for Gastroenterology
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialist of Georgia
state: Georgia
city: Suwanee
country: United States
facility: Atlanta Gastroenterology Consultants
state: Georgia
city: Arlington Heights
country: United States
facility: NCH Medical Group
state: Illinois
city: Evanston
country: United States
facility: North Shore University Health System
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Indianapolis
country: United States
facility: Kendrick Regional Medical Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Monroe
country: United States
facility: Delta Research Partners
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner
state: Louisiana
city: Annapolis
country: United States
facility: Investigative Clinical Research
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group, Chevy Chase Clinical Research
state: Maryland
city: Columbia
country: United States
facility: Gastro Center of Maryland
state: Maryland
city: Hagerstown
country: United States
facility: Meritus Center For Clinical Research
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center Department of Surgery
state: Massachusetts
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Jackson
country: United States
facility: CRC of Jackson
state: Mississippi
city: Jefferson City
country: United States
facility: Jefferson City Medical Group
state: Missouri
city: Lee's Summit
country: United States
facility: Midwest Center for Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Colon and Rectal Surgery, Inc
state: Nebraska
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Vineland
country: United States
facility: Gastroenterology Group & Endoscopy Center of South NJ (GGSJ)
state: New Jersey
city: Voorhees
country: United States
facility: C&R Surgical Assoc of South Jersey
state: New Jersey
city: Brooklyn
country: United States
facility: Life Medi-Research and Management
state: New York
city: New York
country: United States
facility: HCCA Clinical Research Solutions
state: New York
city: New York
country: United States
facility: Manhattan Surgical Associates, LLP
state: New York
city: New York
country: United States
facility: Colorectal Associates of NY
state: New York
city: New York
country: United States
facility: Medical Research Associates of New York (New York Gastroenterology Associates, LLP)
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group
state: New York
city: Boone
country: United States
facility: Medispect
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Ft. Bragg
country: United States
facility: Womack Army Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: University of North Carolina
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dayton
country: United States
facility: Dayton Gastroenterology, Inc.
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology
state: Ohio
city: Oklahoma City
country: United States
facility: Institute of Pain Research
state: Oklahoma
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Corvallis
country: United States
facility: The Corvallis Clinic, Clinical Research Center
state: Oregon
city: Portland
country: United States
facility: Westover Heights Clinic
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Monroeville
country: United States
facility: West Penn Allegheny Health System
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel Univ College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Physicians, Jeanes Hospital
state: Pennsylvania
city: North Charleston
country: United States
facility: Pain Specialists of Charleston
state: South Carolina
city: Orangeburg
country: United States
facility: Gastroenterology Associates of Orangeburg, PA
state: South Carolina
city: Jackson
country: United States
facility: HCCA Clinical Research Solutions
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univ Dept of Colon and Rectal Surgery
state: Tennessee
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: Houston
country: United States
facility: Research Concepts, GP LLC
state: Texas
city: Houston
country: United States
facility: University of TX Affiliated Hospitals
state: Texas
city: Houston
country: United States
facility: Houston Endoscopy and Research Center
state: Texas
city: Houston
country: United States
facility: Houston Digestive Disease Clinic
state: Texas
city: Seabrook
country: United States
facility: ColoProctology Associates
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah HSC
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Roanoke
country: United States
facility: Jefferson Surgical Clinic
state: Virginia
city: Bellevue
country: United States
facility: NW Gastroenterology
state: Washington
city: Seattle
country: United States
facility: Digestive Disease Institute, Virginia Mason Medical Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Department of Surgery
state: Wisconsin
Study officials:
References: