An Open Label Multi-Dose Study to Examine the Effect of Coated Nifedipine Suppository on Anal Fissure Pain and Healing

This is an open label study. The study will consist of 2 treatment group: coated Nifedipine suppository containing 12 mg of Nifedipine applied twice daily (group 1) and coated Nifedipine suppository containing 12 mg of Nifedipine applied once daily (group 2). Approximately 30 subjects will participate into this 8-week study. The primary objective is to examine the dose effect of coated Nifedipine suppository on Anal fissure pain and healing.

Study Overview

• Status: Terminated
• Conditions: Anal Fissure
• Intervention / Treatment: Drug: Nifedipine 12 mg coated suppositories

Detailed Description

This is an open label study. The study will consist of 2 treatment group: coated Nifedipine suppository containing 12 mg of Nifedipine applied twice daily (group 1) and coated Nifedipine suppository containing 12 mg of Nifedipine applied once daily (group 2). Approximately 30 subjects will participate into this 8-week study. A screening visit will be used to determine subject suitability for inclusion in the trial. Within one week of the screening visit, subjects who meet all inclusion criteria and none of the exclusion criteria will receive Coated Nifedipine 12 mg Suppository X2 a day (BID) (24 mg/day total) OR Coated Nifedipine 12 mg Suppository X1 a day (OD) (12 mg/day total) for a period of 8 weeks. During this period, 4 study visits (at 0, 2, 5, and 8 weeks) will take place. Study medication will be administered BID (in the morning and in the evening) or OD (only in the morning). In addition to receiving study medication, subjects will be maintained on a standard treatment for Anal Fissure: sitz baths, high fiber diet.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Rehovot, Israel
    • Macabi outpatient clinic
  • Tel Aviv, Israel
    • Macabi HMO outpatient clinic
  • Zrifin, Israel
    • Asaf Harofe Hospital
  • Negev
    • Beer Sheba, Negev, Israel
      • Macabi outpatient clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Single anal fissure
• Signed written informed consent;
• Male or female subjects 18 to 65 years of age;
• Has chronic anal fissure defined as history of anal pain at least three days a week for 30 days duration or more
• Visible fibers of the internal sphincter were seen at the base of the fissure or if a sentinel pile was present.
• VAS of > 35 mm in screening visit
• If female, is non-lactating, has a negative urine pregnancy test result, and does not plan on becoming pregnant during the study, or not of childbearing potential (hysterectomy or tubal ligation at least 6 months prior to entry to the study or post-menopausal for 1 year); if of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice or be willing to continue to practice appropriate birth control (such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire study duration.

Exclusion Criteria:

• Known allergy to Nifedipine, polyethylene-glycol, propylene Glycol or silicone.
• Fissure resulting from inflammatory bowel disease, venereal disease, perianal psoriasis, immunodeficiency syndrome.
• Anal abscess
• Fixed anal stenosis
• Active or past history of cardiovascular or cerebrovascular disease including unstable angina, myocardial infarction, transient ischemic attacks/stroke, clinically significant arrhythmia, moderate to severe congestive heart failure, or cardiac valve abnormalities;
• Type 1 diabetes mellitus;
• Insulin treated type 2 diabetes mellitus;
• History of Renal insufficiency.
• History of Liver insufficiency.
• Malignant disease within 5 years of screening;
• Has uncontrolled hypertension (sitting blood pressure <160/95 mmHg at screening)
• History of chronic gastrointestinal disease.
• History of rectal surgery.
• History of gastrointestinal surgery.
• History of HIV, hepatitis B, hepatitis C.
• In need of chronic use of medication, with the exception of birth control medications.
• Currently uses medication for acute illness (other than medications for use of treatment/pain relief of anal fissure).
• Has used, in the last two weeks, drugs that may affect blood coagulation, such as Aspirin at a dose higher than 500 mg/day , Warfarin, Sintrom, Enoxaparin, Nadroparin, Heparin, Clopidogrel, Ticlopidine.
• Is using drug that may affect rectal tone:

• Calcium Channel Blocker such as:

  • Nifedipine (Osmo-Adlat, Pressolat, Nifedipine -Teva, Nifedilong)
  • Amlodipine (Amlow, Norvasc, Amlodipine-Teva)
  • Lercadipine (Vasodip)
  • Verapamil (Ikacor, Ikapress, Verapress)
  • Felodipine (Penedil)
  • Diltiazem (Adizem, Dilatam)

• Nitrate donors such as:

  • Glyceryl Trinitrate (Deponit)
  • Isosorbid dinitrate (Isoket, Isolong)
  • Isosrbid mononitrate (Monocord, Monolong, Mononit)
  • Nitroglycerine (Nitrocine, Nitroderm, Nitrolingual)
• Has upon physical examination a rectal deformation or signs of rectal disease such as bleeding hemorrhoids, fistula. infection or space occupying lesion.
• Is an immediate family member of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site; or
• Is employed by RDD Pharma Ltd.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Once daily; Nifedipine 12 mg Once daily	Drug: Nifedipine 12 mg coated suppositories
Experimental: Twice Daily; Nifedipine 12 mg twice daily	Drug: Nifedipine 12 mg coated suppositories

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To examine the effect of coated Nifedipine suppository on Anal fissure pain as measured by Visual Analog Score	8 weeks after study initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the Safety and tolerability of coated Nifedipine suppositories in Anal Fissure patients .	safety will be assessed by the number of participants with adverse events. Tolerability will be assessed by the number of participants that discontinue treatment.	8 weeks

Collaborators and Investigators

• Sponsor: RDD Pharma Ltd
• Investigators: Study Director: Nir Barak, MD, RDD Pharma Ltd

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 22, 2013
• First Posted (Estimate): December 30, 2013

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: November 15, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Nifedipine; 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; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine
• Other Study ID Numbers: RDD 112