The Effect of Intra-anal Nifedipine, Used As Add-on to Conservative Therapy, on Pain in Patients With Anal Fissure

Exclusion Criteria

• •Subjects are excluded from participation in the study if any of the following criteria apply:
• •1. Known allergy to Nifedipine
• •2. Unwilling to stop all other concomitant topical preparations applied in and around the anus from screening through the end of the study
• •3. Subfissure injection of botulinum toxin in the 3 months prior to screening.
• •4. Fissure resulting from inflammatory bowel disease, venereal disease, perianal psoriasis, immunodeficiency syndrome
• •5. Atypical fissure (occurs off the midline) in which secondary causes were not excluded.
• •6. Deemed by the investigator as anal fissure for which surgery is indicated
• •7. Anal abscess;
• •8. Grade 4 hemorrhoids
• •9. Fixed anal stenosis
• •10. Active or past history of cardiovascular or cerebrovascular disease including but not limited to angina pectoris, myocardial infarction, transient ischemic attacks/stroke, arrhythmia or ecg changes that requires medical treatment or deemed by the investigator as clinically significant, moderate to severe congestive heart failure, or cardiac valve abnormalities;
• •11. Type 1 diabetes mellitus
• •12. Insulin treated type 2 diabetes mellitus
• •13. Renal failure defined as a serum creatinine \> 1.5 mg/dL (133 µmol/L) at screening
• •14. Liver disease defined as Aspartate aminotransferase (AST) or alanine aminotransferase(ALT) \>2 X upper limit of normal at screening
• •15. Malignant disease within 3 years of screening
• •16. Has uncontrolled hypertension (sitting blood pressure \>160/95 mmHg at screening)
• •17. Has hypotension (blood pressure lower than 90/60 mm Hg at screening)
• •18. History of chronic gastrointestinal disease such as Crohn's disease or ulcerative colitis
• •19. History of major rectal surgery
• •20. History of HIV, Hepatitis B, Hepatitis C
• •21. Has clinical laboratory test values (chemistry, hematology, or urinalysis) judged to be clinically significant by the investigator at screening;
• •22. 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 Rivaroxaban, Apixaban, Edoxaban
• •23. Is treated with drugs that may affect the anal sphincter:
• •1. Calcium channel blockers such as Nifedipine, Diltiazem or Verapamil
• •2. Nitroglycerin or nitrates
• •24. Has, upon physical examination, a rectal deformation or signs of rectal disease such as fistula, infection or space occupying lesion;
• •25. Participated in a clinical study in the last 30 days prior to screening.
• •26. 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 or related to the Sponsor, CRO or investigator;