Chronic anal fissure MedDRA version: 8.1 Level: LLT Classification code 10002153 Term: Anal fissure
Conditions
Interventions
Product Name: Diltiazem hydrochloride cream
Pharmaceutical Form: Cream
CAS Number: 33286225
Other descriptive name: DILTIAZEM HYDROCHLORIDE
Concentration unit: % (W/W) percent weight/weight
Concentrat
Sponsors
S.L.A. Pharma (UK) Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study, subjects must satisfy all of the following criteria: 1. Male or female subjects aged = 18 years who have given written, informed consent. 2. Symptomatic, chronic anal fissure (pain on or following defecation) present for =4 weeks and presenting with notable fissure-related pain. 3. Evidence of circumscribed fissure, with induration at the edges, with or without a sentinel tag. 4. Female subjects of childbearing potential must have negative urine pregnancy test on entry and be using adequate contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects for whom any of the following criteria apply are not eligible for inclusion in the study: 1. Subject with acute fissure (symptoms of duration <4 weeks, no induration at edges). 2. Previous surgical treatment for anal fissure. 3. Other previous surgery involving the anal canal or perianal region. 4. Score of =30mm at baseline on the Visual Analogue Scale (VAS) for anal pain on defecation and a score of =2 on the Numeric Rating Scale for anal pain on defecation (baseline pain score is the average anal pain on defecation for the 3 defecations prior to randomisation). 5. Medical treatment of anal fissure during the past 4 weeks with gyceryl trinitrate cream (GTN cream, Rectogesic) or topical steroid containing creams (e.g. Xyloproct cream, Anusol HC etc.). 6. Subjects who have previously failed to respond to topical diltiazem therapy. 7. Subjects currently using any drugs which, in the opinion of the investigator, may influence anal sphincter tone or blood supply (e.g. a- or ß-adrenoceptor agonists [other than inhaled ß-agonists] or antagonists, sympathomimetics, anti-hypertensive agents, medical treatments for irritable bowel syndrome, PDE V inhibitors). 8. Subjects on antibiotic therapy. 9. Subjects with a history of inflammatory bowel disease. 10. Subjects with anal fissure associated with other conditions such as HIV infection, fistula-in-ano, perianal sepsis, malignancy or as a result of traumatic childbirth. 11. History or evidence on examination of pre-existing cardiac disease, including severe bradycardia, arrhythmias and conduction abnormalities. 12. Coexisting gastrointestinal disease or previous gut resection. 13. Known hypersensitivity to diltiazem. 14. Any mental or other impairment which, in the investigator’s opinion would render them unlikely to be able to comply with the requirements of the study. 15. Participation in a clinical trial within the past 3 months. 16. Previous participation in the D-CAF-06 trial. 17. Concomitant medication acting on the central nervous, cardiovascular (other than low-dose aspirin for prophylaxis) or gastrointestinal system. Xyloproct use is not permitted. Analgesics use is also not permitted during the study, although limited paracetamol use will be permitted. 18. Women who are pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether topical application of diltiazem cream is superior to placebo in relieving pain associated with anal fissure. ;Secondary Objective: 1. To determine the optimum concentration of diltiazem cream, applied topically, to provide relief from pain associated with chronic anal fissure. 2. To determine the impact of topical diltiazem on the healing of chronic anal fissure. 3. To evaluate the safety and tolerability of topical diltiazem cream in the treatment of chronic anal fissure. 4. To evaluate the population kinetics after topical administration of diltiazem cream. 5. To determine the impact of topical diltiazem on Quality of Life in patients with chronic anal fissure. ;Primary end point(s): Efficacy will be based on pain on defecation experienced each day and will be recorded on a visual analogue scale (VAS) pain score (0-100mm) in the subject diary. The primary measure of efficacy will be response to treatment assessed as the percentage change in the Week 4 average pain on defecation score compared to baseline i.e. [Sum of pain on defecation, for each defecation, from Day 22 to Day 28 inclusive] divided by [Number of defecations] Response is defined as a = 30% decrease in Week 4 average pain score from baseline. The average pain on defecation will be calculated for each treatment week; Week 4 will be considered primary. Baseline pain score will be average pain on defecation for the 3 defecations prior to randomisation. | — |
Countries
United Kingdom
Outcome results
None listed