Diltiazem Hydrochloride Cream for Anal Fissure
A Phase III, multicentre, randomised, double blind, placebo-controlled study in subjects having anal fissure (AF) with AF-related pain. Subjects will undertake a 1-week screening period to provide baseline data and for assessment of eligibility. At the Baseline visit (Week 0), eligible subjects (having an average Numerical Rating Scale (NRS) score of >4 for worst pain associated with or following defaecation) will be randomised on a 1:1:1 basis to one of the three treatment groups. Subjects will receive diltiazem hydrochloride 2% cream or diltiazem hydrochloride 4% cream or placebo cream. Study treatment will be applied in and around the anus, three times daily, for up to 8 weeks. Following the Week 0 Visit, subjects will be contacted by telephone during Week 1 to ensure adequate compliance with study treatment, to ensure that study drug is being tolerated and that any concomitant medications are used at a level consistent with that prior to randomisation. Subjects will return to the clinic for safety and efficacy assessments at Weeks 2, 4, and 8 and receive a follow-up telephone call at Week 12, following cessation of therapy.
Concomitant laxatives and stool softeners will be permitted, as needed, during the entire study period (screening and treatment) to ensure that constipation or passage of hard stools does not confound evaluation or improvement of the condition. Fibre supplements will be allowed but should be continued at the baseline level.
Instructions on the use of the Interactive Voice Response System (IVRS) diary will be issued to subjects to record fissure-related pain (NRS) and bowel symptoms daily during the 1-week screening period, to confirm eligibility and post-randomisation to record worst anal pain associated with or following defaecation (NRS) and daily overall AF-related pain (NRS). A record of the number of times the subject has defaecated, laxative and analgesic usage will also be made as well as the number of applications of study treatment, any changes to concurrent medications and any Adverse Events (AEs).
In addition, at some or all study visits, subjects will record the Patient's Global Impression of Improvement (PGI-I) on a 7 point Likert scale, complete a Short Form 36 (SF-36) quality of life questionnaire and will undergo examination of their AF. Routine blood samples will be taken and the Skin Irritation Score (SIS) recorded for safety evaluations.
Subjects may receive permitted medications for pain per Entry Criteria, but these should remain stable, where possible, up to the Week 8 Visit. Introduction of any new medication for AF will not be permitted unless the Investigator deems "rescue" intervention necessary. A subject will be deemed a treatment failure if rescue intervention is required and will have to be withdrawn from the study.
Any subject leaving the study following randomisation for any reason will be asked to complete the Early Withdrawal Visit. This includes subjects who withdraw due to the development of AEs or intolerance, as well as subjects who require rescue intervention. These subjects will return for safety follow-up visits at their previously scheduled follow-up assessment appointments. If complete healing has occurred at the 2 or 4 Week visits, (i.e. prior to the end of the 8-week treatment period), subjects will be asked to continue applying the medication for the full 8 week course, up to the final assessment.
Following the Week 8 visit (or Early Withdrawal Visit), subjects will be followed up for a further 4 weeks (following cessation of study medication) to note any AEs.
All routine blood analyses (haematology and biochemistry) and plasma levels of diltiazem and of its principal metabolites will be analysed by central laboratories.
|Chronic Anal Fissure||Drug: Diltiazem hydrochloride 4% cream Drug: Diltiazem hydrochloride 2% cream Other: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomised,Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Diltiazem Hydrochloride Cream in Subjects With Anal Fissure|
- Change From Baseline in Average of Worst Anal Pain Associated With or Following Defaecation for Week 4 (for the 7 Treatment Days Immediately Preceding the Week 4 Visit). [ Time Frame: 4 weeks ]Change from baseline in average of worst anal pain associated with or following defaecation for Week 4 (for the 7 treatment days immediately preceding the Week 4 visit). Numerical Rating Scale, range 0-10 where 0 = no pain and 10 = worst pain imaginable.
- Patient's Global Impression of Improvement (PGI-I) [ Time Frame: 4 weeks ]Compared to the way you felt prior to starting the study treatment, how would you now describe your problems related to the anal fissure?" Responses will be measured on a 7-point Likert scale where 1 = substantially worse, 2 = moderately worse, 3 = slightly worse, 4 = no change, 5 = slightly improved, 6 = moderately improved, and 7 = substantially improved. Percentage of subjects scoring 5,6 or 7 was assessed.
- Assessment of Adverse Events, Clinical Laboratory Results, Vital Signs and Sensitivity Reactions [ Time Frame: 8 weeks ]Number of subjects with adverse events, abnormal clinical laboratory results, vital signs and occurrence of any local sensitivity reactions. Data are presented where the incidence is greater than or equal to 5%.
|Study Start Date:||October 2010|
|Study Completion Date:||May 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: Diltiazem hydrochloride 4% cream
2.5 cm Diltiazem hydrochloride 4% cream applied peri-anally three times daily for eight weeks.
Drug: Diltiazem hydrochloride 4% cream
3 times daily
Experimental: Diltiazem hydrochloride 2% cream
2.5 cm of Diltiazem hydrochloride 2% cream applied peri-anally three times daily for eight weeks.
Drug: Diltiazem hydrochloride 2% cream
3 times daily
Placebo Comparator: Placebo cream
2.5 cm placebo cream applied peri-anally three times daily for eight weeks.
3 times daily
Please refer to this study by its ClinicalTrials.gov identifier: NCT01217515
|Dr Kantcho Kostadinov|
|Sevileva, Sevilieva, Bulgaria, 5400|
|Sofia, Bulgaria, 1233|
|MHAT Alexandrovska EAD|
|Sofia, Bulgaria, 1606|
|Military Medical Academy|
|Sofia, Bulgaria, 1606|
|Sofia, Bulgaria, 1618|
|General Hospital for Active Treatment "Stefan Cherkezov"|
|Veliko Tarnovo, Bulgaria, 5000|
|Blankenhain, Germany, 99444|
|Fürth, Germany, 90762|
|End- und Dickdarm-Zentrum Mannheim|
|Mannheim, Germany, 68165|
|Marl, Germany, 45770|
|Practice of Internal Medicine|
|Wiesbaden, Germany, 65185|
|Kaunas Medical University Clinics|
|Kaunas, Lithuania, 50009|
|Siauliai, Lithuania, 76231|
|UAB Baltic and American Medical and Surgical Clinic|
|Vilnius, Lithuania, 10103|
|Spitalul Clinic de Urgenta "Prof Dr O Fodor" Cluj|
|Cluj Nopoca, Romania, 400162|
|Spitalul Clinic de Urgenta "Prof. Dr O Fodor"|
|Cluj-Napoca, Romania, 400162|
|Spitalul Judetean de Urgenta Deva|
|Deva, Romania, 330084|
|Institutul de Gastroenterologie si Hepatologie lasi|
|Lasi, Romania, 700111|
|Spitalul Clinic Judetean de Urgente "Sf.Spiridon" lasi|
|Lasi, Romania, 700111|
|Cabinet Medical "Dr Lokos" Chirurgie Generala|
|Miercurea Ciuc, Romania, 530180|
|Spitalul Clinic Judetean Mures|
|Tg Mures, Romania, 540103|
|Centrul Medical Tuculanu SRL|
|Timisoara, Romania, 300167|
|Spitalul Clinic Judetean de Urgenta Timisoara|
|Timisoara, Romania, 300723|
|Zalau, Romania, 450112|
|Hospital Clinico Universitario Lozano Blesa|
|Zaragoza, Spain, 50009|
|Derby City General Hospital|
|Derby, Derbyshire, United Kingdom, DE22 3DT|
|Royal Sussex County Hospital|
|Brighton, United Kingdom, BN2 5BE|
|Study Director:||Chris Jordan, PhD||S.L.A. Pharma|