Clinical Trial: Diltiazem Hydrochloride Cream for Anal Fissure

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomised,Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Diltiazem Hydrochloride Cream in Subjects With Anal Fissure

Brief Summary:

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

Detailed Summary:
Sponsor: S.L.A. Pharma AG

Current Primary Outcome: 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 ]

Original Primary Outcome: 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 ]

Current Secondary Outcome:

• 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%.

Original Secondary Outcome:

• PGI-I [ Time Frame: 4 weeks ]
• Proportion (%) of subjects achieving an average of >30% reduction from baseline in the NRS for 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 ]
• Proportion (%) of subjects achieving an average >30% reduction on the NRS, for overall daily AF-related pain, 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 each week, excluding week 4, (for the 7 treatment days immediately preceding that Week). [ Time Frame: 4 weeks ]
• Change from baseline in average of daily overall AF-related pain for each week (for the 7 treatment days immediately preceding that Week). [ Time Frame: Each week ]
• Responder analysis curve: worst anal pain associated with/or following defecation. [ Time Frame: 4 weeks ]
• Responder analysis curve: overall daily AF-related pain [ Time Frame: 4 weeks ]
• Time to response, defined as >30% reduction from baseline on the NRS, for worst anal pain associated with or following defaecation. Time is defined as a Week with the response taken from the 7 treatment days immediately preceding that week. [ Time Frame: Each week ]
• Time to response, defined as a >30% reduction from baseline on the NRS, for daily overall AF-related pain. Time is defined as a Week with the response taken from the 7 treatment days immediately preceding that week. [ Time Frame: Each week ]
• Mean change in SF-36 - QOL at Week 4. [ Time Frame: 4 weeks ]
• Proportion of subjects who have complete healing of AF (defined as complete epithelialisation of fissure) by Week 8. [ Time Frame: 8 weeks ]
• Assessemtn of adverse events, clinical laboratory results, vital signs and sensitivity reactions [ Time Frame: 12 weeks ]
  Number of subjects with adverse events, frequency of events, abnormal clinical laboratory results, vital signs and occurrence of any local sensitivity reactions

Dates:
Date Received: October 6, 2010
Date Started: October 2010
Date Completion:
Last Updated: July 7, 2014
Last Verified: July 2014