A Randomised, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Diltiazem Hydrochloride Cream in Subjects with Anal Fissure - Diltiazem hydrochloride cream for anal fissure.
- Conditions
- Symptomatic relief of pain related to anal fissure (AF).MedDRA version: 12.1Level: LLTClassification code 10002153Term: Anal fissure
- Registration Number
- EUCTR2008-005172-26-LT
- Lead Sponsor
- S.L.A. Pharma (UK) Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 465
- Must give written informed consent.
- Male or female subjects = 18 years of age.
- Subjects with at least a 4 week history of painful AF prior to screening, where
AF-related pain associated with, or following, defaecation is experienced at least
twice a week for the 4 weeks prior to screening with an average of = 3 on an
11-point NRS.
- Subjects with an average of =4, on an 11-point NRS, during the screening phase, for
worst anal pain associated with, or following, defaecation for the most recent three
days on which the subject has defaecated.
- Subjects with evidence of a circumscribed fissure, with induration at the edges.
- Willing to stop all other concomitant topical preparations applied perianally prior to
commencing study treatment and throughout the study.
- Willingness and ability to use the IVRS diary.
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
- Subjects unwilling to have examination of AF.
- Subjects with acute” AF (i.e. duration of symptoms less than 4 weeks prior to
screening, and/or no induration of fissure edges).
- More than one AF.
- Subjects who have had lateral sphincterotomy or anal stretch or other previous
surgery involving the anal canal or perianal region.
- Subjects who have had subfissure injection of botulinum toxin in the 3 months prior
to screening, or have used GTN ointment for >1 week in the 4 weeks prior to the
screening visit.
- Subjects with AF associated with other conditions (drug-induced [e.g. nicorandil],
trauma, HIV infection, fistula-in-ano, inflammatory bowel disease, perianal sepsis or
malignancy).
- Subjects with cardiovascular disease (including those diagnosed by screening ECG):
history of reduced left ventricular function, bradycardia, 1st degree AV block or
prolonged PR interval (>0.2 seconds/ >200 milliseconds).
- Subjects with known hypersensitivity to diltiazem.
- Subjects who have previously received therapy with diltiazem hydrochloride cream or
other topical calcium channel blockers.
- Subjects taking prohibited medications.
- Subjects who have taken experimental agents must have been discontinued at least
8 weeks prior to screening, or for a period equivalent to 5 half-lives (t1/2) of the
agent (whichever is longer);
- Subjects who have or who have undergone the following gastrointestinal disorders
and procedures:-
- Inflammatory bowel disease.
- Chronic faecal incontinence.
- History of chronic constipation or constipation in the 4 weeks prior to the
screening phase (defined as 2 or less defaecations per week; associated with
straining/passage of hard stools).
- Anal abscess.
- A history of radiation therapy to the pelvis.
- Fixed anal stenosis/fibrosis.
- Subjects with a history of neoplastic disease within 5 years (except for basal cell
carcinoma or non-metastatic squamous cell carcinoma of the skin).
- Subjects with a clinically significant history of renal, hepatic, neurological,
dermatological, immunological, major psychiatric (including drug or alcohol abusers),
or haematological illness.
- Subjects with any laboratory test/ECG results considered clinically significant at
screening.
- Subjects with planned elective or other treatment requiring hospitalisation, during
the study, booked before entry into the study
- Subjects who will be unavailable for the duration of the trial, likely to be
noncompliant with the protocol, or who are felt to be unsuitable by the Investigator
for any other reason.
- Women of childbearing potential unless surgically sterile or using adequate
contraception (either intrauterine device [IUD], oral or depot contraceptive, or barrier
plus spermicide), and willing and able to continue contraception for 1 month after the
last application of study drug. Women using oral contraception must have started
using it at least 2 months prior to enrolment.
- Women who are pregnant or breastfeeding.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of diltiazem hydrochloride cream in reducing pain associated with AF.;Secondary Objective: - To determine the effect of diltiazem hydrochloride cream on subjects' overall <br> improvement of condition.<br>- To determine the effect of diltiazem hydrochloride cream on quality of life.<br>- To determine the optimum dosage of diltiazem hydrochloride cream.<br>- To determine the time course of any effects of diltiazem hydrochloride cream in <br> reducing pain.<br>- To determine the effect of diltiazem hydrochloride cream on healing of AF.<br>;Primary end point(s): Using a NRS for assessment of pain associated with AF:<br>- Change from baseline in average of worst anal pain associated with, or following, <br> defaecation for Week 4 (for the 7 treatment days immediately preceding the Week 4 <br> visit).<br><br>Note: An average score will be calculated for all days when subject has defaecated for Week 4.
- Secondary Outcome Measures
Name Time Method