an open-label, single- and multi-dose pharmacokinetic (pk) study of oral diltiazem and topical diltiazem hydrochloride

Conditions: Adult Subjects With Anal Fissures.

Summary: the study is a single-center, open-label, safety and pharmacokinetic study in12 adult subjects with anal fissures. subjects will be screened to determine eligibility within 7 days of treatment. there will be three parts to the study and all subjects will participate in each part.


Eligibility criteria:
inclusion criteria: * subjects with evidence of a circumscribed anal fissure, with induration at the edges. * any female of non-childbearing potential who: a) has had a hysterectomy, b) has had a bilateral oophorectomy, c) has had a bilateral tubal ligation or d) is post-menopausal (demonstration of total cessation of menses for ≥ 1 year from the date of the screening visit). * any female of child bearing potential must agree to use at least one form of contraception(may be a barrier method), during the full duration of the study. * able to communicate adequately with the investigator and to comply with the requirements for the entire study. * capable of and freely willing to provide written informed consent prior to participating in the study. exclusion criteria: * unwilling to have visual or medical examination of the anal fissure. * more than 1 anal fissure. * subjects with anal fissure associated with or caused by other conditions, including but not limited to: drug-induced, trauma, hiv infection, fistula-in-ano, inflammatory bowel disease, perianal sepsis or malignancy. * unwilling to stop all other concomitant topical preparations applied in and around the anus from day -1 through end of the study. * use of sitz bath from signing of icf (informed consent form) to end of study. * use of anesthetics from signing the icf to end of study. * subfissure injection of botulinum toxin in the 3 months prior to signing the icf. * known sensitivity to investigational product(s) or calcium channel blockers. * active treatment with anti-viral therapies for hiv (e.g. indinavir, nelfinivir,ritonavir). 10. treatment with any prohibited medications within 14 days prior to signing the icf: * cytochrome p450 (cyp450) inhibitors and inducers * cytochrome p3a4 (cyp3a4) substrates, inhibitors, and inducers * benzodiazepines * β-adrenoceptor antagonists (beta-blockers) * calcium channel blockers * digoxin * investigational agents * opioids * following concomitant disease state: * sick sinus syndrome except in the presence of a functioning ventricular pacemaker. * second-or third-degree atrioventricular block except in the presence of a functioning ventricular pacemaker. * hypotension (less than 90 mm hg systolic). * acute myocardial infarction and pulmonary congestion documented by x-ray. * history of clinically significant renal disease. * history of clinically significant alzheimer's or parkinson's disease. * history of clinically significant hepatic disease. * current infection treated with a macrolide antibiotic. * clinical evidence or history of fecal incontinence. * clinical evidence or history of anal fistula. * clinical evidence or history of anal abscess. * history of inflammatory bowel disease (e.g. crohn's disease, ulcerative colitis). * history of any prior anal or rectal surgery including but not limited to: lateral sphincterotomy and anal stretch. * history of radiation therapy to the pelvis. * fixed anal stenosis/fibrosis. * major organ transplant. * any clinically significant laboratory abnormalities during screening. * bmi \> 40 kg/m2. * malignancy within 5 years prior to randomization (with the exception of treated basal cell/squamous cell carcinoma of the skin). * any disease or prior/planned surgery that may interfere with the subject successfully completing the study. * currently using narcotic(s) chronically. * breast-feeding females. * employees, family members, or students of the investigator or clinical site.