An Open-Label, Single- and Multi-Dose Pharmacokinetic (PK) Study of Oral Diltiazem and Topical Diltiazem Hydrochloride

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.