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

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

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.

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.