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.
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
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.