Clinical trial NCT01816191: An Open-Label, Single- and Multi-Dose Pharmacokinetic (PK) Study of Oral Diltiazem and Topical Diltiazem Hydrochloride
Official title: An Open-Label, Single- and Multi-Dose Pharmacokinetic (PK) Study of Oral Diltiazem and Topical Diltiazem Hydrochloride
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Adult Subjects With Anal Fissures.
Lead sponsor: Ventrus Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2013-03-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Single and multiple dose Pharmacokinetic parameters
timeFrame: up to 6 months after enrollment begins
Secondary outcomes:
measure: Safety as determined by nature, severity and relationship of adverse events, clinical labs, physical exam findings, vital signs and Electrocardiogram
timeFrame: Up to 6 months after enrollment begins
Other outcomes:
Locations:
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
Study officials:
References: