Study to Evaluate the Interaction Potential of Clarithromycin XL on Diltiazem Hydrochloride Cream 2% in Healthy Subjects
Condition: CLARITHROMYCIN/DILTIAZEM [VA Drug Interaction]
Intervention: Clarithromycin XL; 2% Diltiazem
Intervention description: Clarithromycin XL administered once daily on Days 4 through 9 as 2 x 500 mg tablets, 1000 mg per day, for a total of 6000 mg; 2% Diltiazem Hydrochloride Cream applied on Day 1 & Day 8 to the perianal area (~2.5 cm [1 inch]; ~8.5 mg)
Intervention MeSH terms: Clarithromycin; Diltiazem
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the drug-drug interaction potential of
      clarithromycin XL on Diltiazem hydrochloride (DTZ) 2% cream.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Were healthy subjects (as confirmed by medical history, laboratory work, and physical
             exam);

          2. Were between 18 and 60 years of age, inclusive;

          3. If of childbearing potential, were using an acceptable form of birth control (ie,
             nonhormonal intra-uterine device, diaphragm, condom, bilateral tubal ligation,
             abstinence, or were in a monogamous relationship with a partner who had a vasectomy);

          4. In the case of females of childbearing potential, had a negative serum pregnancy test
             (SPT) at Screening and a negative urine pregnancy test (UPT) at Study Day -1, (a woman
             was considered to be of childbearing potential unless she was postmenopausal for at
             least 12 months or was surgically sterile [hysterectomy, bilateral oophorectomy]);

          5. Had clinical lab tests (hematology, chemistry, and urinalysis), an electrocardiogram
             (ECG), and vital signs within normal limits, or assessed by the investigator as not of
             clinical significance; and

          6. Were able to read, understand, and provide signed informed consent.

        Exclusion Criteria:

          1. On any drug treatment at the time of the study;

          2. Had donated plasma (500 mL) within 7 days prior to drug administration;

          3. Had donated or lost whole blood (excluding the volume of blood that was to be drawn
             during the screening procedures of this study) prior to administration of the study
             medication as follows: 50 mL to 499 mL of whole blood within 30 days, or more than 499
             mL of whole blood within 56 days prior to drug administration;

          4. Were using and were unwilling to stop any other concomitant topical preparations in or
             around the anus and perianal area from Day -1 through the end of the study;

          5. Had a hypersensitivity or allergy to the investigational compound/compound class used
             in this study, and bacterial fighting medications, including but not limited to
             clarithromycin XL , azithromycin, telithromycin, and erythromycin or to calcium
             channel blockers;

          6. Had a history or presence of neurological, endocrinal, cardiovascular, pulmonary,
             hematologic, immunologic, psychiatric, or metabolic disease, that, in the opinion of
             the investigator, could have interfered with the study conduct or observation;

          7. Were unable to adhere to or understand the requirements of the protocol;

          8. Had a body mass index > 40 kg/m2;

          9. Had a screening ECG >470 QTCF for females and >450 QTCF for males;

         10. Were on active treatment with anti-viral therapies (eg, indinavir, nelfinavir,
             ritonavir) for human immunodeficiency virus (HIV);

         11. Had been treated with any of the following medications within 14 days prior to signing
             the ICF:

               -  CYP450 inhibitors and inducers;

               -  CYP3A4 substrates, inhibitors, and inducers;

               -  Benzodiazepines;

               -  β-adrenoceptor antagonists (beta-blockers);

               -  Calcium channel blockers;

               -  Digoxin;

               -  Investigational agents;

               -  Opioids.

         12. Had any of the following concomitant disease states:

               -  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 (< 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 (eg, Crohn's disease, ulcerative colitis);

               -  History of any prior anal or rectal surgery including but not limited to: lateral
                  sphincterotomy and anal stretch;

         13. Had a major organ transplant;

         14. Had a serious illness in the 4 weeks preceding the beginning of treatment (ie, that
             resulted in missed work or hospitalization);

         15. Had received treatment for any type of internal cancer within the 5 years prior to
             enrollment;

         16. Had, in the opinion of the investigator, clinically significant abnormal clinical
             laboratory results at the time of screening;

         17. Were females who were pregnant, were planning to become pregnant during the study, or
             were breastfeeding a child;

         18. Were currently using narcotics chronically;

         19. Were currently a smoker;

         20. Had used an investigational drug or had participated in an investigational study
             within 30 days prior to dosing;

         21. Had used prescription medication within 14 days prior to administration of study
             medication or over-the-counter (OTC) products (including natural food supplements
             vitamins, garlic as a supplement) within 7 days prior to administration of study
             medication, except for topical products without systemic absorption;

         22. Were an employee, family member, or student of the investigator or clinical site;

         23. Had any food allergy, intolerance, restriction, or special diet that, in the opinion
             of the investigator, could have contraindicated the subject's participation in this
             study.