Drug Interaction With Proton Pump Inhibitors for Nifedipine ER Tablets
Condition: Healthy Volunteers
Intervention: Nifedipine 60 MG Extended Release Oral Tablet; Nifedipine 60 MG Extended Release Oral Tablet; omeprazole/sodium bicarbonate; SmartPill (TM)
Intervention description: Reference Drug (Brand); Test Drug (Generic); Proton Pump Inhibitor/Antacid for drug-drug interaction; Gastric pH measurement using SmartPill (TM) Technology
Intervention MeSH terms: Nifedipine; Omeprazole; Omeprazole, sodium bicarbonate drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: A single-dose, randomized, open-label, drug-drug interaction (DDI), 4-way crossover, four-treatment, four-sequence, bioequivalence study
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Proton Pump Inhibitor; Bioequivalence; Drug-Drug Interaction; Modified Release; Nifedipine

Summary:

      The purpose of this study is to measure the amount of study drug present in blood after being
      administered a generic version of nifedipine extended-release tablets, 60 mg (Valeant
      Pharmaceuticals, LLC) and brand-name version PROCARDIA XL extended-release tablets, 60 mg
      (Pfizer Inc.) individually and in presence of stomach acid reducing drug (antacid),
      omeprazole/sodium bicarbonate capsules, 40 mg/1100 mg (generic) on separate occasions, on an
      empty stomach. This study also involves administrations of an FDA-cleared capsule,
      SmartPill™, which will measure stomach acid, prior to each study arm.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy, males and non-pregnant female volunteers, 18 to 55 years of age, inclusive.

          2. Smoking status: Only non-tobacco/nicotine users (for at least 6 months prior to the
             clinical study) will be eligible to participate in this study.

          3. BMI that is within 18.5-35.0 kg/m², inclusive.

          4. Healthy, according to the medical history, ECG, vital signs, laboratory results and
             physical examination as determined by the PI/Sub-Investigator.

          5. Ability to comprehend and be informed of the nature of the study, as assessed by BPSI
             staff. Capable of giving written informed consent prior to receiving any study
             procedure. Must be able to communicate effectively with clinic staff.

          6. Ability to fast for at least 14 hours.

          7. Availability to volunteer for the entire study duration and willing to adhere to all
             protocol requirements.

          8. Female subjects must fulfill at least one of the following:

               -  Be surgically sterile for a minimum of 6 months;

               -  Post-menopausal for a minimum of 1 year;

               -  Agree to avoid pregnancy and use medically acceptable method of contraception
                  from at least 30 days prior to the study until 30 days after the study has ended
                  (last study procedure).

        Medically acceptable methods of contraception include non-hormonal contraceptives,
        intrauterine device, or double barrier method (condom with foam or vaginal spermicidal
        suppository, diaphragm with spermicide). Complete abstinence alone can be used as a method
        of contraception.

        Exclusion Criteria:

          1. Known history or presence of any clinically significant hepatic, renal/genitourinary,
             gastrointestinal (e.g., gastrointestinal obstruction, gastrointestinal ulcers),
             cardiovascular (e.g., severe obstructive coronary artery disease, myocardial
             infarction, angina, heart failure), cerebrovascular, pulmonary, endocrine,
             immunological, musculoskeletal, neurological, psychiatric, dermatological or
             hematological disease or condition unless determined as not clinically significant by
             the PI/Sub-Investigator.

          2. Clinically significant history or presence of any clinically significant
             gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel disease),
             unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting, swallowing disorder),
             or other conditions known to interfere with the absorption, distribution, metabolism
             or excretion of the drug experienced within 7 days prior to first dosing, as
             determined by the PI/Sub-Investigator.

          3. QTc interval > 430 milliseconds for males and > 450 milliseconds for females, unless
             deemed otherwise by the PI/Sub-Investigator.

          4. Abnormal clinical laboratory values, unless values are deemed by the
             PI/Sub-Investigator as "Not Clinically Significant".

          5. Hemoglobin values less than 11.5 g/dl.

          6. Abnormal vital signs (blood pressure [BP], heart rate [HR], respiratory rate [RR] and
             temperature) measurements, unless deemed otherwise by the PI/Sub-Investigator.

          7. Presence of any clinically significant illness within 30 days prior to first dosing,
             as determined by the PI/Sub-Investigator.

          8. Presence of any significant physical or organ abnormality as determined by the
             PI/Sub-Investigator.

          9. Individuals who have implanted or portable electro-mechanical medical device such as a
             cardiac pacemaker, defibrillator or infusion pump.

         10. A positive test result for any of the following: HIV, Hepatitis B surface antigen,
             Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates,
             phencyclidine and benzodiazepines), alcohol test and cotinine. Positive pregnancy test
             for female subjects.

         11. Known history or presence of:

               -  Alcohol abuse or dependence within one year prior to first study period;

               -  Drug abuse or dependence;

               -  Hypersensitivity or idiosyncratic reaction to nifedipine, omeprazole/sodium
                  bicarbonate, its excipients, and/or related substances;

               -  Hypotension;

               -  Bartter's syndrome;

               -  Gastric bezoar;

               -  Crohn's disease or diverticulitis;

               -  severe dysphagia to food or pills;

               -  Food allergies and/or presence of any dietary restrictions;

               -  Severe allergic reactions (e.g. anaphylactic reactions, angioedema).

         12. History of intolerance to and/or difficulty with blood sampling through venipuncture.

         13. Abnormal diet patterns (for any reason) during the four weeks preceding the study,
             including fasting, high protein diets, vegan, etc.

         14. Individuals who have donated, in the days prior to first study period:

               -  50-499 mL of blood in the previous 30 days;

               -  500 mL or more in the previous 56 days.

         15. Donation of plasma by plasmapheresis within 7 days prior to first study period.

         16. Individuals who have participated in another clinical trial or who received an
             investigational drug within 30 days prior to first study period.

         17. Use of any enzyme-modifying drugs and/or other products, including strong inhibitors
             of cytochrome P450 (CYP) enzymes (e.g. cimetidine, fluoxetine, quinidine, fluconazole,
             ketoconazole, voriconazole, itraconazole, clarithromycin, erythromycin, nefazodone,
             atazanavir, saquinavir, indinavir, and nelfinavir) and strong inducers of CYP enzymes
             (e.g. barbiturates, carbamazepine, glucocorticoids, phenytoin, St. John´s Wort and
             rifampin) in the previous 30 days before first study period.

         18. Use of drugs such as, proton pump inhibitors, clopidogrel, tacrolimus, digoxin,
             cyclosporine, disulfiram, benzodiazepines, diazepam, warfarin, methotrexate, iron
             salts, erlotinib, and mycophenolate mofetil (MMF) in the previous 30 days before first
             study period, or individuals with vitamin B-12 deficiency (as long-term dosing (more
             than 3 years) of omeprazole/sodium bicarbonateZegerid may lead to vitamin B-12
             deficiency)

         19. Individuals having undergone gastrointestinal (GI) surgery within 3 months prior to
             first study period, unless deemed otherwise by PI/Sub-Investigator.

         20. Use of any prescription medication within 14 days prior to first study period (except
             for contraceptives).

         21. Use of any over-the-counter medications (including oral multivitamins, herbal and/or
             dietary supplements and/or teas) within 14 days prior to first study period (except
             for spermicidal/barrier contraceptive products).

         22. Consumption of food or beverages containing grapefruit and grapefruit juice and/or
             pomelo within 10 days prior to first study period.

         23. Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds
             and/or alcohol within 48 hours before dosing.

         24. Use of diuretics (drugs or food, see Appendix D) within 24 hours before dosing of
             SmartPillTM.

         25. Individuals having undergone any major surgery within 6 months prior to the start of
             the study, unless deemed otherwise by PI/Sub-Investigator.

         26. Difficulty with swallowing whole tablets or large capsules.

         27. Have had a tattoo or body piercing within 30 days prior to first study period and
             during the study.