Effects of Gastric pH on the Pharmacokinetics of Atazanavir

Overview

The goal of this study is to evaluate the ability of a natural supplement (betaine hydrochloride) to affect the absorption of atazanavir in healthy volunteers. The investigators predict that betaine hydrochloride will increase the absorption of atazanavir in volunteers pre-treated with proton-pump inhibitors (PPIs).

Full Title of Study: “Effects of Gastric pH on the Pharmacokinetics of Atazanavir in Healthy Volunteers”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 2014

Interventions

  • Drug: Ritonavir-boosted Atazanavir
    • Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1
  • Drug: Ritonavir-boosted Atazanavir plus Rabeprazole
    • Rabeprazole (20mg) PO twice daily (Days 1-3); Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1 (Day 4)
  • Drug: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride
    • Rabeprazole (20mg) PO twice daily (Days 1-3); Betaine Hydrochloride (1500mg) PO x1 AND Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1 on Day 4

Arms, Groups and Cohorts

  • Active Comparator: Ritonavir-boosted Atazanavir
  • Experimental: Ritonavir-boosted Atazanavir plus Rabeprazole
  • Experimental: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine HCl

Clinical Trial Outcome Measures

Primary Measures

  • Area-Under-the Concentration Curve from zero-to-twenty two hours (AUC,0-22) of Atazanavir
    • Time Frame: Day 4
    • The primary outcome measure will be atazanavir area-under-the-concentration curve (AUC) values from zero-to-twenty two (0-22) hours. Values from Experimental Arms of the study (Ritonavir-boosted Atazanavir plus Rabeprazole; Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (Ritonavir-boosted atazanavir alone) and tested for statistical significance.
  • Area-Under-the Concentration Curve from zero-to-infinity (AUC,0-inf) of Atazanavir
    • Time Frame: Day 4
    • The primary outcome measure will be atazanavir area-under-the-concentration curve (AUC) values from zero-to-infinite time (0-inf). Values from Experimental Arms of the study (Ritonavir-boosted Atazanavir plus Rabeprazole; Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (Ritonavir-boosted Atazanavir alone) and tested for statistical significance.

Secondary Measures

  • Maximum Concentration of Atazanavir
    • Time Frame: Day 4
    • The maximum plasma concentration (Cmax) will also be measured. Values from Experimental Arms of the study (Ritonavir-boosted Atazanavir plus Rabeprazole; Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride) will be compared against the active comparator (Ritonavir-boosted Atazanavir alone) and tested for statistical significance.

Participating in This Clinical Trial

Inclusion Criteria

  • Male or female 18-65 years of age – Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on history, physical exam and laboratory evaluations – BMI between 18.5-30 kg/m2 – Taking no medications 2 weeks before and during the study enrollment, including drugs of abuse, prescription or over-the-counter (OTC) medications (except acetaminophen) – Subjects able to maintain adequate birth control during the study independent of hormonal contraceptive use – Be able to provide written informed consent and comply with requirements of the study – Avoid eating grapefruit and drinking grapefruit juice from 7 days before the first study day until the completion of the entire study – Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 3pm the night before a study day until completion of that study day – Fast from food and beverages at least 8 hours prior to medication dosing – Be able to read, speak, and understand English Exclusion Criteria:

  • Subjects with a history of gastrointestinal disease including gastroesophageal reflux disease, gastritis, peptic ulcer disease, or dyspepsia – Subjects with a fasting gastric pH of > 4 (i.e. hypochlorhydria) – Subjects with a history of dysphagia, achalasia, or difficulty swallowing capsules, tablets, or pills – Subjects on prescription or chronic over-the-counter (OTC) medications (including hormonal contraceptives) – Subjects with known allergies rabeprazole, any other proton pump inhibitors (PPI's) or betaine hydrochloride – Subjects who smoke tobacco – Subjects with ongoing alcohol or illegal drug use – Subjects who are pregnant, lactating, or attempting to conceive – Subjects unable to maintain adequate birth control during the study

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of California, San Francisco
  • Provider of Information About this Clinical Study
    • Sponsor

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