Effects of Gastric pH on the Pharmacokinetics of Atazanavir

Effects of Gastric pH on the Pharmacokinetics of Atazanavir in Healthy Volunteers

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ritonavir-boosted Atazanavir; Drug: Ritonavir-boosted Atazanavir plus Rabeprazole; Drug: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Clinical Research Center, UCSF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ritonavir-boosted Atazanavir	Drug: Ritonavir-boosted Atazanavir; Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1
Experimental: Ritonavir-boosted Atazanavir plus Rabeprazole	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)
Experimental: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine HCl	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area-Under-the Concentration Curve from zero-to-twenty two hours (AUC,0-22) of Atazanavir	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.	Day 4
Area-Under-the Concentration Curve from zero-to-infinity (AUC,0-inf) of Atazanavir	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.	Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration of Atazanavir	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.	Day 4

Collaborators and Investigators

• Sponsor: University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 30, 2012
• First Submitted That Met QC Criteria: December 30, 2012
• First Posted (Estimate): January 3, 2013

Study Record Updates

• Last Update Posted (Estimate): April 28, 2015
• Last Update Submitted That Met QC Criteria: April 24, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Gastrointestinal Agents; Protease Inhibitors; Hypolipidemic Agents; Lipid Regulating Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lipotropic Agents; Ritonavir; Rabeprazole; Atazanavir Sulfate; Betaine
• Other Study ID Numbers: CRS6537