Effects of Gastric pH on the Pharmacokinetics of Atazanavir

Study Overview
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Brief Summary
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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).

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ritonavir-boosted Atazanavir
* Drug: Ritonavir-boosted Atazanavir plus Rabeprazole
* Drug: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ritonavir-boosted Atazanavir<br> | Drug: Ritonavir-boosted Atazanavir<br>* Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1<br>|
| Experimental: Ritonavir-boosted Atazanavir plus Rabeprazole<br> | Drug: Ritonavir-boosted Atazanavir plus Rabeprazole<br>* Rabeprazole (20mg) PO twice daily (Days 1-3); Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1 (Day 4)<br>|
| Experimental: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine HCl<br> | Drug: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride<br>* 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<br>|

What is the study measuring?
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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 |