Healthy
Conditions
Brief summary
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).
Interventions
Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1
DRUGRitonavir-boosted Atazanavir plus Rabeprazole
Rabeprazole (20mg) PO twice daily (Days 1-3); Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1 (Day 4)
DRUGRitonavir-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
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area-Under-the Concentration Curve from zero-to-twenty two hours (AUC,0-22) of Atazanavir | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration of Atazanavir | 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. |
Countries
United States
Outcome results
None listed