Effects of Gastric pH on the Pharmacokinetics of Atazanavir

NCT01759875 | Completed Phase 1

• 1 other identifier: CRS6537
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Maximum Concentration of Atazanavir

  Day 4

Study Arms (3)

Ritonavir-boosted Atazanavir

ACTIVE COMPARATOR

Drug: Ritonavir-boosted Atazanavir

Ritonavir-boosted Atazanavir plus Rabeprazole

EXPERIMENTAL

Drug: Ritonavir-boosted Atazanavir plus Rabeprazole

Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine HCl

EXPERIMENTAL

Drug: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride

Interventions

Ritonavir-boosted Atazanavir DRUG

Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1

Ritonavir-boosted Atazanavir

Ritonavir-boosted Atazanavir plus Rabeprazole DRUG

Rabeprazole (20mg) PO twice daily (Days 1-3); Ritonavir (100mg) PO x1 and Atazanavir (300mg) PO x1 (Day 4)

Ritonavir-boosted Atazanavir plus Rabeprazole

Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride DRUG

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

Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine HCl

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

Clinical Research Center, UCSF

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

Rabeprazole; Betaine

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Onium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2012
• First Posted: January 3, 2013
• Study Start: January 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 28, 2015

Record last verified: 2015-04

Locations

US (1)