Effects of Gastric pH on the Pharmacokinetics of Atazanavir

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Leslie Benet, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01759875
First received: December 30, 2012
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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).


Condition Intervention Phase
Healthy
Drug: Ritonavir-boosted Atazanavir
Drug: Ritonavir-boosted Atazanavir plus Rabeprazole
Drug: Ritonavir-boosted Atazanavir plus Rabeprazole AND Betaine Hydrochloride
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Gastric pH on the Pharmacokinetics of Atazanavir in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Area-Under-the Concentration Curve from zero-to-twenty two hours (AUC,0-22) of Atazanavir [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Maximum Concentration of Atazanavir [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 8
Study Start Date: January 2013
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01759875

Locations
United States, California
Clinical Research Center, UCSF
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
  More Information

No publications provided

Responsible Party: Leslie Benet, Professor, Bioengineering and Therapeutic Science, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01759875     History of Changes
Other Study ID Numbers: CRS6537
Study First Received: December 30, 2012
Last Updated: September 26, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Rabeprazole
Betaine
Ritonavir
Atazanavir
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors
Anti-Ulcer Agents
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 22, 2014