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Effects of Gastric pH on the Pharmacokinetics of Atazanavir

This study is currently recruiting participants.
Verified January 2013 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
Leslie Benet, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01759875
First received: December 30, 2012
Last updated: January 9, 2013
Last verified: January 2013
History of Changes
  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:

U.S. FDA Resources

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

Contacts
Contact: Kathleen P Faber, B.S. 415-502-6717 kate.faber@ucsf.edu
Contact: Lynda Frassetto, M.D. 415-476-6143 frassett@gcrc.ucsf.edu

Locations
United States, California
Clinical Research Center, UCSF Recruiting
San Francisco, California, United States, 94143
Contact: Kathleen P Faber, B.S.     415-502-6717     kate.faber@ucsf.edu    
Contact: Lynda Frassetto, M.D.     415-476-6143     frassett@gcrc.ucsf.edu    
Principal Investigator: Leslie Z Benet, Ph.D            
Principal Investigator: Lynda Frassetto, M.D.            
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: January 9, 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 May 16, 2013