Microboosting of Atazanavir 300 mg With 50 mg Versus 100mg Ritonavir Daily in HIV-infected Patients: a Pharmacokinetic Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Ottawa Hospital Research Institute
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT02034838
First received: January 10, 2014
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

This is an open-label, single group study to determine the pharmacokinetic profile of atazanavir 300 mg daily boosted with ritonavir 100mg daily in HIV-infected patients over a period of 9 days.

Ritonavir and atazanavir are protease inhibitors used to treat HIV. However, ritonavir, when used at low doses (up to 100mg) does not have HIV activity, but will enhance (boost) the blood concentrations of other drugs like atazanavir.

Recently, a study showed that taking 50mg of ritonavir administered in an oral solution led to similar blood concentrations of atazanavir than when given with 100mg of ritonavir. Potential benefits associated with a lower dose of ritonavir may include a reduction of side effects such as upset stomach and an improvement in cholesterol level. This study will look at the amount of atazanavir into your blood when given with ritonavir in a tablet formulation at 50mg or 100mg with standard atazanavir dose (300mg).


Condition Intervention Phase
HIV Infection
Drug: atazanavir 300mg boosted with ritonavir 50 mg
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Microboosting of Atazanavir 300 mg With 50 mg Versus 100 mg Ritonavir Daily in HIV-infected Patients: a Pharmacokinetic Study

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 9 days ] [ Designated as safety issue: No ]
    main pharmacokinetic parameters of atazanavir: AUC0-24h, Cmax and Cmin.


Secondary Outcome Measures:
  • adverse events [ Time Frame: 9 days ] [ Designated as safety issue: Yes ]
    the main pharmacokinetic parameters of ritonavir: AUC0-24h, Cmax and Cmin, , adverse events and preference, as reported by patients during the study period.


Estimated Enrollment: 12
Study Start Date: January 2014
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: atazanavir boosted with ritonavir

Two period drug interaction. Period one: atazanavir 300mg boosted with ritonavir 100 mg once daily as part of current treatment standard of care.

Period two: atazanavir 300 mg boosted with ritonavir 50 mg once daily for study days 2-8 inclusive

Drug: atazanavir 300mg boosted with ritonavir 50 mg

atazanavir 300 mg with ritonavir 100 mg once a day at 8:00 am for study day 1 and 9.

atazanavir 300 mg with ritonavir 50 mg once a day at 8:00 am for 7 consecutive days (study days 2-8)

Other Names:
  • Reyataz
  • ATV
  • Norvir
  • RTV

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients meeting the following criteria will be eligible for participation in this study:

    1. Signed informed consent prior to any study-related activities.
    2. Documented HIV infection.
    3. Male or female patients between 18 and 70 years of age inclusively.
    4. Medication history, vital signs and physical exam adequately showing no signs of acute illness at screening, as per the assessment by the physician.
    5. Patients must be willing to stop using any herbal or natural health products for 4 weeks prior to and during the study including:

      • Grapefruit, grapefruit juice, St. John's Wort and any others as determined by the investigators.
    6. Patients must be on an antiretroviral regimen with atazanavir/ ritonavir 300/100 mg daily as the only protease inhibitor plus any combination of nucleoside reverse transcriptase inhibitors, for at least four weeks.
    7. VL<40 copies/mL on the most recent measurement, during treatment with atazanavir 300 mg daily and ritonavir 100 mg daily, which must be within 12 weeks of the study start date.
    8. Reproductive Status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below).

      • WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
      • WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 0 to 72 hours before the first dose of study drug.
      • Women must not be breast-feeding.
      • Sexually active fertile men must use effective birth control if their partners are WOCBP

Exclusion Criteria:

Patients meeting one or more of the following criteria will be excluded from the study:

  1. Female patients of childbearing potential who:

    1. Has a positive urine pregnancy test at screening.
    2. Have not been using a barrier method of contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), for at least 3 months prior to participation in the study.
    3. Is not willing or able to use a reliable method of barrier contraception during the study.
    4. Is breastfeeding.
  2. Patients with prior history of treatment failure on a PI based regimen, or with genotypic evidence of resistance associated mutations to protease inhibitors.
  3. Use of any medication listed in Appendix I within 4 weeks prior to screening.
  4. Use of any over-the-counter or prescription medications in the two weeks prior to Day 1 of the study that may interfere with absorption, distribution, metabolism or excretion of the study medications.
  5. Inability to adhere to protocol.
  6. Patients may be excluded from the study for other reasons, at the investigator's discretion.
  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: NCT02034838

Contacts
Contact: Pierre Giguère, BPharm, MSc 613-737-8922 pgiguere@toh.on.ca
Contact: William Cameron, MD, FRCPC 613-737-8923 bcameron@ohri.ca

Locations
Canada, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Pierre Giguère, BPharm, MSc    613-737-8922    pgiguere@toh.on.ca   
Principal Investigator: Bill Cameron, MD         
Sub-Investigator: Pierre Giguere, BPharm, MSc         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: William Cameron, MD, FRCPC The Ottawa Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT02034838     History of Changes
Other Study ID Numbers: AI424-979, 20130609-01H
Study First Received: January 10, 2014
Last Updated: January 13, 2014
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
PK
pharmacokinetic
HIV-infected
atazanavir
ritonavir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Atazanavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014