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

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

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).

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: atazanavir 300mg boosted with ritonavir 50 mg

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: atazanavir 300mg boosted with ritonavir 100mg; 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: Norvir; Reyataz; RTV; ATV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	main pharmacokinetic parameters of atazanavir: AUC0-24h, Cmax and Cmin.	9 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	the main pharmacokinetic parameters of ritonavir: AUC0-24h, Cmax and Cmin, , adverse events and preference, as reported by patients during the study period.	9 days

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: William Cameron, MD, FRCPC, The Ottawa Hospital

Publications and helpful links

Helpful Links

• Info on The Ottawa Hospital -General Campus Clinical Investigation Unit

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 10, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (Estimate): January 14, 2014

Study Record Updates

• Last Update Posted (Estimate): September 22, 2015
• Last Update Submitted That Met QC Criteria: September 21, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: PK; pharmacokinetic; ritonavir; HIV-infected; atazanavir
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: AI424-979; 20130609-01H (Other Identifier: Ottawa Hospital Research Institute)