Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetics of Atazanavir in Special Populations (VirTUAL WP5)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03923231
Recruitment Status : Not yet recruiting
First Posted : April 22, 2019
Last Update Posted : April 22, 2019
Sponsor:
Collaborators:
Infectious Diseases Institute, Makerere University College of Health Sciences
Joint Clinical Research Centre- Kampala
Desmond Tutu HIV Foundation, Cape Town
University of Cape Town
Information provided by (Responsible Party):
Catriona Waitt, University of Liverpool

Brief Summary:

The lack of data relating to the DDI between ATV and RIF is a major limitation to the use of ATV in patients who require treatment for TB. The VirTUAL Workpackage 2 will explore the necessary dose escalation required to overcome this interaction in non-pregnant HIV-infected adults who are virologically suppressed on bPI-based ART, and who are administered RIF as a study drug, not as part of a full TB treatment regimen. As the specific objective of WP2 is to define the dose of ATV, participants taking an alternative bPI will be transitioned to ATV for the duration of that study. However, to extrapolate the results of this study to special populations such as pregnant and postpartum women, children and adolescents and those with other 'special' characteristics such as obesity (BMI >30 Kg/m2) or malnutrition (BMI <18.5 Kg/m2) we propose to undertake sparse sampling for pharmacokinetic analysis from individuals who require ATV-based ART for their clinical care.

Sparse PK data will be obtained opportunistically from participants in the 'special populations' defined above who are receiving ATV as part of their routine clinical care. Subjects will be identified from clinics including the Joint Clinical Research Center (JCRC) and Infectious Diseases Institute (IDI), Kampala, and from sites including Groote Schuur Hospital and Gugulethu Community Health Centre, Cape Town. The ATV/r data from "special populations" will enable validation and refinement of both the PBPK model (WP1) and the pop-PK models (WP4) of the VirTUAL consortium.


Condition or disease Intervention/treatment
HIV/AIDS Tuberculosis Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily Drug: Atazanavir 250 mg / ritonavir 80 mg

  Show Detailed Description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Investigation of the Pharmacokinetics of Atazanavir in Pregnant Women, Individuals at Extremes of BMI, Children, and Adolescents: An Observational Study Nested Within the VirTUAL Consortium
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : November 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort Intervention/treatment
Children <5 years
Children under the age of 5 years who are receiving atazanavir as part of clinical care
Drug: Atazanavir 250 mg / ritonavir 80 mg
There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care. This dose of 250/ 80 is for participants weighing between 15 and 25 Kg

Children 6-11
Children aged 6-11 years who are receiving atazanavir as part of clinical care
Drug: Atazanavir 250 mg / ritonavir 80 mg
There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care. This dose of 250/ 80 is for participants weighing between 15 and 25 Kg

Adolescents 12-17
Adolescents aged 12-17 years who are receiving atazanavir as part of clinical care
Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily
There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care

Pregnant women
Women who are at least 20 weeks gestation, who are receiving atazanavir as part of clinical care
Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily
There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care

BMI < 18.5
Adults with a BMI of <18.5 kg/m2 who are receiving atazanavir as part of clinical care
Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily
There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care

BMI >30
Adults with a BMI of >30 kg/m2 who are receiving atazanavir as part of clinical care
Drug: Atazanavir 300mg/ Ritonavir 100 mg once daily
There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care




Primary Outcome Measures :
  1. Atazanavir Cmax [ Time Frame: 3 years ]
    To describe the maximum concentration of atazanavir reached after dosing in the different groups

  2. Atazanavir AUC0-24 [ Time Frame: 3 years ]
    To describe the area under the concentration-time curve from 0 to 24 hours after dosing in the different groups

  3. Atazanavir Ctau [ Time Frame: 3 years ]
    To describe the trough concentration of atazanavir after dosing in the different study groups


Secondary Outcome Measures :
  1. Comparison of geometric mean of atazanavir Cmax with healthy adult population [ Time Frame: 3 years ]
    To compare atazanavir Cmax with typical healthy individuals treated with atazanavir who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme

  2. Comparison of geometric mean of atazanavir AUC0-24 with healthy adult population [ Time Frame: 3 years ]
    To compare atazanavir AUC0-24 with that of typical healthy adults treated with atazanavir-based ART who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme

  3. Comparison of geometric mean of atazanavir Ctau with healthy adult population [ Time Frame: 3 years ]
    To compare atazanavir Ctau with that of typical healthy adults treated with atazanavir-based ART who enter a dose escalation study of ATV/r + RIF as WP2 of the VirTUAL programme


Other Outcome Measures:
  1. Modelling of atazanavir pharmacokinetics [ Time Frame: 4 years ]
    To use nonlinear mixed-effects modelling to describe sources of variability on the pharmacokinetics of ATV

  2. Exploratory objective: Cmax of second-line ART with TB treatment [ Time Frame: 3 years ]
    To describe the maximum concentrations of second-line antiretroviral drugs and rifamycin-containing TB therapy in HIV-infected pregnant and postpartum women, children and adolescents and individuals with extremes of BMI

  3. Exploratory objective: AUC of second-line ART with TB treatment [ Time Frame: 3 years ]
    To describe the area under the concentration-time curve of second-line antiretroviral drugs and rifamycin-containing TB therapy in HIV-infected pregnant and postpartum women, children and adolescents and individuals with extremes of BMI

  4. Exploratory objective: Ctau of second-line ART with TB treatment [ Time Frame: 3 years ]
    To describe the minimum concentration of second-line antiretroviral drugs and rifamycin-containing TB therapy in HIV-infected pregnant and postpartum women, children and adolescents and individuals with extremes of BMI



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   One of the groups of special interest is pregnant women, who will all be female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Individuals will be identified at routine clinic appointments. They (or their guardians) will be asked to keep a detailed record of dosing times for three to five days prior to their study appointment at which sampling will be performed. If they take their medication in the morning, they will be asked to bring the medication to clinic for observation of dosing.

Repeat sampling at subsequent appointments will enable assessment of both between and within-individual variability, for example during periods of rapid childhood growth or during pregnancy and transition back to non-pregnant physiological state.

Criteria

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant (or a legal representative) has been informed of all pertinent aspects of the study.
  2. In a child aged ≥7 years (South Africa) or aged ≥8 years (Uganda), evidence of assent to participate
  3. Participants who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.
  4. HIV-infected, receiving ATV-based ART treatment OR HIV-infected receiving second-line ART with concurrent rifamycin-based TB treatment
  5. Participant is within one of the target populations:

    1. Pregnant (>20 weeks)
    2. Body mass index >30 or <18.5 Kg/m2
    3. Child or adolescent aged <18 years

Exclusion Criteria:

  1. Medical, psychiatric or obstetric condition that might affect participation in the stuy based on investigator judgement
  2. Dissent from a minor
  3. For pregnant women in Uganda, where the husband is reasonably involved, paternal objection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03923231


Contacts
Layout table for location contacts
Contact: Catriona Waitt 07581417744 cwaitt@liv.ac.uk
Contact: Henry Mugerwa hmugerwa@jcrc.org.ug

Locations
Layout table for location information
South Africa
Desmond Tutu HIV Foundation
Cape Town, Western Cape, South Africa
University of Cape Town
Cape Town, Western Cape, South Africa
Uganda
Infectious Diseases Institute
Kampala, Uganda
Joint Clinical Research Centre Not yet recruiting
Kampala, Uganda
Contact: Henry Mugerwa       hmugerwa@jcrc.org.ug   
Sponsors and Collaborators
University of Liverpool
Infectious Diseases Institute, Makerere University College of Health Sciences
Joint Clinical Research Centre- Kampala
Desmond Tutu HIV Foundation, Cape Town
University of Cape Town

Layout table for additonal information
Responsible Party: Catriona Waitt, Senior Lecturer in Clinical Pharmacology, University of Liverpool
ClinicalTrials.gov Identifier: NCT03923231     History of Changes
Other Study ID Numbers: VirTUAL WP5
First Posted: April 22, 2019    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Ritonavir
Atazanavir Sulfate
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors