Pharmacokinetics of Atazanavir in Special Populations

NCT03923231 | Completed

• 1 other identifier: VirTUAL WP5
• Study Type: observational
• Target: 32
• Locations: 2 countries
• Sites: 4

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.

Conditions

HIV/AIDS; Tuberculosis

Outcome Measures

Primary Outcomes (3)

• Atazanavir Cmax

  To describe the maximum concentration of atazanavir reached after dosing in the different groups

  3 years

• Atazanavir AUC0-24

  To describe the area under the concentration-time curve from 0 to 24 hours after dosing in the different groups

  3 years

• Atazanavir Ctau

  To describe the trough concentration of atazanavir after dosing in the different study groups

  3 years

Secondary Outcomes (3)

• Comparison of geometric mean of atazanavir Cmax with healthy adult population

  3 years

• Comparison of geometric mean of atazanavir AUC0-24 with healthy adult population

  3 years

• Comparison of geometric mean of atazanavir Ctau with healthy adult population

  3 years

Other Outcomes (4)

• Modelling of atazanavir pharmacokinetics

  4 years

• Exploratory objective: Cmax of second-line ART with TB treatment

  3 years

• Exploratory objective: AUC of second-line ART with TB treatment

  3 years

Study Arms (6)

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

Children 6-11

Children aged 6-11 years who are receiving atazanavir as part of clinical care

Drug: Atazanavir 250 mg / ritonavir 80 mg

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

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

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

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

Interventions

Atazanavir 300mg/ Ritonavir 100 mg once daily DRUG

There is no intervention in this study - participants will all be receiving atazanavir (usually boosted with ritonavir) as part of their routine clinical care

Adolescents 12-17; BMI < 18.5; BMI >30; Pregnant women

Atazanavir 250 mg / ritonavir 80 mg DRUG

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 <5 years

Eligibility Criteria

• Gender Eligibility Details: One of the groups of special interest is pregnant women, who will all be female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.
• In a child aged ≥7 years (South Africa) or aged ≥8 years (Uganda), evidence of assent to participate
• Participants who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.
• HIV-infected, receiving ATV-based ART treatment OR HIV-infected receiving second-line ART with concurrent rifamycin-based TB treatment
• Participant is within one of the target populations:
• Pregnant (\>20 weeks)
• Body mass index \>30 or \<18.5 Kg/m2
• Child or adolescent aged \<18 years

You may not qualify if:

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

Sponsors & Collaborators

• University of Liverpool: lead
• Makerere University: collaborator
• Joint Clinical Research Centre- Kampala: collaborator
• Desmond Tutu HIV Foundation: collaborator
• University of Cape Town: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP) - funder: collaborator

Study Sites (4)

Desmond Tutu HIV Foundation

Cape Town, Western Cape, South Africa

Location

University of Cape Town

Cape Town, Western Cape, South Africa

Location

Infectious Diseases Institute

Kampala, Uganda

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Tuberculosis

Interventions

Atazanavir Sulfate; Ritonavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Clinical Pharmacology

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 22, 2019
• Study Start: September 2, 2019
• Primary Completion: May 1, 2020
• Study Completion: November 30, 2022
• Last Updated: May 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

UG (2); ZA (2)