search
Back to results

Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB (ORCHID)

Primary Purpose

Tuberculosis, Hiv

Status
Recruiting
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
Dolutegravir 50 MG
Sponsored by
University of KwaZulu
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Dolutegravir (DTG), Paediatrics, HIV/TB co-infection

Eligibility Criteria

23 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children <18 years with confirmed HIV-1 infection weighing 20-35kg ART-naive or experienced, with plans to use DTG for HIV treatment
  • Diagnosis of TB disease with clinician initiating rifampicin-containing first-line therapy
  • Parents/legal guardians/caregivers and children give informed written consent (or assent, where applicable) to be in the study
  • Girls who have reached menses must have a negative pregnancy test at screening and be willing to adhere to two effective methods of contraception (barrier and a non-barrier form of contraception during the study, starting at least 14 days prior to enrolment) if sexually active. The parents/caregivers will be counselled together with the child if the child tests positive in order to reduce any social harm which may arise.

Exclusion Criteria:

  • History or presence of known allergy or contraindications to DTG
  • Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN and bilirubin ≥2xULN
  • Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones)
  • Pregnancy or breastfeeding
  • A concurrent illness that could influence drug PK, i.e. severe diarrhoea, vomiting, renal or liver disease
  • Treatment with concomitant medications known to have interactions with DTG
  • Participants that are eligible for the study but refuse to give consent and/or assent

Sites / Locations

  • King Edward VIII HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Twice Daily DTG

Arm Description

Twice daily Dolutegravir (50mg) with Rifampicin containing TB treatment

Outcomes

Primary Outcome Measures

Pharmacokinetics (Ctrough) of DTG 50mg twice daily
Description of the pharmacokinetics (Ctrough, Cmax and AUC0-24h) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Pharmacokinetics (Cmax) of DTG 50mg twice daily
Description of the pharmacokinetics (Cmax) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Pharmacokinetics (AUC0-24h) of DTG 50mg twice daily
Description of the pharmacokinetics (AUC0-24h) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.

Secondary Outcome Measures

To develop an integrated model which will be used to estimate the primary PK parameters of DTG
Nonlinear mixed-effects models (NLMEM) will be used to describe the PK of DTG in an integrated model which will be used to estimate the primary PK parameters of DTG. The effect of concomitant TB treatment, as well as other covariates on these parameters, will be evaluated in the model.
Adverse events
Subjects will be monitored clinically and biologically for safety. Biological monitoring will focus on liver function. Adverse Events and Serious Adverse Events will be graded following DAIDS grading tables
Virological suppression
Antiretroviral efficacy is based on HIV viral suppression. The cut-off value related to virological failure is defined as a viral load superior to 400 copies per mL, confirmed within a month. Viral load will be assessed as per the SOE
Enzyme polymorphisms
Enzyme polymorphism analysis will be conducted at a later stage from stored samples to determine the importance of polymorphisms in genes regulating anti-TB drug and antiretroviral concentrations and effects in the study population.

Full Information

First Posted
February 1, 2021
Last Updated
May 18, 2022
Sponsor
University of KwaZulu
Collaborators
Centre for the AIDS Programme of Research in South Africa
search

1. Study Identification

Unique Protocol Identification Number
NCT04746547
Brief Title
Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB
Acronym
ORCHID
Official Title
An Open-label, Sequential Non-randomised Pharmacokinetics Study of DTG Plasma Exposure When Given as Twice or Once Daily DTG in the Presence of Rifampicin in Children With HIV and TB Between 20-35kgs in SA
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 19, 2021 (Actual)
Primary Completion Date
August 31, 2022 (Anticipated)
Study Completion Date
February 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of KwaZulu
Collaborators
Centre for the AIDS Programme of Research in South Africa

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Stage 1 proposed study will provide evidence to support the use of twice-daily dose 50mg DTG in children (20-35kgs) co-treated with RIF.
Detailed Description
This is a single centre, open-label, non-randomised, prospective study evaluating the steady-state pharmacokinetics of twice-daily dose DTG administered during concurrent RIF treatment and assessing safety and tolerance in HIV-TB co-infected children weighing 20 to 35 kg. DTG will be administered as a twice-daily dose 50mg tablet formulation both before starting and after completion of the standard six-month RIF-based anti-TB treatment. The NRTI background and anti-TB drugs will be prescribed following the national weight band dosing guidelines. Those initially diagnosed with TB are likely to be sicker, and the recommendation is to start anti-TB treatment first and follow with ART two weeks later.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Hiv
Keywords
Dolutegravir (DTG), Paediatrics, HIV/TB co-infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Pharmacokinetic evaluation of DTG in children receiving Rifampicin containing TB treatment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Twice Daily DTG
Arm Type
Other
Arm Description
Twice daily Dolutegravir (50mg) with Rifampicin containing TB treatment
Intervention Type
Drug
Intervention Name(s)
Dolutegravir 50 MG
Intervention Description
Twice daily dolutegravir with rifampicin containing TB treatment
Primary Outcome Measure Information:
Title
Pharmacokinetics (Ctrough) of DTG 50mg twice daily
Description
Description of the pharmacokinetics (Ctrough, Cmax and AUC0-24h) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Time Frame
48 weeks
Title
Pharmacokinetics (Cmax) of DTG 50mg twice daily
Description
Description of the pharmacokinetics (Cmax) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Time Frame
48 weeks
Title
Pharmacokinetics (AUC0-24h) of DTG 50mg twice daily
Description
Description of the pharmacokinetics (AUC0-24h) of DTG 50mg twice daily in children (20-35kg) who are taking rifampicin-based regimen for the treatment of tuberculosis.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
To develop an integrated model which will be used to estimate the primary PK parameters of DTG
Description
Nonlinear mixed-effects models (NLMEM) will be used to describe the PK of DTG in an integrated model which will be used to estimate the primary PK parameters of DTG. The effect of concomitant TB treatment, as well as other covariates on these parameters, will be evaluated in the model.
Time Frame
48 weeks
Title
Adverse events
Description
Subjects will be monitored clinically and biologically for safety. Biological monitoring will focus on liver function. Adverse Events and Serious Adverse Events will be graded following DAIDS grading tables
Time Frame
48 weeks
Title
Virological suppression
Description
Antiretroviral efficacy is based on HIV viral suppression. The cut-off value related to virological failure is defined as a viral load superior to 400 copies per mL, confirmed within a month. Viral load will be assessed as per the SOE
Time Frame
48 weeks
Title
Enzyme polymorphisms
Description
Enzyme polymorphism analysis will be conducted at a later stage from stored samples to determine the importance of polymorphisms in genes regulating anti-TB drug and antiretroviral concentrations and effects in the study population.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
23 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children <18 years with confirmed HIV-1 infection weighing 20-35kg ART-naive or experienced, with plans to use DTG for HIV treatment Diagnosis of TB disease with clinician initiating rifampicin-containing first-line therapy Parents/legal guardians/caregivers and children give informed written consent (or assent, where applicable) to be in the study Girls who have reached menses must have a negative pregnancy test at screening and be willing to adhere to two effective methods of contraception (barrier and a non-barrier form of contraception during the study, starting at least 14 days prior to enrolment) if sexually active. The parents/caregivers will be counselled together with the child if the child tests positive in order to reduce any social harm which may arise. Exclusion Criteria: History or presence of known allergy or contraindications to DTG Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN and bilirubin ≥2xULN Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones) Pregnancy or breastfeeding A concurrent illness that could influence drug PK, i.e. severe diarrhoea, vomiting, renal or liver disease Treatment with concomitant medications known to have interactions with DTG Participants that are eligible for the study but refuse to give consent and/or assent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Moherndran Archary, MBChB, PhD
Phone
+27312604318
Email
archary@ukzn.ac.za
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Moherndran Archary, MBChB, PhD
Organizational Affiliation
University of KwaZulu
Official's Role
Principal Investigator
Facility Information:
Facility Name
King Edward VIII Hospital
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
4001
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shashikant Dr Ramji, MBChB
Phone
+27313603854
Email
Shashikant.Ramji@kznhealth.gov.za
First Name & Middle Initial & Last Name & Degree
Wendy Ms Madondo
Phone
+27313603854
Email
Wendy.Madondo@kznhealth.gov.za
First Name & Middle Initial & Last Name & Degree
Moherndran Archary, MBChB, PhD
First Name & Middle Initial & Last Name & Degree
Naidoo Anushka, PhD
First Name & Middle Initial & Last Name & Degree
Dooley Kelly, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB

We'll reach out to this number within 24 hrs