TuberculosisPhase 4ORCHIDNCT04746547
Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB
A Phase 4 study testing Dolutegravir 50 MG and Dolutegravir 10 MG in people with Tuberculosis and Hiv, run by University of KwaZulu at 1 site in South Africa.
Trial 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. Note: An amendment has been added to include children from 3kgs and a dose of 10mg dispersible DTG Read more about this study
- Who is it for?
- Ages 23 months to 18 years
- Conditions the study is for
- Tuberculosis, Hiv
- What is being tested?
- Dolutegravir 50 MG and Dolutegravir 10 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Africa
- Study dates
- 19 Aug 2021to 31 Jul 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
King Edward VIII Hospital
Durban, KwaZulu-Natal, 4001
Shashikant Dr Ramji, MBChB, +27313603854, Shashikant.Ramji@kznhealth.gov.za
Wendy Ms Madondo, +27313603854, Wendy.Madondo@kznhealth.gov.za
About this study
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
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.
Note: An amendment has been added to include children from 3kgs and a dose of 10mg dispersible DTG
Read the 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.
- Conditions
- Tuberculosis, Hiv
- Being tested
- Dolutegravir 50 MG, Dolutegravir 10 MG
- Keywords
- Dolutegravir (DTG), Paediatrics, HIV/TB co-infection
- Medical subject headings
- Tuberculosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir 50 MGDrug
Twice daily dolutegravir with rifampicin containing TB treatment
Dolutegravir 10 MGDrug
Twice daily dolutegravir with rifampicin containing TB treatment
| Study group | Role | What they receive |
|---|---|---|
| Twice Daily DTG | Other | Twice daily Dolutegravir (50mg) with Rifampicin containing TB treatment / Twice daily Dolutegravir (10mg) dispersible Receives: Drug: Dolutegravir 50 MG; Drug: Dolutegravir 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 weeks
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.
Measured: 48 weeks
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.
Measured: 48 weeks
Secondary outcomes (4)
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.
Measured: 48 weeks
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
Measured: 48 weeks
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
Measured: 48 weeks
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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2021
- Study start19 Aug 2021
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Pharmacokinetic evaluation of DTG in children receiving Rifampicin containing TB treatment
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of KwaZulu
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for the AIDS Programme of Research in South Africa
- Responsible party
- Principal investigator, Dr Moherndran Archary, University of KwaZulu
- Investigators
- Moherndran Archary, MBChB, PhD, Principal investigator, University of KwaZulu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04746547
- Sponsor's protocol ID
- CAPRISA258 (CAP258)
- Acronym
- ORCHID
- Status last verified
- Jan 2024
- First submitted
- 1 Feb 2021
- Last updated
- 1 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Naidoo A, Waalewijn H, Naidoo K, Letsoalo M, Cromhout G, Sewnarain L, Mosia NR, Osuala EC, Wiesner L, Wasmann RE, Denti P, Dooley KE, Archary M; ORCHID study team. Pharmacokinetics and safety of dolutegravir in children receiving rifampicin tuberculosis treatment in South Africa (ORCHID): a prospective cohort study. Lancet HIV. 2025 Apr;12(4):e273-e282. doi: 10.1016/S2352-3018(24)00312-6. Epub 2025 Feb 26.
PubMed 40023169
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04746547
- Acronym / sponsor ID
- ORCHID / CAPRISA258 (CAP258)
- Conditions
- Tuberculosis, Hiv
- Keywords
- Dolutegravir (DTG), Paediatrics, HIV/TB co-infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of KwaZuluUniversity, hospital or other
- Collaborators
- Centre for the AIDS Programme of Research in South Africa
- Study start
- 19 Aug 2021 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 9 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Note: An amendment has been added to include children from 3kgs and a dose of 10mg dispersible DTG
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Pharmacokinetic evaluation of DTG in children receiving Rifampicin containing TB treatment
| Arm | Type | Receives |
|---|---|---|
| Twice Daily DTG | Other | Drug: Dolutegravir 50 MG, Drug: Dolutegravir 10 MGTwice daily Dolutegravir (50mg) with Rifampicin containing TB treatment / Twice daily Dolutegravir (10mg) dispersible |
Who may qualify
- Ages
- 23 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dolutegravir 50 MGTwice daily dolutegravir with rifampicin containing TB treatment | Drug | Twice Daily DTG |
| Dolutegravir 10 MGTwice daily dolutegravir with rifampicin containing TB treatment | Drug | Twice Daily DTG |
Primary outcome
Pharmacokinetics (Ctrough) of DTG 50mg twice daily
Time frame: 48 weeks
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
Time frame: 48 weeks
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
Time frame: 48 weeks
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.
4 secondary outcomes
To develop an integrated model which will be used to estimate the primary PK parameters of DTG
Time frame: 48 weeks
Adverse events
Time frame: 48 weeks
Virological suppression
Time frame: 48 weeks
Enzyme polymorphisms
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Derived from this study: PubMed 40023169Naidoo A, Waalewijn H, Naidoo K, Letsoalo M, Cromhout G, Sewnarain L, Mosia NR, Osuala EC, Wiesner L, Wasmann RE, Denti P, Dooley KE, Archary M; ORCHID study team. Pharmacokinetics and safety of dolutegravir in children receiving rifampicin tuberculosis treatment in South Africa (ORCHID): a prospective cohort study. Lancet HIV. 2025 Apr;12(4):e273-e282. doi: 10.1016/S2352-3018(24)00312-6. Epub 2025 Feb 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Moherndran Archary, MBChB, PhD principal investigator
University of KwaZulu
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dolutegravir 50 MG and Dolutegravir 10 MG in people with Tuberculosis and Hiv, run by University of KwaZulu at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Moherndran Archary, MBChB, PhD (+27312604318, archary@ukzn.ac.za), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics (Ctrough) of DTG 50mg twice daily (time frame: 48 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04746547, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2024.