Clinical trial NCT04746547: Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB
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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Tuberculosis
Hiv
Keywords: Dolutegravir (DTG)
Paediatrics
HIV/TB co-infection
Lead sponsor: University of KwaZulu
Sponsor class: OTHER
Collaborators: name: Centre for the AIDS Programme of Research in South Africa
First posted: 2021-02-09
Enrollment: 20
Sex: ALL
Minimum age (years): 23
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pharmacokinetic evaluation of DTG in children receiving Rifampicin containing TB treatment
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Pharmacokinetics (Ctrough) of DTG 50mg twice daily
timeFrame: 48 weeks
measure: Pharmacokinetics (Cmax) of DTG 50mg twice daily
timeFrame: 48 weeks
measure: Pharmacokinetics (AUC0-24h) of DTG 50mg twice daily
timeFrame: 48 weeks
Secondary outcomes:
measure: To develop an integrated model which will be used to estimate the primary PK parameters of DTG
timeFrame: 48 weeks
measure: Adverse events
timeFrame: 48 weeks
measure: Virological suppression
timeFrame: 48 weeks
measure: Enzyme polymorphisms
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Durban
country: South Africa
facility: King Edward VIII Hospital
state: KwaZulu-Natal
Study officials:
affiliation: University of KwaZulu
name: Moherndran Archary, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References: