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

NCT04746547 | Unknown Phase 4 DMC

• 1 other identifier: CAPRISA258 (CAP258)
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Tuberculosis; Hiv

Keywords

Dolutegravir (DTG); Paediatrics; HIV/TB co-infection

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  48 weeks

Secondary Outcomes (4)

• To develop an integrated model which will be used to estimate the primary PK parameters of DTG

  48 weeks

• Adverse events

  48 weeks

• Virological suppression

  48 weeks

• Enzyme polymorphisms

  48 weeks

Study Arms (1)

Twice Daily DTG

OTHER

Twice daily Dolutegravir (50mg) with Rifampicin containing TB treatment / Twice daily Dolutegravir (10mg) dispersible

Drug: Dolutegravir 50 MG; Drug: Dolutegravir 10 MG

Interventions

Dolutegravir 50 MG DRUG

Twice daily dolutegravir with rifampicin containing TB treatment

Twice Daily DTG

Dolutegravir 10 MG DRUG

Twice daily dolutegravir with rifampicin containing TB treatment

Twice Daily DTG

Eligibility Criteria

• Age: 23 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of KwaZulu: lead
• Centre for the AIDS Programme of Research in South Africa: collaborator

Study Sites (1)

King Edward VIII Hospital

Durban, KwaZulu-Natal, 4001, South Africa

RECRUITING

Related Publications (1)

• 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.

  PMID: 40023169 DERIVED

MeSH Terms

Conditions

Tuberculosis; Acquired Immunodeficiency Syndrome

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; 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

Study Officials

• Moherndran Archary, MBChB, PhD

  University of KwaZulu

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Moherndran Archary, MBChB, PhD

CONTACT

+27312604318; archary@ukzn.ac.za

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Moherndran Archary

Model Details: Pharmacokinetic evaluation of DTG in children receiving Rifampicin containing TB treatment

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 9, 2021
• Study Start: August 19, 2021
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: February 1, 2024

Record last verified: 2024-01

Locations

ZA (1)