NCT03731559

Efficacy, Safety and Pharmacokinetics of DTG with RIF

Efficacy, Safety and Pharmacokinetics of Dolutegravir 50 Mg Once Daily with Food Versus Dolutegravir 50 Mg Twice Daily in HIV/TB Co-infected Patients Receiving Rifampin-based Antituberculosis Therapy

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The overall aim of the project is to evaluate optimal DTG dose for the combined treatment of TB and HIV infections with RIF based anti-TB therapy. This Stage II trial will determine precisely the PK parameters of DTG in combination with RIF regimen in Thai HIV/TB co-infected patients. After the optimal dose of DTG has been found, it will be further tested in a larger Stage III trial to assess its safety, tolerability and efficacy when used with RIF based regimen.

Detailed description

This is a Stage II, randomized, open-label study describing the efficacy and safety of DTG 50 mg OD with food and DTG 50 mg BID plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy. The study will be conducted in approximately 200 HIV-1 infected individuals who are ART-naïve and newly diagnosed with probable or confirmed pulmonary, pleural, or lymph node (LN) Mycobacterium TB (MTB) taking RIF-containing first-line TB treatment. Subjects should have confirmed RIF-sensitive MTB infection as determined by GeneXpert (or equivalent approved molecular test) or mycobacterial culture. The study is comprised two different stages: 1. Stage1, investigators will test the safety and tolerability, as well as Pharmacokinetics (PK), of two different doses of dolutegravir co-administered with standard anti-TB treatment. Overall, 40 HIV/TB patients will be enrolled. They will be randomized to 2 groups (DTG 50 mg with food and DTG 50 mg BID). Intensive PK of DTG will be performed at week 4. Interim analysis will be performed if all 40 cases completed 12 weeks and 24 weeks. Premature study termination will be set for 1. proportion of HIV RNA \< 50 copies/ml at week 24 between 2 group is different \> 20% 2. DTG 50 mg with food has geometric mean DTG Ctrough \< 0.3 mg/L If there is no premature study termination met, the study will move to stage 2. Stage 2 will only be recruited if two different doses of dolutegravir are well tolerated and safe. 2. Stage 2: 160 HIV/TB patients will be enrolled. They will be randomized to 2 groups (DTG 50 mg with food and DTG 50 mg BID). DTG concentration will be performed at week 4 and 48. Interim analysis will be performed if all 200 cases completed 24 weeks.

Conditions

• HIV/TB Coinfection

Interventions

Type	Name	Description
DRUG	DTG 50 mg OD with food	Dolutegravir 50 mg once daily with food plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy
DRUG	DTG 50 mg BID	Dolutegravir 50 mg BID plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy.

Timeline

• Start date: 2019-06-25
• Primary completion: 2025-06-30
• Completion: 2025-06-30
• First posted: 2018-11-06
• Last updated: 2024-10-02

Locations

10 sites across 1 country: Thailand