Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

Phase 4

Completed

• Conditions: Hiv; Tuberculosis
• Interventions: Drug: Dolutegravir

• Registration Number: NCT04166474
• Lead Sponsor: Helen Reynolds

Brief Summary

This is a drug interaction study in HIV negative, TB-monoinfected participants coming to the end of continuation phase of TB therapy, to study the pharmacokinetic changes to dolutegravir when administered with standard, medium and high dose rifampicin.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-01
• Study First Submitted QC: 2019-11-14
• Study First Posted: 2019-11-18
• Study Start: 2021-11-18
• Primary Completion: 2024-02-07
• Study Completion: 2024-02-07
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-12
• Last Update Posted: 2024-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Ability to give informed consent prior to participation
• Willing and able to comply with all study requirements
• Receiving standard doses of RIF and INH
• HIV antibody negative
• Male or non-pregnant, non-breastfeeding female
• Study participation will not extend length of ATT by more than 4 weeks

Exclusion Criteria

• < 18 years
• Body weight < 50 kg
• eGFR < 60 mL/min
• Abnormal LFTs including ALT > 2.5 ULN
• HIV antibody positive
• Non-standard TB regimen (containing RHZE)
• Women of childbearing age unless using effective contraception
• Family history of sudden cardiac death
• Prior history of cardiac disease that precludes the use of low dose digoxin
• Medical or psychiatric condition that might affect participation in the study based on investigator judgement
• Regular consumption of grapefruit or grapefruit juice
• ECG abnormalities that preclude the use of low dose digoxin (intermittent complete heart block, second degree AV block, supraventricular arrhythmia associated with conducting pathways, ventricular tachycardia or fibrillation)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dolutegravir	Dolutegravir	-

Primary Outcome Measures

Name	Time	Method
Change in pharmacokinetic parameter Cmin of dolutegravir	Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment	Change in dolutegravir Cmin when dosed with standard, medium, high dose rifampicin

Secondary Outcome Measures

Name	Time	Method
Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)	From first dose of dolutegravir until study completion approximately 2 years	Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)
Change in pharmacokinetic parameter AUC of dolutegravir	Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment	Change in dolutegravir AUC when dosed with standard, medium, high dose rifampicin
Change in pharmacokinetic parameter Cmax of dolutegravir	Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment	Change in dolutegravir Cmax when dosed with standard, medium, high dose rifampicin

Trial Locations

Locations (2)

Desmond Tutu Health Foundation; 🇿🇦 Cape Town, South Africa

Infectious Diseases Institute; 🇺🇬 Kampala, Uganda