Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

Hiv Clinical Trial

— DoRIS  

Official title:

Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04166474
• Other study ID #: UoL001452
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 18, 2021
• Est. completion date: April 2024

Study information

• Verified date: November 2023
• Source: University of Liverpool
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: April 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hiv
• Tuberculosis

Intervention

Drug:
• Dolutegravir
Dosed at 50 mg bd on 3 separate occasions with low, medium and high doses of rifampicin. Dosed at 50 mg od without rifampicin.

Locations

Country	Name	City	State
South Africa	Desmond Tutu Health Foundation	Cape Town
Uganda	Infectious Diseases Institute	Kampala

Sponsors (3)

Lead Sponsor	Collaborator
Helen Reynolds	Desmond Tutu HIV Centre, Infectious Disease Institute, Kampala, Uganda

Countries where clinical trial is conducted

South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pharmacokinetic parameter Cmin of dolutegravir	Change in dolutegravir Cmin when dosed with standard, medium, high dose rifampicin	Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment
Secondary	Change in pharmacokinetic parameter AUC of dolutegravir	Change in dolutegravir AUC when dosed with standard, medium, high dose rifampicin	Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment
Secondary	Change in pharmacokinetic parameter Cmax of dolutegravir	Change in dolutegravir Cmax when dosed with standard, medium, high dose rifampicin	Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment
Secondary	Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)	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