Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin (DoRIS)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis; Hiv
• Intervention / Treatment: Drug: Dolutegravir

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Africa
  • Cape Town, South Africa
    • Desmond Tutu Health Foundation
• Uganda
  • Kampala, Uganda
    • Infectious Diseases Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dolutegravir	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Helen Reynolds
• Collaborators: Desmond Tutu HIV Centre; Infectious Disease Institute, Kampala, Uganda
• Investigators: Principal Investigator: Saye Khoo, University of Liverpool

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir
• Other Study ID Numbers: UoL001452

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No