Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

NCT04166474 | Completed Phase 4 DMC

• 1 other identifier: UoL001452
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hiv; Tuberculosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in pharmacokinetic parameter AUC of dolutegravir

  Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment

• Change in pharmacokinetic parameter Cmax of dolutegravir

  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)

  From first dose of dolutegravir until study completion approximately 2 years

Study Arms (1)

Dolutegravir

EXPERIMENTAL

Drug: Dolutegravir

Interventions

Dolutegravir DRUG

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

Dolutegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \< 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)

Sponsors & Collaborators

• Helen Reynolds: lead
• Infectious Disease Institute, Kampala, Uganda: collaborator
• Desmond Tutu HIV Centre: collaborator

Study Sites (2)

Desmond Tutu Health Foundation

Cape Town, South Africa

Location

Infectious Diseases Institute

Kampala, Uganda

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Tuberculosis

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

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

Study Officials

• Saye Khoo

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Programme manager

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 18, 2019
• Study Start: November 18, 2021
• Primary Completion: February 7, 2024
• Study Completion: February 7, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1); ZA (1)