Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

Study Overview
=================
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.

Official Title
-----------------
Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

Conditions
-----------------
Hiv, Tuberculosis

Intervention / Treatment
-----------------
* Drug: Dolutegravir


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dolutegravir<br> | Drug: Dolutegravir<br>* Dosed at 50 mg bd on 3 separate occasions with low, medium and high doses of rifampicin. Dosed at 50 mg od without rifampicin.<br>|

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 |