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NCT04272242

Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals

Terminated Phase 2 Results posted Last updated 19 September 2024
What this trial tests

Phase 2 trial testing Dolutegravir (DTG) in HIV Infection in 37 participants. Terminated before completion.

Timeline
27 February 2021
Primary endpoint
15 December 2021
27 December 2021

Quick facts

Lead sponsorNational Institute of Allergy and Infectious Diseases (NIAID)
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment37
Start date27 February 2021
Primary completion15 December 2021
Estimated completion27 December 2021
Sites10 locations across Zimbabwe, Haiti, South Africa, Malawi, Botswana, Thailand, United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 65, any sex, with HIV Infection or LTBI. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day Primary · Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28

This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmax defines the model-predicted maximum concentration observed over the 12- or 24- hours of the DTG dosing interval.

Day 0
GroupValue95% CI
Arm 1: DTG + INH + RPT4180.83920.6 – 5196.4
Day 28
GroupValue95% CI
Arm 1: DTG + INH + RPT3913.53475.7 – 4743.1
DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 1 by Visit Day Primary · Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28

This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model. For Arm 1, Day 28 (BID dosing), participant-specific AUC0-24h was estimated by summing participant-specific estimated AUC values for the 0-12 hour dosing interval (AUC0-12).

Day 0
GroupValue95% CI
Arm 1: DTG + INH + RPT68079.559139.5 – 85561.0
Day 28
GroupValue95% CI
Arm 1: DTG + INH + RPT65261.356748.6 – 81999.4
DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day Primary · Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28

This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmin defines the model-predicted minimum concentration observed over the 12- or 24- hour DTG dosing interval.

Day 0
GroupValue95% CI
Arm 1: DTG + INH + RPT1726.11267.9 – 2395.6
Day 28
GroupValue95% CI
Arm 1: DTG + INH + RPT1717.51206.6 – 2502.7
DTG PK Parameter Ctrough Determined Based on DTG Levels From Individual Participants in Arm 1 at Day 28 Primary · Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at day 28

This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 1 at day 28 (DTG BID with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 12- hour DTG dosing interval.

GroupValue95% CI
Arm 1: DTG + INH + RPT1987.01331.0 – 2377.5
Percentage of Participants in Arm 1 With an Occurrence of Grade 2 or Higher Adverse Event Secondary · From initiation of study treatment to day 28

Arm 1 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants were counted once at the highest grade.

Grade 2 Adverse Event
GroupValue95% CI
Arm 1: DTG + INH + RPT3621 – 54
Grade 3 Adverse Event
GroupValue95% CI
Arm 1: DTG + INH + RPT61 – 19
Percentage of Participants in Arm 1 Who Completed the Study Secondary · From initiation of study to day 28

Percentage of participants in Arm 1 who completed the study

GroupValue95% CI
Arm 1: DTG + INH + RPT8974 – 97
Percentage of Participants in Arm 1 Who Completed Study Drug Treatment Secondary · From initiation of study treatment to day 28

Percentage of participants in Arm 1 who completed study drug treatment (DTG+1HP)

GroupValue95% CI
Arm 1: DTG + INH + RPT9278 – 98
Percentage of Participants in Arm 1 With HIV-1 RNA Levels >50 Copies/mL Secondary · Measured at Days 28 and 42

This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels \>50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment).

Percentage with HIV-1 RNA >50 copies/mL at day 28
GroupValue95% CI
Arm 1: DTG + INH + RPT3
Percentage with HIV-1 RNA >50 copies/mL at day 42
GroupValue95% CI
Arm 1: DTG + INH + RPT0

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study treatment to study completion at Day 49 or premature study discontinuation.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1: DTG + INH + RPT
Serious: 0/36 (0%)
Deaths: 0/36
Other adverse events (17 terms — click to expand)

ReactionSystemArm 1: DTG + INH + RPT
NeutropeniaBlood and lymphatic system disorders
Blood creatinine increasedInvestigations
HeadacheNervous system disorders
LeukopeniaBlood and lymphatic system disorders
Conjunctivitis allergicEye disorders
PyrexiaGeneral disorders
COVID-19Infections and infestations
OrchitisInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
Glomerular filtration rate decreasedInvestigations
Weight decreasedInvestigations
White blood cell count decreasedInvestigations
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
UrticariaSkin and subcutaneous tissue disorders
HypertensionVascular disorders

Data from ClinicalTrials.gov NCT04272242 adverse events section.

Sponsor's own description

This study evaluated the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT was given with isoniazid (INH) daily for 4 weeks (1HP) as part of treatment for latent TB infection (LTBI) in HIV-1 and LTBI co-infected individuals.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Clinical standards for the diagnosis, treatment and prevention of TB infection.
    Migliori GB, Wu SJ, Matteelli A, Zenner D, et al · · 2022 · cited 55× · PMID 35197159 · DOI 10.5588/ijtld.21.0753
  2. Use of integrase inhibitors in HIV-associated tuberculosis in high-burden settings: implementation challenges and research gaps.
    Naidoo A, Naidoo K, Padayatchi N, Dooley KE. · · 2022 · cited 11× · PMID 35120633 · DOI 10.1016/s2352-3018(21)00324-6
  3. Twice-Daily Dolutegravir-Based Antiretroviral Therapy With 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis Prevention.
    Podany AT, Cramer Y, Imperial M, Rosenkranz SL, et al · · 2024 · cited 7× · PMID 38568956 · DOI 10.1093/cid/ciae183
  4. Are We There Yet? Short-Course Regimens in TB and HIV: From Prevention to Treatment of Latent to XDR TB.
    Ignatius EH, Swindells S. · · 2020 · cited 6× · PMID 32918195 · DOI 10.1007/s11904-020-00529-8
  5. Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine.
    Podany AT, Pham M, Sizemore E, Martinson N, et al · · 2022 · cited 3× · PMID 34918028 · DOI 10.1093/cid/ciab1037

Verify or expand the search:

Other trials of Dolutegravir (DTG)

Trials testing the same drug.

Other recruiting trials for HIV Infection

Currently open trials in the same condition.

Other National Institute of Allergy and Infectious Diseases (NIAID) trials

Trials by the same sponsor.

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