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NCT04689737

Removal of Doravirine by Hemodialysis in HIV-Infected Patients With End-stage Renal Disease (ESRD)

Completed Phase 4 Results posted Last updated 27 August 2024
What this trial tests

Phase 4 trial testing Doravirine in HIV-infected Participants With ESRD Undergoing Routine Hemodialysis in 8 participants. Completed in 14 June 2021.

Timeline
20 March 2021
Primary endpoint
14 June 2021
14 June 2021

Quick facts

Lead sponsorFundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeother
Enrollment8
Start date20 March 2021
Primary completion14 June 2021
Estimated completion14 June 2021
Sites3 locations across Spain

Drugs / interventions tested

Conditions studied

Sponsor

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia — full company profile →

Who can join

Adults 18 to 99, any sex, with HIV-infected Participants With ESRD Undergoing Routine Hemodialysis. 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.

Percentatge of Doravirine Dialysis Extraction Ratio (ER) Primary · At day 6

The haemodialysis extraction ratio (ER) for doravirine was calculated as: ER(%) = ((Cin - Cout)/ Cin) × 100 where Cin is the pre-dialyser doravirine concentration (i.e. blood entering the dialyser) and Cout is the post-dialyser doravirine concentration (i.e. blood leaving the dialyser). Post-dialyser doravirine concentrations (Cout) were corrected for haemoconcentration by a factor F based on total protein (TP) concentration pre- and post-dialyser: F = TPin / TPout.

GroupValue95% CI
Experimental Group34.325.8 – 41.4
Percentage of Participants Developing Related Adverse Events Grade 3-4 Related to Doravirine Secondary · Baseline to day 20

Percentage of participants developing related adverse events grade 3 or grade 4 related to doravirine. Defining Grade 3 (severe) as symptoms causing inability to perform usual social and functional activities and Grade 4 (potentially life-threatening)as Symptoms causing inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.

GroupValue95% CI
Experimental Group2
Doravirine Concentration (mg/dl) Secondary · At day 6

Doravirine Concentration (mg/dl) in plasma at the end of the haemodialysis session.

GroupValue95% CI
Experimental Group785101 – 1851

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 to Day 20. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experimental Group
Serious: 2/8 (25%)
Deaths: 0/8

Serious adverse events (2 terms)

ReactionSystemExperimental Group
IQ-RCFI EM Hospitalization for Fibula FractureSurgical and medical procedures
Cardiac insufficiencyCardiac disorders
Other adverse events (2 terms — click to expand)

ReactionSystemExperimental Group
VomitingGastrointestinal disorders
HeadacheGeneral disorders

Most-reported serious reactions: IQ-RCFI EM Hospitalization for Fibula Fracture, Cardiac insufficiency.

Data from ClinicalTrials.gov NCT04689737 adverse events section.

Sponsor's own description

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with HIV infection in phase III clinical trials. Doravirine achieved non- inferiority when compared with efavirenz- and darunavir/ritonavir-based regimens. Doravirine is mainly metabolized and eliminated by the liver, with only 6% of the drug being excreted unchanged through the urine.In a study comparing 8 subjects with severe renal disease to 8 subjects without renal impairment, the single dose exposure of doravirine was 43% higher in subjects with severe renal function impairment.However, according to prescribing information, no dosage adjustment of doravirine is required in patients with mild, moderate, or severe renal impairment. On the other hand, data on doravirine pharmacokinetics in patients with ESRD on dialysis are lacking. This may be of special interest because doravirine has a relatively low molecular weight and it is only 76% bound to proteins in plasma. These characteristics could make possible for hemodialysis to remove doravirine from plasma, potentially leading to subtherapeutic concentrations of doravirine after the dialysis sessions. On the contrary, doravirine volume of distribution is about 60 liters,15 what could limit extraction of doravirine by hemodialysis. Since data on doravirine pharmacokinetics in PLWH with ESRD on dialysis are lacking, our aim is to evaluate the effect of intermittent hemodialysis on doravirine concentrations in HIV-infected patients with ESRD

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Removal of doravirine by haemodialysis in people living with HIV with end-stage renal disease.
    Moltó J, Graterol F, Curran A, Ramos N, et al · · 2022 · cited 5× · PMID 35425985 · DOI 10.1093/jac/dkac126

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing