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Therapeutic Drug Monitoring Study of Reduced-Dose Efavirenz (400 mg) in Combo Tablet for Patients Receiving Atripla With Viral Suppression in Taiwan

Phase 3
Completed
Conditions
HIV Infections
Interventions
Drug: 3-in-1 tablet (EFV 400mg, TDF 300mg, 3TC 300mg)
Registration Number
NCT03595709
Lead Sponsor
Yu-Jay Corp.
Brief Summary

Prospective, Therapeutic Drug Monitoring Study of Reduced-Dose Efavirenz (400 mg) Plus Tenofovir Disoproxil Fumarate (TDF) and Lamivudine in a Fixed-Dose Combination Tablet (Combo) for Patients Receiving Co-Formulated TDF, Emtricitabine and Efavirenz (Atripla) with Viral Suppression in Taiwan

Detailed Description

Efavirenz (EFV) is the most widely used non-nucleoside reverse transcriptase inhibitor (NNRTI). The recommended dose of EFV is 600 mg daily; however, a phase II study showed no significant difference in viral suppression rates across the different EFV groups (200 mg, 400 mg, and 600 mg) at 24 weeks. The week 96 analysis of ENCORE 1 study confirmed the durable virological non-inferiority of EFV 400 mg to the standard 600 mg dose when given as initial therapy with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Fewer EFV-related adverse events (AEs) and fewer treatment discontinuations were also observed in the reduced dose group. The efficacy and safety findings provide robust evidence to redefine the EFV dose for HIV treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
Inclusion Criteria
  • Patients who are receiving co-formulated TDF/ FTC/ EFV (600 mg) and have achieved an undetectable plasma viral load (<50 copies/mL) for 6 months or longer at screening visit.
  • Having C12 EFV of 1 mg/L or greater at screening.
  • (C12 EFV will be determined by using blood sample collected 12 ± 1 hour after previous dosing of co-formulated TDF/ FTC/ EFV (600 mg).
  • No known treatment failure to regimens containing TDF, 3TC or FTC, plus EFV.
  • Infected with HIV harboring no known resistance-associated mutations to EFV, TDF, 3TC or FTC.
  • No known allergies to EFV, TDF, 3TC or FTC.
  • Aged ≧20 years.
  • Calculated creatinine clearance (ClCr) ≥ 50 mL/min (Cockcroft-Gault formula).
  • Provision of written informed consent.
Exclusion Criteria
  • The following laboratory values:

    • Absolute neutrophil count (ANC) <500 cells/μL
    • Hemoglobin <7.0 g/dL
    • Platelet count <50,000 cells/μL
    • Serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >5x upper limit of normal (ULN)
  • Pregnant women or nursing mothers.

  • Active opportunistic or malignant disease not under adequate control.

  • Use of immunomodulators within 30 days prior to screening visit.

  • Use any of the prohibited medications: bepridil, astemizole, terfenadine, dihydroergotamine, ergometrine, ergotamine, systemic cytotoxic chemotherapy, amodiaquine, pimozide, midazolam, triazolam, cisapride、St John's Wort、 Elbasvir/Grazoprevir and Simeprevir.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
combined tablet (EFV 400,TDF 300, 3TC 300)3-in-1 tablet (EFV 400mg, TDF 300mg, 3TC 300mg)All eligible subjects will receive 3-in-1 tablet (EFV 400mg, TDF 300mg, 3TC 300mg) once daily for 24 weeks orally on empty stomach before bedtime. If the event of toxicity or tolerability issues requires a change from study drug, switching to the best available treatment will be recommended.
Primary Outcome Measures
NameTimeMethod
C12 EFV concentrationWeek 4

The proportion of subjects achieving C12 EFV concentration \>1.0 mg/L at Week 4.

Secondary Outcome Measures
NameTimeMethod
EFV concentrationWeek 4

The mean changes from baseline in C12 EFV concentration at Week 4.

HIV-1 RNA loadWeek 24

The proportion of subjects with undetectable plasma HIV-1 RNA load (\<50 copies/mL) at Week 24

CD4+ T cell countWeek 24

The mean changes from baseline in CD4+ T cell count at Week 24.

Trial Locations

Locations (2)

E-Da Hospital

🇨🇳

Kaohsiung, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

E-Da Hospital
🇨🇳Kaohsiung, Taiwan

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