Clinical trial NCT03595709: Therapeutic Drug Monitoring Study of Reduced-Dose Efavirenz (400 mg) in Combo Tablet for Patients Receiving Atripla With Viral Suppression in Taiwan
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Efavirenz
HIV Infections
Lead sponsor: Yu-Jay Corp.
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, open-label
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: C12 EFV concentration
timeFrame: Week 4
Secondary outcomes:
measure: HIV-1 RNA load
timeFrame: Week 12
measure: HIV-1 RNA load
timeFrame: Week 24
measure: EFV concentration
timeFrame: Week 4
measure: CD4+ T cell count
timeFrame: Week 12
measure: CD4+ T cell count
timeFrame: Week 24
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Hsin-Yun Sun, MD
role: PRINCIPAL_INVESTIGATOR
References: