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

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

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 Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: 3-in-1 tablet (EFV 400mg, TDF 300mg, 3TC 300mg)

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 82445
    • E-DA Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combined tablet (EFV 400,TDF 300, 3TC 300); 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.	Drug: 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.; Other Names: non applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C12 EFV concentration	The proportion of subjects achieving C12 EFV concentration >1.0 mg/L at Week 4.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-1 RNA load	The proportion of subjects with undetectable plasma HIV-1 RNA load (<50 copies/mL) at Week 12	Week 12
HIV-1 RNA load	The proportion of subjects with undetectable plasma HIV-1 RNA load (<50 copies/mL) at Week 24	Week 24
EFV concentration	The mean changes from baseline in C12 EFV concentration at Week 4.	Week 4
CD4+ T cell count	The mean changes from baseline in CD4+ T cell count at Week 12.	Week 12
CD4+ T cell count	The mean changes from baseline in CD4+ T cell count at Week 24.	Week 24

Collaborators and Investigators

• Sponsor: Yu-Jay Corp.
• Investigators: Principal Investigator: Hsin-Yun Sun, MD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Actual): March 6, 2019
• Study Completion (Actual): July 16, 2019

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 23, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Efavirenz; HIV Infections
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: YJ14001-COMBO-201801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No