Efavirenz to Dolutegravir Switch in Patients With CNS Toxicity

NCT02285374 | Unknown Phase 4

• 1 other identifier: SSAT 056
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase IV, open label, multicentre trial that will be taking place at 4 sites in the United Kingdom (UK). Efavirenz which is taken in combination with Kivexa® or as part of the combination pill, Atripla® is a recommended firstline regimen for the treatment of Human Immunodeficiency Virus-1 (HIV- 1) infection. Treatment against the HIV virus is also referred to as antiretroviral therapy. Toxicity is the most common reason for modification of firstline therapy. Central Nervous System (CNS) side effects such as difficulty with sleeping \& bad dreams are common side effect of Efavirenz based therapy and is one of the most frequent reasons for switching or discontinuing highly active antiretroviral therapy. Dolutegravir is within a novel class of antiretroviral agents licensed in the UK for the treatment of HIV. In combination with Truvada®, it showed fewer side effects when compared to Efavirenz in other clinical studies, where patients were starting HIV treatment for the first time, or switching from other agents. The purpose of the study is to investigate the benefits of switching away from Eefavirenz (in combination with Kivexa® or as part of the combination pill, Atripla®) to Dolutegravir in patients with CNS side effects (such as difficulty with sleeping, bad dreams etc).

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Rate of neuropsychiatric and central nervous system (CNS) toxicity

  The rate of neuropsychiatric and central nervous system (CNS) toxicity (as measured by a questionnaire based on EFV Summary of Product Characteristics (SPC) and graded based on the ACTG adverse event scale) after 4 weeks of dual N(t)RTI plus DTG therapy: * Sum total of all grades of CNS adverse events * Median number of AIDS Clinical Trial Group (ACTG) grade 2-3 CNS adverse events Results 4 weeks post switch for each arm will be compared with baseline results and week 4 results will be compared between arms (ie 4 weeks post switch for arm 1 and day of switch for arm 2.).

  4 weeks post switch, day1

Secondary Outcomes (15)

• Rate of neuropsychiatric and central nervous system (CNS) toxicity

  12 weeks post switch, day1

• Virologic suppression

  4 and 12 weeks post switch, day1

• CD4 cell count and %

  4 and 12 weeks post switch, day1

• Quality of life

  4 and 12 weeks post switch, day1

• CNS toxicity

  4 and 12 weeks post switch, day1

Study Arms (2)

Arm 1

EXPERIMENTAL

Truvada (tenofovir 245mg/emtricitabine 200mg) or Kivexa (abacavir 600mg/lamivudine 300mg) one tablet once daily plus Dolutegravir 50mg (one tablet) once daily

Drug: Dolutegravir, efavirenz, efavirenz/emtricitabine/tenofovir

Arm 2

EXPERIMENTAL

Atripla (efavirenz 600mg, emtricitabine 200mg, tenofovir 245mg) one tablet once daily, or Truvada (tenofovir 245mg/emtricitabine 200mg) or Kivexa (abacavir 600mg/lamivudine 300mg) one tablet once daily plus efavirenz 600mg one tablet once daily for 4 weeks. At week 4, efavirenz is switched to Dolutegravir 50mg (one tablet) once daily

Drug: Dolutegravir, efavirenz, efavirenz/emtricitabine/tenofovir

Interventions

Dolutegravir, efavirenz, efavirenz/emtricitabine/tenofovir DRUG

Arm 1: Switch efavirenz to dolutegravir immediately (at baseline) for 12 weeks Arm 2: Continue on pre-study regimen (unchanged) for 4 weeks and then switch efavirenz to dolutegravir for 12 weeks

Also known as: Tivicay®, efavirenz, Atripla®

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is male or female aged 18 years or older
• Has HIV-1 infection documented in their medical notes
• Has signed the Informed Consent Form voluntarily
• Is willing to comply with the protocol requirements
• Is currently on an antiretroviral regimen comprising at least three licensed antiretroviral agents one of which is EFV, for at least 12 weeks
• No previous exposure to integrase inhibitors
• Has an HIV-plasma viral load at screening \<400 copies/mL (single re-test allowed)
• Has a CD4 cell count at screening \>50 cells/mm3
• Estimated glomerular filtration rate (MDRD) \>50 ml/min.
• Has symptomatic CNS related toxicity associated with EFV at least Grade 2 by ACTG criteria
• If female and of childbearing potential, is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial.

You may not qualify if:

• Infected with HIV-2
• Using any concomitant therapy disallowed as per SPC for the study drugs
• Has acute viral hepatitis including, but not limited to, A, B, or C
• Subjects positive for Hepatitis B at screening (+HBsAg), or anticipated need for Hepatitis C virus (HCV) therapy during the study
• Alanine aminotransferase (ALT) greater than or equal to 5 times the upper limit of normal (ULN), OR ALT greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with \>35% direct bilirubin)
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Any investigational drug within 30 days prior to the trial drug administration
• Has received dolutegravir in the past
• Any clinical evidence of baseline resistance mutations
• History or presence of allergy to DTG or excipients (D-Mannitol, Microcystalline Cellulose, Povidone, Croscarmellose Sodium, Sodium Stearyl Fumarate, Talc, white film coat)
• Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification
• Moderate or severe renal impairment (creatinine clearance \< 50ml/min by Cockroft-Gault method)
• If female, she is pregnant or breastfeeding
• Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
• Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.

Sponsors & Collaborators

• St Stephens Aids Trust: lead
• ViiV Healthcare: collaborator

Study Sites (1)

Chelsea and Westminster Hospital

London, SW10 9TH, United Kingdom

Location

MeSH Terms

Interventions

dolutegravir; efavirenz; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Oxazines

Study Officials

• Mark Nelson, MD

  St Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nuno Morgado

CONTACT

+44 (0)20 3315 3765; nuno.morgado@chelwest.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: November 7, 2014
• Study Start: November 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: December 1, 2015
• Last Updated: November 7, 2014

Record last verified: 2014-10

Locations

GB (1)