SSAT058: Atripla to Eviplera Switch in Patients Without Central Nervous System Symptoms

NCT02529059 | Completed Phase 4

• 1 other identifier: SSAT058
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

This study aims to investigate whether substitution of Efavirenz (EFV) as the Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) fixed-dose combination (FDC) Atripla, with Rilpivirine as the tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) fixed-dose combination (FDC) Eviplera, leads to resolution of covert Central Nervous System (CNS) toxicity associated with EFV, continued virological suppression and immunological reconstitution and whether this is associated with an improvement in quality of life, sleep, anxiety/depression and neurocognitive function; the impact of switch on adherence will also be investigated.

Conditions

HIV

Outcome Measures

Primary Outcomes (4)

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the proportion of patients experiencing grade 2-4 neuropsychiatric and CNS toxicity

  As defined by the ACTG Adverse event scale and collected by CNS questionnaire.

  4 Weeks compared to baseline

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the median number of grade 2-4 neuropsychiatric and CNS toxicity

  As defined by the ACTG adverse event scale and collected by CNS questionnaire.

  4 Weeks compared to baseline

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the median CNS score.

  Derived from the sum of toxicity of all grades collected in the CNS questionnaire.

  4 Weeks compared to baseline

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the change in sleep score using the Pittsburgh Sleep Questionnaire.

  4 Weeks compared to baseline

Secondary Outcomes (15)

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 & 24 weeks compared to baseline, as measured by proportion of patients experiencing grade 2-4 neuropsychiatric and CNS toxicity.

  12 and 24 weeks compared to baseline

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by the median number of grade 2-4 neuropsychiatric and CNS toxicity.

  12 and 24 weeks compared to baseline

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by the median CNS score

  12 and 24 weeks compared to baseline

• Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by change in sleep score using the Pittsburgh Sleep Questionnaire.

  12 and 24 weeks compared to baseline

• Change in neuropsychiatric and CNS parameters as measured by the change in the Hospital Anxiety and Depression Scale (HADS) at 4, 12 and 24 weeks as compared with baseline.

  4, 12 and 24 weeks compared to baseline

Study Arms (1)

Switch from Atripla to Eviplera

EXPERIMENTAL

Drug: Eviplera

Interventions

Eviplera DRUG

A single-pill fixed dose combination of tenofovir 245mg, emtricitabine 200mg and rilpivirine 25mg once daily for 24 weeks.

Also known as: Rilpivirine, tenofovir, emtricitabine

Switch from Atripla to Eviplera

Eligibility Criteria

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

You may qualify if:

• Patient volunteers who meet all of the following criteria are eligible for this trial:
• Is male or female aged 18 years or above
• Has HIV-1 infection documented in their medical notes
• Has signed the Informed Consent Form voluntarily
• Is willing to comply with the protocol requirements
• Has been on Atripla for at least 12 weeks before enrolment
• Has an undetectable HIV-plasma viral load at screening by local assay (single re-test allowed)
• Has a CD4 cell count at screening \>50 cells/mm3
• Has an estimated glomerular filtration rate (MDRD) \>50 ml/min.
• Has no significant CNS symptoms which may be attributable to EFV.
• If female and of childbearing potential, is using effective birth control methods (for example, hormonal contraceptive, condom, abstinence, IUD, 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. Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
• If a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit

You may not qualify if:

• Patients meeting 1 or more of the following criteria cannot be selected:
• Infected with HIV-2
• Using any concomitant therapy disallowed as per SPC for the study drugs (e.g proton pump inhibitors )
• Has acute viral hepatitis including, but not limited to, A, B, or C
• Has chronic hepatitis B and/or C with AST and/or ALT \>5 x ULN Note: Patients can enter trial with chronic HBV if HBV-DNA undetectable at screen (and no detectable result in last 6 months) and with chronic HCV if not expected to require treatment during the trial period.
• Any investigational drug within 30 days prior to the trial drug administration
• Has ever received rilpivirine in the past
• Any clinical evidence of baseline resistance mutations, prior to commencing antiretroviral therapy.
• Known allergy to lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
• Severe hepatic impairment (defined as Child-Pugh-Turcotte (CPT) Score C).
• 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.
• If participating in the MR Imaging substudy, any contraindications to magnetic resonance scanning according to local radiology guidelines (to be assessed by MR Spectroscopy Imaging Department)

Sponsors & Collaborators

• St Stephens Aids Trust: lead
• Gilead Sciences: collaborator

Study Sites (3)

Brighton & Sussex University Hospitals Nhs Trust

Brighton, United Kingdom

Location

St. Mary's Hospital

London, United Kingdom

Location

St. Stephen's Centre

London, United Kingdom

Location

MeSH Terms

Interventions

Rilpivirine; Tenofovir; Emtricitabine

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mark Nelson

  St Stephen's AIDs Trust

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: August 19, 2015
• Study Start: November 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: September 18, 2017

Record last verified: 2017-09

Locations

GB (3)