Atripla to Raltegravir Switch Study for CNS Toxicity

NCT01195467 | Completed Phase 3 Results

• 1 other identifier: SSAT 036
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate the benefits of switching away from efavirenz (part of the combination pill, Atripla®) in patients with central nervous system side effects (such as insomnia {difficulty with sleeping}, bad dreams etc). The investigators will investigate the effect of switching to Truvada (a combination pill of tenofovir and emtricitabine, the other two components of Atripla) plus raltegravir. Raltegravir is a licensed drug for HIV treatment which showed side effects were fewer in number when compared to efavirenz in 2 other clinical studies, where patients were starting HIV treatment for the first time. This study will also investigate the safety (in terms of other side effects and the routine blood tests which the investigators ordinarily use to monitor your treatment) and monitor effectiveness, your viral load and CD4 counts, when you switch treatment from Atripla® to Truvada/raltegravir.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 4 Weeks on Treatment

  To assess the rate of neuropsychiatric and central nervous system (CNS) toxicity as measured from baseline to 4 weeks of raltegravir therapy as measured by sleep questionnaire \& CNS toxicity (as determined by questionnaire based on efavirenz SPC and graded based on the ACTG adverse event scale)

  4 weeks

Secondary Outcomes (8)

• The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 12 Weeks on Treatment

  baseline to week 12

• Change From Baseline to Week 12 in CD4+ Count After 12 Weeks of Raltegravir

  baseline to week 12

• Proportion of Patients With Viral Load < 50 Copies/mL and <400 Copies/ml at Weeks 4 and 12 After Switching to Raltegravir

  week 4 to week 12

• Change in Fasting Lipids (Total Cholesterol and Subfractions and Triglycerides) After 4 and 12 Weeks of Raltegravir

  week 4 to week 12

• Proportion of Patients With Grade 2-4 Laboratory Parameters (Excluding Lipids) After 12 Weeks of Raltegravir Compared With Baseline

  baseline to week 12

Study Arms (1)

All Subjects Truvada/Raltegravir

EXPERIMENTAL

All Subjects will receive the same intervention, Truvada/Raltegravir

Drug: Truvada/Raltegravir

Interventions

Truvada/Raltegravir DRUG

All subjects currently on Atripla® will switch to Truvada/Raltegravir

Also known as: Truvada® = tenofovir + emtricitabine, Atripla® = tenofovir + emtricitabine + efavirenz, Raltegravir = isentress

All Subjects Truvada/Raltegravir

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 above
• has a documented HIV-1 infection
• has signed the Informed Consent Form voluntarily
• is willing to comply with the protocol requirements
• has an HIV-plasma viral load at screening \<50 copies/mL
• has a CD4 cell count at Screening \>50 cells/mm3
• has been on a stable ART, with at least 3 licensed agents, one of which being EFV, for at least 12 weeks at Screening, and has been on Atripla for at least 4 weeks at screening; the subject must be willing to stay on treatment until Baseline
• estimated glomerular filtration rate (by MDRD or CG methods) \>50 ml/min.
• has symptomatic toxicity associated with EFV after at least 12 weeks of therapy
• if female and of childbearing potential, she 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 (or after last intake of investigational ARVs); 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:

• is infected with HIV-2
• is using any concomitant therapy disallowed as per SPC for the study drugs (section 5.2)
• has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions (must be discussed with the sponsor prior to enrolment):
• Stable cutaneous Kaposi's Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period
• CD4 count less than 200 cells/mm3 Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed
• 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: Subjects co-infected with chronic HBV or HCV can enter the trial if clinically stable and not expected to require treatment during the trial period.
• has received any investigational drug within 30 days prior to the trial drug administration
• Prior exposure to raltegravir or investigational integrase inhibitors
• Any tenofovir or emtricitabine associated resistance mutations
• No baseline resistance test available
• Clinically significant allergy or hypersensitivity to any trial medication excipients
• If female, she is pregnant or breastfeeding
• screening blood results 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).
• Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR \> 1.5 or albumin \< 30g/L or bilirubin \> 2.5 x ULN

Sponsors & Collaborators

• St Stephens Aids Trust: lead

Study Sites (1)

St Stephen's Centre

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Raltegravir Potassium; Emtricitabine; efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; 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; Pyrrolidinones; Pyrrolidines

Results Point of Contact

• Title: Dr Mark Nelson
• Organization: St Stephen's AIDS Trust

mark.nelson@chelwest.nhs.uk

02033

Study Officials

• Mark Nelson, Dr

  St Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 6, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 26, 2014
• Results First Posted: November 4, 2014

Record last verified: 2014-11

Locations

GB (1)