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Atripla to Raltegravir Switch Study for CNS Toxicity (SSAT036)

Primary Purpose

HIV Infection

Status
Completed
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Truvada/Raltegravir
Sponsored by
St Stephens Aids Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. is male or female aged 18 years or above
  2. has a documented HIV-1 infection
  3. has signed the Informed Consent Form voluntarily
  4. is willing to comply with the protocol requirements
  5. has an HIV-plasma viral load at screening <50 copies/mL
  6. has a CD4 cell count at Screening >50 cells/mm3
  7. 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
  8. estimated glomerular filtration rate (by MDRD or CG methods) >50 ml/min.
  9. has symptomatic toxicity associated with EFV after at least 12 weeks of therapy
  10. 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
  11. 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

Exclusion Criteria:

  1. is infected with HIV-2
  2. is using any concomitant therapy disallowed as per SPC for the study drugs (section 5.2)
  3. 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
  4. has acute viral hepatitis including, but not limited to, A, B, or C
  5. 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.
  6. has received any investigational drug within 30 days prior to the trial drug administration
  7. Prior exposure to raltegravir or investigational integrase inhibitors
  8. Any tenofovir or emtricitabine associated resistance mutations
  9. No baseline resistance test available
  10. Clinically significant allergy or hypersensitivity to any trial medication excipients
  11. If female, she is pregnant or breastfeeding
  12. 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).
  13. Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR > 1.5 or albumin < 30g/L or bilirubin > 2.5 x ULN
  14. Resolution of their CNS toxicity between Screening and Baseline visits
  15. Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.

Sites / Locations

  • St Stephen's Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All Subjects Truvada/Raltegravir

Arm Description

All Subjects will receive the same intervention, Truvada/Raltegravir

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 12 Weeks on Treatment
The rate of neuropsychiatric and central nervous system (CNS) toxicity as measured after 12 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)
Change From Baseline to Week 12 in CD4+ Count After 12 Weeks of Raltegravir
Change from baseline to week 12 in CD4+ count after 12 weeks of raltegravir having switched from efavirenz-containing therapy
Proportion of Patients With Viral Load < 50 Copies/mL and <400 Copies/ml at Weeks 4 and 12 After Switching to Raltegravir
To assess the proportion of patients with viral load < 50 copies/mL and <400 copies/ml at weeks 4 and 12 after switching to raltegravir
Change in Fasting Lipids (Total Cholesterol and Subfractions and Triglycerides) After 4 and 12 Weeks of Raltegravir
To assess the change in fasting lipids (total cholesterol and subfractions and triglycerides) after 4 and 12 weeks of raltegravir
Proportion of Patients With Grade 2-4 Laboratory Parameters (Excluding Lipids) After 12 Weeks of Raltegravir Compared With Baseline
To assess the proportion of patients with grade 2-4 laboratory parameters (excluding lipids) after 12 weeks of raltegravir compared with baseline
Proportion of Patients With Grade 2-4 Non-CNS Adverse Events After 12 Weeks of Raltegravir Compared With Baseline
To assess the proportion of patients with grade 2-4 non-CNS adverse events after 12 weeks of raltegravir compared with baseline
Change From Baseline in Adherence From Baseline After 12 Weeks of Raltegravir as Measured by the Adherence Questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
To assess the change from baseline in adherence from baseline after 12 weeks of raltegravir as measured by the adherence questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
Change From Baseline of CNS Toxicity as Measured by Hospital Anxiety and Depression (HADS) Score (Baseline vs Week 12)
To assess the change from baseline of CNS toxicity as measured by Hospital Anxiety and Depression (HADS) score (baseline vs week 12)

Full Information

First Posted
September 3, 2010
Last Updated
November 13, 2014
Sponsor
St Stephens Aids Trust
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1. Study Identification

Unique Protocol Identification Number
NCT01195467
Brief Title
Atripla to Raltegravir Switch Study for CNS Toxicity
Acronym
SSAT036
Official Title
A Phase III, Open-label, Single Centre, Single-arm, Pilot Study to Assess the Feasibility of Switching, Individuals Receiving Efavirenz With Continuing Central Nervous System (CNS) Toxicity, to Raltegravir
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St Stephens Aids Trust

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
The majority of individuals who commence treatment for HIV in the UK start with a regimen that includes EFV in combination with other antiretrovirals. These regimens are convenient (once daily dosing) and highly efficacious. However EFV has several potential drawbacks including continued CNS toxicity, the potential for teratogenesis and a low barrier to the development of virological resistance. Clinically controlled trials frequently reported undesirable nervous system side effects in patients receiving 600 mg EFV with other antiretroviral agents, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. CNS symptoms of moderate to severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens. These symptoms were severe in 2.0% of patients receiving EFV 600 mg daily and in 1.3% of patients receiving control regimens. In clinical studies 2.1% of patients treated with 600 mg of EFV discontinued therapy because of nervous system symptoms The majority of individuals who commence treatment for HIV in the UK start with a regimen that includes EFV in combination with other antiretrovirals. These regimens are convenient (once daily dosing) and highly efficacious. However EFV has several potential drawbacks including continued CNS toxicity, the potential for teratogenesis and a low barrier to the development of virological resistance. Clinically controlled trials frequently reported undesirable nervous system side effects in patients receiving 600 mg EFV with other antiretroviral agents, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. CNS symptoms of moderate to severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens. These symptoms were severe in 2.0% of patients receiving EFV 600 mg daily and in 1.3% of patients receiving control regimens. In clinical studies 2.1% of patients treated with 600 mg of EFV discontinued therapy because of nervous system symptoms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All Subjects Truvada/Raltegravir
Arm Type
Experimental
Arm Description
All Subjects will receive the same intervention, Truvada/Raltegravir
Intervention Type
Drug
Intervention Name(s)
Truvada/Raltegravir
Other Intervention Name(s)
Truvada® = tenofovir + emtricitabine, Atripla® = tenofovir + emtricitabine + efavirenz, Raltegravir = isentress
Intervention Description
All subjects currently on Atripla® will switch to Truvada/Raltegravir
Primary Outcome Measure Information:
Title
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 4 Weeks on Treatment
Description
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)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 12 Weeks on Treatment
Description
The rate of neuropsychiatric and central nervous system (CNS) toxicity as measured after 12 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)
Time Frame
baseline to week 12
Title
Change From Baseline to Week 12 in CD4+ Count After 12 Weeks of Raltegravir
Description
Change from baseline to week 12 in CD4+ count after 12 weeks of raltegravir having switched from efavirenz-containing therapy
Time Frame
baseline to week 12
Title
Proportion of Patients With Viral Load < 50 Copies/mL and <400 Copies/ml at Weeks 4 and 12 After Switching to Raltegravir
Description
To assess the proportion of patients with viral load < 50 copies/mL and <400 copies/ml at weeks 4 and 12 after switching to raltegravir
Time Frame
week 4 to week 12
Title
Change in Fasting Lipids (Total Cholesterol and Subfractions and Triglycerides) After 4 and 12 Weeks of Raltegravir
Description
To assess the change in fasting lipids (total cholesterol and subfractions and triglycerides) after 4 and 12 weeks of raltegravir
Time Frame
week 4 to week 12
Title
Proportion of Patients With Grade 2-4 Laboratory Parameters (Excluding Lipids) After 12 Weeks of Raltegravir Compared With Baseline
Description
To assess the proportion of patients with grade 2-4 laboratory parameters (excluding lipids) after 12 weeks of raltegravir compared with baseline
Time Frame
baseline to week 12
Title
Proportion of Patients With Grade 2-4 Non-CNS Adverse Events After 12 Weeks of Raltegravir Compared With Baseline
Description
To assess the proportion of patients with grade 2-4 non-CNS adverse events after 12 weeks of raltegravir compared with baseline
Time Frame
baseline to week 12
Title
Change From Baseline in Adherence From Baseline After 12 Weeks of Raltegravir as Measured by the Adherence Questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
Description
To assess the change from baseline in adherence from baseline after 12 weeks of raltegravir as measured by the adherence questionnaire: Medication Adherence Self-Report Inventory (M-MASRI)
Time Frame
baseline to week 12
Title
Change From Baseline of CNS Toxicity as Measured by Hospital Anxiety and Depression (HADS) Score (Baseline vs Week 12)
Description
To assess the change from baseline of CNS toxicity as measured by Hospital Anxiety and Depression (HADS) score (baseline vs week 12)
Time Frame
baseline to week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Resolution of their CNS toxicity between Screening and Baseline visits Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Nelson, Dr
Organizational Affiliation
St Stephen's AIDS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Stephen's Centre
City
London
ZIP/Postal Code
SW10 9NH
Country
United Kingdom

12. IPD Sharing Statement

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Atripla to Raltegravir Switch Study for CNS Toxicity

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