Atripla to Raltegravir Switch Study for CNS Toxicity
Information source: St Stephens Aids Trust
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infection
Intervention: Truvada/Raltegravir (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: St Stephens Aids Trust Official(s) and/or principal investigator(s): Mark Nelson, Dr, Principal Investigator, Affiliation: St Stephen's AIDS Trust
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.
Clinical Details
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 design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 4 Weeks on Treatment
Secondary outcome: The Rate of Neuropsychiatric and Central Nervous System (CNS) Toxicity of Raltegravir Therapy After 12 Weeks on TreatmentChange From Baseline to Week 12 in CD4+ Count After 12 Weeks of Raltegravir 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 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 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)
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
St Stephen's Centre, London SW10 9NH, United Kingdom
Additional Information
Starting date: October 2010
Last updated: November 13, 2014
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