The Safety, Pharmacokinetic Profile and Efficacy of Raltegravir in HIV-infected Patients at Least 60 Years of Age

An Open Label Study to Investigate the Safety, Pharmacokinetic Profile and Efficacy of Raltegravir in HIV-infected Patients at Least 60 Years of Age

This is a phase IV, open label, prospective, one phase pharmacokinetic and observational study.

Twenty HIV-1 infected subjects will be recruited, subjects will switch antiretroviral therapy to:

• tenofovir/emtricitabine 245/200 mg daily (Truvada™) plus
• raltegravir 400 mg twice daily On day 28, all subjects will attend for an intensive 24 hour pharmacokinetic visit.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Raltegravir; Drug: Tenofovir; Drug: Emtricitabine

Detailed Description

This is a phase IV, open label, prospective, one phase pharmacokinetic and observational study.

Twenty HIV-1 infected subjects will be recruited. Eligible subjects will currently be receiving stable antiretroviral therapy with undetectable plasma HIV RNA and have no evidence of previous HIV- resistance mutations on genotypic resistance testing.

At baseline, subjects will switch antiretroviral therapy to:

• tenofovir/emtricitabine 245/200 mg daily (Truvada™) plus
• raltegravir 400 mg twice daily On day 28, all subjects will attend for an intensive 24 hour pharmacokinetic visit.

Follow up over 6 months, subjects will attend on days 14, 90 and 180 for follow up visits that will include standard safety parameters. Assessment of cardiac biomarkers at baseline and on days 90 and 180 and assessment of neurocognitive function at screening, baseline and on day 180 will also be undertaken.

Following completion of this study, subjects will recommence their usual antiretroviral treatment regimen and attend for a study follow up visit.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, SW10 9TH
    • Chelsea & Westminster Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HIV-1 infected males or females
2. 60 years of age or greater*
3. signed informed consent
4. willing to switch therapy as per study protocol
5. no previous exposure to raltegravir or HIV-1 integrase inhibitors
6. plasma HIV RNA < 50 copies/mL at screening and on at least one other occasion over the last 3 months
7. currently receiving a stable antiretroviral regimen with no antiretroviral drug switches for at least 3 months
8. no previous clinically-significant resistance documented on HIV-1 genotypic resistance
9. subjects in good health upon medical history, physical exam, and laboratory testing
10. BMI above or equal to 18 and below 32
11. Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study.
12. Have local screening laboratory results (haematology and chemistry that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance * 50% of total enrolled cohort will be 65 years of age or over. Subsequent to 10 subjects aged between 60 and 64 recruited, only subjects aged 65 or over will be eligible.

Exclusion Criteria:

1. current alcohol abuse or drug dependence
2. positive urine drug of abuse screening
3. active opportunistic infection or significant co-morbidities
4. current disallowed concomitant medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tenofovir/Emtricitabine and Raltegravir; Single arm study tenofovir/emtricitabine 245/200 mg once daily and raltegravir 400 mg twice daily	Drug: Raltegravir; 400 mg twice daily; Other Names: Isentress; Drug: Tenofovir; 245 mg once daily; Drug: Emtricitabine; 200mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Levels in Blood	rategravir concentration	Day 28
Changes in Haematology, Biochemistry and Virology Tests	full blood count, electrolytes and blood lipids will be measured at all visits to assess for changes through out the study. HIV viral load will also be measured to assess the efficacy of the medication at controlling the virus	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Disease Markers	• To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir.	6 months
Cerebral Function; Changes in Global Cognitive Z-score	Cerebral function via cognitive testing before and after a switch in antiretroviral therapy to raltegravir. Mean Scores from the eight tasks (NPZ-8) assessed were used to derive a global composite measure of neurocognitive function. The result shows the change before and after switch, an increase in z-score represents an improvement in cognitive function assessed by CogState battery, required approximately 10-15 min for completion.	6 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Marta Boffito, Chelsea & Westminster Hospital; Principal Investigator: Alan Winston, MB BH, Imperial College London

Publications and helpful links

General Publications

• Vera JH, Jackson A, Dickinson L, Else L, Barber T, Mora-Peris B, Back D, Boffito M, Winston A. The pharmacokinetic profile of raltegravir-containing antiretroviral therapy in HIV-infected individuals over 60 years of age. HIV Clin Trials. 2015 Jan-Feb;16(1):39-42. doi: 10.1179/1528433614Z.0000000006. Epub 2015 Jan 14.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 25, 2011
• First Submitted That Met QC Criteria: April 13, 2011
• First Posted (Estimate): April 14, 2011

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: HIV; Raltegravir; Pharmatokinetic; 60 years old
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium
• Other Study ID Numbers: RTG_60; 2010-022907-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No