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

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT01335620
• Collaborator: (none)
• Enrollment: 19
• Locations: 2
• Arm: 1
• Actual Duration (Months): 20
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: Raltegravir; Drug: Tenofovir; Drug: Emtricitabine	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: HIV affected over 60 years oldHIV affected over 60 years old
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study to Investigate the Safety, Pharmacokinetic Profile and Efficacy of Raltegravir in HIV-infected Patients at Least 60 Years of Age
• Actual Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Drug Levels in Blood [Day 28]

   rategravir concentration

2. Changes in Haematology, Biochemistry and Virology Tests [6 months]

   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

Secondary Outcome Measures

1. Cardiovascular Disease Markers [6 months]

   • To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir.

2. Cerebral Function; Changes in Global Cognitive Z-score [6 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chelsea & Westminster Hospital NHS Trust	London		United Kingdom	SW10 9TH
2	Imperial College Healthcare NHS Trust	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Imperial College London

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT01335620
• Other Study ID Numbers: RTG_60; 2010-022907-23
• First Posted: Apr 14, 2011
• Last Update Posted: Nov 20, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: HIV; Pharmatokinetic; 60 years old; Raltegravir
• Additional relevant MeSH terms: Tenofovir; Emtricitabine; Raltegravir Potassium

Study Results

Participant Flow

Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (3.4)
Sex: Female, Male (Count of Participants)
Female	1 5.3%
Male	18 94.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 15.8%
White	16 84.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	19 100%

Outcome Measures

1. Primary Outcome

Title	Drug Levels in Blood
Description	rategravir concentration
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
Measure Participants	19
Geometric Mean (95% Confidence Interval) [ng/ml]	1732

2. Primary Outcome

Title	Changes in Haematology, Biochemistry and Virology Tests
Description	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
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

No data collected

Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
Measure Participants	0

3. Secondary Outcome

Title	Cardiovascular Disease Markers
Description	• To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

No data collected

Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
Measure Participants	0

4. Secondary Outcome

Title	Cerebral Function; Changes in Global Cognitive Z-score
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
Measure Participants	19
Mean (Standard Deviation) [score on a scale]	0.91 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Truvada Plus Raltegravir
	Comments	Compare baseline to 24 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Regression, Logistic
	Comments

Adverse Events

Time Frame	1 year
Arm/Group Title	Truvada Plus Raltegravir
Arm/Group Description	Single arm study Raltegravir: 400 mg twice daily
All Cause Mortality
	Truvada Plus Raltegravir
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Serious Adverse Events
	Truvada Plus Raltegravir
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Other (Not Including Serious) Adverse Events
	Truvada Plus Raltegravir
	Affected / at Risk (%)	# Events
Total	0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.