FindTrial
Sign In

A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies (0518-019)

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK-0518 in Combination With an Optimized Background Therapy (OBT), Versus Optimized Background Therapy Alone, in HIV-Infected Patients With Documented Resistance to at Least 1 Drug in Each of the 3 Classes of Licensed Oral Antiretroviral Therapies

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00293254
Enrollment
351
Registered
2006-02-17
Start date
2006-02-28
Completion date
2011-05-31
Last updated
2017-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

Keywords

Treatment Experienced

Brief summary

This study will investigate the safety and efficacy of raltegravir as a therapy for Human Immunodeficiency Virus (HIV)-infected patients failing current therapy with 3-class antiviral resistance.

Detailed description

The primary double-blind study of raltegravir versus placebo was extended to 156 weeks and was followed by an open-label raltegravir phase in which continuing participants from both the raltegravir and placebo groups received open-label raltegravir for an additional 84 weeks for a maximum duration of up to 240 weeks. Participants who had viral failure after Week 16 may have received open-label raltegravir until Week 240.

Interventions

DRUGraltegravir potassium

Raltegravir 400 mg twice daily (b.i.d.) by mouth (p.o.) with optimized background therapy. Treatment period of 48 weeks.

DRUGComparator: placebo

Placebo p.o. b.i.d. with optimized background therapy. Treatment period of 48 weeks.

Sponsors

Merck Sharp & Dohme LLC
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Patient must be HIV positive with HIV RNA values that are within ranges required by the study * Patient must have documented failure of certain antiretroviral therapy * Patient must be on the same antiretroviral therapy for at least the past two months

Exclusion criteria

* Patient less than 16 years old * Additional study criteria will be discussed and identified by the study doctor

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 1616 WeeksPercentage of participants who achieved HIV RNA \<400 copies/mL at Week 16
Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 4848 WeeksPercentage of participants who achieved HIV RNA \<400 copies/mL at Week 48
Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL156 WeeksPercentage of participants who achieved HIV RNA \<400 copies/mL at Week 156
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL240 WeeksPercentage of participants who achieved HIV RNA \<400 Copies/mL at Week 240

Secondary

MeasureTime frameDescription
Double-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response156 WeeksFor participants with confirmed HIV RNA levels \<50 copies/mL on 2 consecutive visits, loss of virologic response is the occurrence of the first value \>50 copies/mL or loss to follow-up; participants who never achieved HIV RNA \<50 copies/mL on 2 consecutive visits are also considered as having loss of virologic response. Events are the numbers of participants with loss of virologic response versus the numbers of participants with no loss of virologic response (event-free).
Change From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16Baseline and Week 16Mean change from baseline at Week 16 in HIV RNA (log 10 copies/mL)
Change From Baseline in HIV RNA (log10 Copies/mL) at Week 48Baseline and Week 48Mean change from baseline at Week 48 in HIV RNA (log10 copies/mL)
Double-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL)Baseline and Week 156Mean change from baseline at Week 156 in HIV RNA (log10 copies/mL)
Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 1616 WeeksPercentage of participants who achieved HIV RNA \<50 copies/mL at Week 16
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 16Baseline and Week 16Mean change from baseline at Week 16 in CD4 cell count (cells/mm\^3)
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 48Baseline and Week 48Mean change from baseline at Week 48 in CD4 cell count (cells/mm\^3)
Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3)Baseline and Week 156Mean change from baseline at Week 156 in CD4 cell count (cells/mm\^3)
Open-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3)Baseline and Week 240Mean change from baseline at Week 240 in CD4 cell count (cells/mm\^3)
Open-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL)Baseline and Week 240Mean change from baseline at Week 240 in HIV RNA (log10 copies/mL)
Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 4848 WeeksPercentage of participants who achieved HIV RNA \<50 copies/mL at Week 48
Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL156 WeeksPercentage of participants who achieved HIV RNA \<50 copies/mL at Week 156
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL240 WeeksPercentage of participants who achieved HIV RNA \<50 copies/mL at Week 240

Participant flow

Recruitment details

Phase 3; First Patient In: 08-Mar-2006; Last Patient Last Visit (LPLV) for Week 48: 31-Jul-2007; Extension Study LPLV Week 240: May 2011 53 sites (US, Brazil, Canada, Colombia, Mexico, and Puerto Rico).

Pre-assignment details

Patients failed prior antiretroviral therapy (HIV RNA \>1000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors). All patients must have met laboratory criteria.

Participants by arm

ArmCount
Raltegravir 400 mg b.i.d. + OBT230
Placebo + OBT119
Total349

Withdrawals & dropouts

PeriodReasonFG000FG001
Extension - Double-Blind Week 49-156Adverse Event41
Extension - Double-Blind Week 49-156Death41
Extension - Double-Blind Week 49-156Entered OLPVF Phase157
Extension - Double-Blind Week 49-156Lack of Efficacy34
Extension - Double-Blind Week 49-156Lost to Follow-up33
Extension - Double-Blind Week 49-156Other Reason102
Extension - Double-Blind Week 49-156Participant Moved/Site Stopped Trial63
Extension - Double-Blind Week 49-156Withdrawal by Subject128
Extension - Open-Label Week 157-240Adverse Event21
Extension - Open-Label Week 157-240Lack of Efficacy10
Extension - Open-Label Week 157-240Lost to Follow-up20
Extension - Open-Label Week 157-240Other Reason40
Extension - Open-Label Week 157-240Withdrawal by Subject10
Open-Label Post Virologic Failure PhaseAdverse Event47
Open-Label Post Virologic Failure PhaseLack of Efficacy1614
Open-Label Post Virologic Failure PhaseLost to Follow-up30
Open-Label Post Virologic Failure PhaseOther Reason12
Open-Label Post Virologic Failure PhaseParticipant Moved/Site Stopped Trial11
Open-Label Post Virologic Failure PhaseWithdrawal by Subject63
Primary Study - Double-Blind Week 0-48Adverse Event21
Primary Study - Double-Blind Week 0-48Death52
Primary Study - Double-Blind Week 0-48Entered OLPVF Phase3557
Primary Study - Double-Blind Week 0-48Lack of Efficacy22
Primary Study - Double-Blind Week 0-48Lost to Follow-up31
Primary Study - Double-Blind Week 0-48Moved or trial terminated at site10
Primary Study - Double-Blind Week 0-48Never Treated20
Primary Study - Double-Blind Week 0-48Withdrawal by Subject51

Baseline characteristics

CharacteristicPlacebo + OBTTotalRaltegravir 400 mg b.i.d. + OBT
Age, Continuous46.5 Years45.7 Years45.3 Years
Cluster of Differentiation 4 (CD4) Cell Count163 cells/mm^3152 cells/mm^3146 cells/mm^3
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)47850 copies/mL48709 copies/mL49159 copies/mL
Race/Ethnicity, Customized
Asian
1 Participants3 Participants2 Participants
Race/Ethnicity, Customized
Black
21 Participants68 Participants47 Participants
Race/Ethnicity, Customized
Hispanic
18 Participants65 Participants47 Participants
Race/Ethnicity, Customized
Native American
0 Participants1 Participants1 Participants
Race/Ethnicity, Customized
Other
2 Participants8 Participants6 Participants
Race/Ethnicity, Customized
White
77 Participants204 Participants127 Participants
Sex: Female, Male
Female
12 Participants32 Participants20 Participants
Sex: Female, Male
Male
107 Participants317 Participants210 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
214 / 230111 / 119
serious
Total, serious adverse events
80 / 23054 / 119

Outcome results

Primary

Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL

Percentage of participants who achieved HIV RNA \<400 copies/mL at Week 156

Time frame: 156 Weeks

Population: The analysis population was based on a non-completer equals failure approach where missing values for participants who discontinued the study for any reason were considered treatment failures.~Participants who experienced virologic failure after Week 16 are counted also as treatment failures for the subsequent virologic efficacy analyses.

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTDouble-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL50.2 Percentage of Participants
Placebo + OBTDouble-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL21.0 Percentage of Participants
Primary

Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL

Percentage of participants who achieved HIV RNA \<400 Copies/mL at Week 240

Time frame: 240 Weeks

Population: The analysis population was based on a non-completer equals failure approach where missing values for participants who discontinued the study for any reason were considered treatment failures.~Participants who experienced virologic failure after Week 16 are counted also as treatment failures for the subsequent virologic efficacy analyses.

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTOpen-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL45.7 Percentage of Participants
Placebo + OBTOpen-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL13.4 Percentage of Participants
Primary

Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 16

Percentage of participants who achieved HIV RNA \<400 copies/mL at Week 16

Time frame: 16 Weeks

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTPercentage of Participants Achieving HIV RNA <400 Copies/mL at Week 1677.3 Percentage of Participants
Placebo + OBTPercentage of Participants Achieving HIV RNA <400 Copies/mL at Week 1642.9 Percentage of Participants
Primary

Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 48

Percentage of participants who achieved HIV RNA \<400 copies/mL at Week 48

Time frame: 48 Weeks

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTPercentage of Participants Achieving HIV RNA <400 Copies/mL at Week 4871.1 Percentage of Participants
Placebo + OBTPercentage of Participants Achieving HIV RNA <400 Copies/mL at Week 4837.8 Percentage of Participants
Secondary

Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 16

Mean change from baseline at Week 16 in CD4 cell count (cells/mm\^3)

Time frame: Baseline and Week 16

Population: Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 cell count (cells/mm\^3) was carried forward for participants who discontinued assigned therapy due to lack of efficacy.

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTChange From Baseline in CD4 Cell Count (Cells/mm^3) at Week 1685.8 CD4 Cell Count (cells/mm^3)
Placebo + OBTChange From Baseline in CD4 Cell Count (Cells/mm^3) at Week 1639.9 CD4 Cell Count (cells/mm^3)
Secondary

Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 48

Mean change from baseline at Week 48 in CD4 cell count (cells/mm\^3)

Time frame: Baseline and Week 48

Population: Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 cell count (cells/mm\^3) was carried forward for participants who discontinued assigned therapy due to lack of efficacy.~Participants with virologic failure after Week 16 are treatment failures for virologic efficacy analyses.

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTChange From Baseline in CD4 Cell Count (Cells/mm^3) at Week 4898.4 CD4 Cell Count (cells/mm^3)
Placebo + OBTChange From Baseline in CD4 Cell Count (Cells/mm^3) at Week 4839.8 CD4 Cell Count (cells/mm^3)
Secondary

Change From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16

Mean change from baseline at Week 16 in HIV RNA (log 10 copies/mL)

Time frame: Baseline and Week 16

Population: Observed mean change from baseline in log10 plasma HIV RNA calculated using conventional imputation (replace \<400 copies by 400 copies if signal detected; 200 copies if not detected); Missing values: Baseline carry-forward for all failures/discontinued due to lack of efficacy

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTChange From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16-1.92 HIV RNA (log10 copies/mL)
Placebo + OBTChange From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16-1.06 HIV RNA (log10 copies/mL)
Secondary

Change From Baseline in HIV RNA (log10 Copies/mL) at Week 48

Mean change from baseline at Week 48 in HIV RNA (log10 copies/mL)

Time frame: Baseline and Week 48

Population: Observed mean change from baseline in log10 plasma HIV RNA calculated using conventional imputation (replace \<400 copies by 400 copies if signal detected; 200 copies if not detected); Missing values: Baseline carry-forward for all failures/discontinued due to lack of efficacy

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTChange From Baseline in HIV RNA (log10 Copies/mL) at Week 48-1.75 HIV RNA (log10 copies/mL)
Placebo + OBTChange From Baseline in HIV RNA (log10 Copies/mL) at Week 48-0.87 HIV RNA (log10 copies/mL)
Secondary

Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3)

Mean change from baseline at Week 156 in CD4 cell count (cells/mm\^3)

Time frame: Baseline and Week 156

Population: Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 cell count (cells/mm\^3) was carried forward for participants who discontinued assigned therapy due to lack of efficacy.~Participants with virologic failure after Week 16 are treatment failures for virologic efficacy analyses.

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTDouble-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3)157.2 CD4 Cell Count (cells/mm^3)
Placebo + OBTDouble-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3)54.2 CD4 Cell Count (cells/mm^3)
Secondary

Double-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL)

Mean change from baseline at Week 156 in HIV RNA (log10 copies/mL)

Time frame: Baseline and Week 156

Population: Observed mean change from baseline in log10 plasma HIV RNA calculated using conventional imputation (replace \<400 copies by 400 copies if signal detected; 200 copies if not detected); Missing values: Baseline carry-forward for all failures/discontinued due to lack of efficacy

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTDouble-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL)-1.37 HIV RNA (log10 copies/mL)
Placebo + OBTDouble-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL)-0.52 HIV RNA (log10 copies/mL)
Secondary

Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL

Percentage of participants who achieved HIV RNA \<50 copies/mL at Week 156

Time frame: 156 Weeks

Population: Participants who experienced virologic failure after Week 16 are also counted as treatment failures for the subsequent virologic efficacy analyses.

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTDouble-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL47.6 Percentage of Participants
Placebo + OBTDouble-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL17.6 Percentage of Participants
Secondary

Double-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response

For participants with confirmed HIV RNA levels \<50 copies/mL on 2 consecutive visits, loss of virologic response is the occurrence of the first value \>50 copies/mL or loss to follow-up; participants who never achieved HIV RNA \<50 copies/mL on 2 consecutive visits are also considered as having loss of virologic response. Events are the numbers of participants with loss of virologic response versus the numbers of participants with no loss of virologic response (event-free).

Time frame: 156 Weeks

Population: Participants who experienced virologic failure after Week 16 are also counted as treatment failures for the subsequent virologic efficacy analyses.

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTDouble-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response44.3 Percentage of Participants
Placebo + OBTDouble-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response17.6 Percentage of Participants
Secondary

Open-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3)

Mean change from baseline at Week 240 in CD4 cell count (cells/mm\^3)

Time frame: Baseline and Week 240

Population: Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 cell count (cells/mm\^3) was carried forward for participants who discontinued assigned therapy due to lack of efficacy.~Participants with virologic failure after Week 16 are treatment failures for virologic efficacy analyses.

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTOpen-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3)172.1 CD4 Cell Count (Cells/mm^3)
Placebo + OBTOpen-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3)54.1 CD4 Cell Count (Cells/mm^3)
Secondary

Open-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL)

Mean change from baseline at Week 240 in HIV RNA (log10 copies/mL)

Time frame: Baseline and Week 240

Population: Observed mean change from baseline in log10 plasma HIV RNA calculated using conventional imputation (replace \<400 copies by 400 copies if signal detected; 200 copies if not detected); Missing values: Baseline carry-forward for all failures/discontinued due to lack of efficacy~Participants with virologic failure after Week 16 = treatment failures

ArmMeasureValue (MEAN)
Raltegravir 400 mg b.i.d. + OBTOpen-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL)-1.31 HIV RNA (log10 copies/mL)
Placebo + OBTOpen-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL)-0.41 HIV RNA (log10 copies/mL)
Secondary

Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL

Percentage of participants who achieved HIV RNA \<50 copies/mL at Week 240

Time frame: 240 Weeks

Population: Participants who experienced virologic failure after Week 16 are also counted as treatment failures for the subsequent virologic efficacy analyses.

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTOpen-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL41.3 Percentage of Participants
Placebo + OBTOpen-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL13.4 Percentage of Participants
Secondary

Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16

Percentage of participants who achieved HIV RNA \<50 copies/mL at Week 16

Time frame: 16 Weeks

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTPercentage of Participants Achieving HIV RNA <50 Copies/mL at Week 1662.0 Percentage of Participants
Placebo + OBTPercentage of Participants Achieving HIV RNA <50 Copies/mL at Week 1636.1 Percentage of Participants
Secondary

Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 48

Percentage of participants who achieved HIV RNA \<50 copies/mL at Week 48

Time frame: 48 Weeks

Population: Participants who experienced virologic failure after Week 16 are also counted as treatment failures for the subsequent virologic efficacy analyses.

ArmMeasureValue (NUMBER)
Raltegravir 400 mg b.i.d. + OBTPercentage of Participants Achieving HIV RNA <50 Copies/mL at Week 4859.6 Percentage of Participants
Placebo + OBTPercentage of Participants Achieving HIV RNA <50 Copies/mL at Week 4834.5 Percentage of Participants

Source: ClinicalTrials.gov · Data processed: Apr 5, 2026