HIV InfectionPhase 3NCT00443703

MK0518 in the Treatment of HIV-Infected Patients Switched From a Protease Inhibitor Regimen (0518-032)(TERMINATED)

A Phase 3 study testing MK0518 (raltegravir) and Comparator: KALETRA™ (lopinavir (+) ritonavir ) in people with HIV Infection, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to investigate the efficacy, safety, and tolerability of an investigational treatment for patients with HIV. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV Infection
What is being tested?: MK0518 (raltegravir) and Comparator: KALETRA™ (lopinavir (+) ritonavir )
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 352 participants
Where: No sites listed yet
Study dates: May 2007to Apr 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient is at least 18 years of age
Patient is Human Immunodeficiency Virus (HIV) positive
Patient has documented Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 copies/milliliter (mL) for at least 3 months while on a KALETRA based regimen
Patient has been on a KALETRA based regimen for at least 3 months without a change in background antiretroviral therapy
Patient has no documentation of HIV RNA >50 copies/mL for at least 3 months while on the KALETRA based regimen

Who cannot join

Patient is or plans to become pregnant, or nursing a child
Patient plans to donate eggs or impregnate/donate sperm
Patient is receiving Stavudine (d4T) as a component of the background antiretroviral therapy
Patient is currently receiving a second protease inhibitor in addition to KALETRA
Patient is currently receiving, or has received in the past twelve weeks, treatment for the management of elevated lipids
Patient has used another experimental HIV-integrase inhibitor
Patient has a current (active) diagnosis of acute hepatitis due to any cause
Patient has used systemic immunosuppressive therapy within one month prior to treatment in this study

About this study

Official title: A Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK0518 Versus KALETRA in HIV-Infected Patients Switched From a Stable KALETRA-Based Regimen - Study A

The purpose of this study is to investigate the efficacy, safety, and tolerability of an investigational treatment for patients with HIV.

Conditions: HIV Infection
Being tested: MK0518 (raltegravir), Comparator: KALETRA™ (lopinavir (+) ritonavir ), Comparator: placebo
Keywords: treatment experienced
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK0518 (raltegravir)Drug
Also called MK0518, raltegravir
MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d) for up to 48 weeks of treatment
Comparator: KALETRA™ (lopinavir (+) ritonavir )Drug
Also called KALETRA
KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) for up to 48 weeks of treatment.
Comparator: placeboDrug
MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment
Comparator: placeboDrug
KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment.

Study groups in NCT00443703
Study group	Role	What they receive
1	Experimental	Arm 1: MK0518 (raltegravir) + placebo to KALETRA™ (lopinavir (+) ritonavir ) Receives: Drug: MK0518 (raltegravir); Drug: Comparator: placebo
2	Active comparator	Arm 2: KALETRA™ (lopinavir (+) ritonavir) + placebo to MK0518 (raltegravir) Receives: Drug: Comparator: KALETRA™ (lopinavir (+) ritonavir ); Drug: Comparator: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients With Plasma Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 Copies/mL at Week 24
Measured: Week 24
Number of Patients With Clinical Adverse Experiences (CAEs) Through 24 Weeks
An adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S (Merck \& Co., Inc.) product, whether or not considered related to the use of the product
Measured: 24 Week last patient last visit
Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 12
Measured: Baseline and Week 12
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Measured: Baseline and Week 12
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Measured: Baseline and Week 12
Mean Percent Change From Baseline in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Measured: Baseline and Week 12
Median Percent Change From Baseline in Serum Triglyceride at Week 12
Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.
Measured: Baseline and Week 12

Secondary outcomes (5)

Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 24
Measured: Baseline and Week 24
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24
Measured: Baseline and Week 24
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24
Measured: Baseline and Week 24
Mean Percent Change From Baseline in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C) at Week 24
Measured: Baseline and Week 24
Median Percent Change From Baseline in Serum Triglyceride at Week 24
Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.
Measured: Baseline and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Apr 2009

First posted6 Mar 2007 (estimated)
Study startMay 2007
Primary completionApr 2009
Study completionApr 2009

Why it stopped: primary efficacy analysis at Week 24 did not demonstrate non-inferiority of raltegravir versus lopinavir (+) ritonavir

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 352 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00443703
Sponsor's protocol ID: 0518-032
Other IDs: 2007_507
Status last verified: Feb 2017
First submitted: 2 Mar 2007
Last updated: 21 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fatkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Xu X, Sklar P; SWITCHMRK 1 and 2 investigators. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010 Jan 30;375(9712):396-407. doi: 10.1016/S0140-6736(09)62041-9. Epub 2010 Jan 12.
PubMed 20074791

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK0518 Versus KALETRA in HIV-Infected Patients Switched From a Stable KALETRA-Based Regimen - Study A
ClinicalTrials.gov ID: NCT00443703
Acronym / sponsor ID: 0518-032
Conditions: HIV Infection
Keywords: treatment experienced
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: primary efficacy analysis at Week 24 did not demonstrate non-inferiority of raltegravir versus lopinavir (+) ritonavir
Enrolment: 352 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: May 2007
Primary completion: Apr 2009 (actual)
Study completion: Apr 2009 (actual)
First posted: 6 Mar 2007 (estimated)
Results: Posted 1 Dec 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to investigate the efficacy, safety, and tolerability of an investigational treatment for patients with HIV.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: MK0518 (raltegravir), Drug: Comparator: placeboArm 1: MK0518 (raltegravir) + placebo to KALETRA™ (lopinavir (+) ritonavir )
2	Active comparator	Drug: Comparator: KALETRA™ (lopinavir (+) ritonavir ), Drug: Comparator: placeboArm 2: KALETRA™ (lopinavir (+) ritonavir) + placebo to MK0518 (raltegravir)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patient is at least 18 years of age
Patient is Human Immunodeficiency Virus (HIV) positive
Patient has documented Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 copies/milliliter (mL) for at least 3 months while on a KALETRA based regimen
Patient has been on a KALETRA based regimen for at least 3 months without a change in background antiretroviral therapy
Patient has no documentation of HIV RNA >50 copies/mL for at least 3 months while on the KALETRA based regimen

Key exclusion criteria (8 listed)

Patient is or plans to become pregnant, or nursing a child
Patient plans to donate eggs or impregnate/donate sperm
Patient is receiving Stavudine (d4T) as a component of the background antiretroviral therapy
Patient is currently receiving a second protease inhibitor in addition to KALETRA
Patient is currently receiving, or has received in the past twelve weeks, treatment for the management of elevated lipids

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK0518 (raltegravir)Also: MK0518, raltegravirMK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d) for up to 48 weeks of treatment	Drug	1
Comparator: KALETRA™ (lopinavir (+) ritonavir )Also: KALETRAKALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) for up to 48 weeks of treatment.	Drug	2
Comparator: placeboMK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment	Drug	2
Comparator: placeboKALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment.	Drug	1

Primary outcome

Number of Patients With Plasma Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 Copies/mL at Week 24
Time frame: Week 24
Number of Patients With Clinical Adverse Experiences (CAEs) Through 24 Weeks
Time frame: 24 Week last patient last visit
An adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S (Merck \& Co., Inc.) product, whether or not considered related to the use of the product
Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 12
Time frame: Baseline and Week 12
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Time frame: Baseline and Week 12
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
Mean Percent Change From Baseline in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline and Week 12
Median Percent Change From Baseline in Serum Triglyceride at Week 12
Time frame: Baseline and Week 12
Standard Deviation (Robust): calculated as interquartile range (IQR)/1.075, where IQR=3rd quartile-1st quartile.

5 secondary outcomes

Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 24
Time frame: Baseline and Week 24
Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24
Time frame: Baseline and Week 24
Mean Percent Change From Baseline in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24
Time frame: Baseline and Week 24
Mean Percent Change From Baseline in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C) at Week 24
Time frame: Baseline and Week 24
Median Percent Change From Baseline in Serum Triglyceride at Week 24
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 1 Dec 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK0518 400 mg b.i.d.	177	149
KALETRA™ 400/100 mg b.i.d.	175	157

Primary outcome: Number of Patients With Plasma Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 Copies/mL at Week 24

Time frame: Week 24. Number. Unit: Participants

Measure	MK0518 400 mg b.i.d. n = 172	KALETRA™ 400/100 mg b.i.d. n = 174
Value	139	152

Population analysed: Full analysis set; two patients were excluded from the analysis because they did not have an HIV RNA test performed at Week 24 but had a test result of HIV RNA \<50 copies/mL at Week 12 and Week 36.

Primary outcome: Number of Patients With Clinical Adverse Experiences (CAEs) Through 24 Weeks

Time frame: 24 Week last patient last visit. Number. Unit: Participants

Measure	MK0518 400 mg b.i.d. n = 174	KALETRA™ 400/100 mg b.i.d. n = 174
With CAEs	109	106
Without CAEs	65	68

Population analysed: All patients who took study medication were included in the analysis

Primary outcome: Mean Percent Change From Baseline in Fasting Serum Cholesterol at Week 12

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: Percent Change

Measure	MK0518 400 mg b.i.d. n = 142	KALETRA™ 400/100 mg b.i.d. n = 146
Value	-12.83 (12.19)	0.70 (14.69)

Population analysed: Patients who had both baseline and at least one post-baseline measurement were included in the analysis

Primary outcome: Mean Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: Percent Change

Measure	MK0518 400 mg b.i.d. n = 140	KALETRA™ 400/100 mg b.i.d. n = 145
Value	-15.17 (15.80)	2.31 (19.37)

Population analysed: Patients who had both baseline and at least one post-baseline measurement were included in the analysis

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse experiences that occurred after randomization and through Week 24 last patient last visit (31-Oct-2008) were collected.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK0518 400 mg b.i.d.	15 of 174 (8.6%)	76 of 174 (43.7%)	Not reported
KALETRA™ 400/100 mg b.i.d.	10 of 174 (5.7%)	77 of 174 (44.3%)	Not reported

Limitations and caveats (from the sponsor): The reason for early termination: Study was terminated after the primary efficacy analysis at Week 24 did not demonstrate non-inferiority of MK0518 versus KALETRA™.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 20074791Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fatkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Xu X, Sklar P; SWITCHMRK 1 and 2 investigators. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010 Jan 30;375(9712):396-407. doi: 10.1016/S0140-6736(09)62041-9. Epub 2010 Jan 12.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MK0518 (raltegravir) and Comparator: KALETRA™ (lopinavir (+) ritonavir ) in people with HIV Infection, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Plasma Human Immunodeficiency Virus (HIV) RiboNucleic Acid (RNA) <50 Copies/mL at Week 24 (time frame: Week 24). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00443703, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2017.