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HIV InfectionPhase 3onceMRKNCT02131233

Evaluation of the Safety and Efficacy of Reformulated Raltegravir (MK-0518) 1200 mg Once Daily in Combination With TRUVADA™ in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-Naive Participants (MK-0518-292)

A Phase 3 study testing Reformulated Raltegravir, Raltegravir and TRUVADA™ in people with HIV Infection, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To evaluate the safety and efficacy of reformulated raltegravir (MK-0518) 1200 mg once daily in combination with TRUVADA™ versus raltegravir 400 mg twice daily in combination with TRUVADA™ in HIV-1 infected, treatment-naive participants. 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?
Reformulated Raltegravir, Raltegravir and TRUVADA™
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
802 participants
Where
No sites listed yet
Study dates
23 May 2014to 19 Dec 2016
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

  • HIV-1 positive
  • Naïve to antiretroviral therapy including investigational antiretroviral agents
  • Not of reproductive potential or, if of reproductive potential agrees to 1) true abstinence, or 2) use of an acceptable method of birth control during the study

Who cannot join

  • Use of recreational or illicit drugs or has recent history of drug or alcohol abuse or dependence
  • Has been treated for a viral infection other than HIV-1 (such as hepatitis B) with an agent that is active against HIV-1 including but not limited to adefovir, tenofovir, entecavir, emtricitabine, or lamivudine
  • Has documented or known resistance to raltegravir, emtricitabine, and/or tenofovir before the first dose of study drug
  • Has participated in a study with an investigational compound or device within 30 days or anticipates participating in such a study during this study
  • Has used systemic immunosuppressive therapy or immune modulators within 30 days or is anticipated to need them during the study (short courses of corticosteroids are allowed)
  • Requires or is anticipated to require any of the following prohibited medications while in the study: phenobarbital, phenytoin, rifampin, rifabutin, or calcium, magnesium and aluminum containing antacids, such as TUMS™, Maalox™ and Milk of Magnesia™
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  • Has significant hypersensitivity or other contraindication to any of the components of the study drugs
  • Has current, active diagnosis of acute hepatitis due to any cause
  • Is pregnant, breastfeeding, or expecting to conceive during the study
  • Female participant expecting to donate eggs or male participant expecting to donate sperm during the study
  • Is or has a family member (spouse or children) who is investigational staff or sponsor staff directly involved in this trial

About this study

Official title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Reformulated Raltegravir 1200 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Each in Combination With TRUVADA™, in Treatment-Naïve HIV-1 Infected Subjects

To evaluate the safety and efficacy of reformulated raltegravir (MK-0518) 1200 mg once daily in combination with TRUVADA™ versus raltegravir 400 mg twice daily in combination with TRUVADA™ in HIV-1 infected, treatment-naive participants. The primary hypothesis being tested is that reformulated raltegravir 1200 mg once-daily is non-inferior to raltegravir 400 mg twice-daily, each in combination therapy with TRUVADA™, as assessed by the proportion of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL at Week 48.

Conditions
HIV Infection
Being tested
Reformulated Raltegravir, Raltegravir, TRUVADA™, Placebo to Reformulated Raltegravir, Placebo to Raltegravir
Medical subject headings
HIV Infections

What participants receive

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

  • Reformulated RaltegravirDrug

    Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily

  • RaltegravirDrug

    Raltegravir 400 mg tablet orally twice daily

  • TRUVADA™Drug

    Emtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label)

  • Placebo to Reformulated RaltegravirDrug

    Placebo to reformulated raltegravir 2 tablets orally once daily

  • Placebo to RaltegravirDrug

    Placebo to raltegravir 1 tablet orally twice daily

Study groups in NCT02131233
Study groupRoleWhat they receive
Reformulated RaltegravirExperimentalReformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks
Receives: Drug: Reformulated Raltegravir; Drug: TRUVADA™; Drug: Placebo to Raltegravir
RaltegravirActive comparatorRaltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks
Receives: Drug: Raltegravir; Drug: TRUVADA™; Drug: Placebo to Reformulated Raltegravir

What is being measured

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

  1. Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48

    From blood samples collected at week 48, HIV-1 RNA levels were determined by the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification (LoQ) of 40 copies/mL. The NC=F approach as defined by FDA "snapshot" approach was used as the primary approach to analysis where all missing data were treated as failures regardless of the reason.

    Measured: Week 48

Secondary outcomes (13)
  1. Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 96

    From blood samples collected at week 96, HIV-1 RNA levels were determined by the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification (LoQ) of 40 copies/mL. The NC=F approach as defined by FDA "snapshot" approach was used as the primary approach to analysis where all missing data were treated as failures regardless of the reason.

    Measured: Week 96

  2. Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48

    CD4 cells were counted from blood collected at baseline and week 48, and the change from baseline determined from week 48 minus baseline values.

    Measured: Baseline and Week 48

  3. Change From Baseline in CD4 Cell Count at Week 96

    CD4 cells were counted from blood collected at baseline and week 96, and the change from baseline determined from week 96 minus baseline values.

    Measured: Baseline and Week 96

  4. Percentage of Participants With an Adverse Event (AE) at Week 48

    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

    Measured: Up to Week 48

  5. Percentage of Participants With an AE After 96 Weeks of Treatment

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

    Measured: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)

  6. Percentage of Participants With a Drug-Related AE at Week 48

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician evaluated whether or not an AE was drug-related.

    Measured: Up to Week 48

  7. Percentage of Participants With a Drug-Related AE After 96 Weeks of Treatment

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. An investigator who is a qualified physician evaluated whether or not an AE was drug-related.

    Measured: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)

  8. Percentage of Participants With a Serious Adverse Event (SAE) at Week 48

    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.

    Measured: Up to Week 48

  9. Percentage of Participants With a SAE After 96 Weeks of Treatment

    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event.

    Measured: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)

  10. Percentage of Participants With a Serious and Drug-Related AE at Week 48

    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. An investigator who is a qualified physician evaluated whether or not a SAE is drug-related.

    Measured: Up to Week 48

  11. Percentage of Participants With a Serious and Drug-Related AE After 96 Weeks of Treatment

    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. An investigator who is a qualified physician evaluated whether or not a SAE is drug-related.

    Measured: Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)

  12. Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE

    Measured: Up to Week 48

  13. Percentage of Participants Who Discontinued From Drug Therapy Due to an AE up to Week 96

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE

    Measured: Up to Week 96

Timeline

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

  1. First posted6 May 2014 (estimated)
  2. Study start23 May 2014
  3. Primary completion21 Dec 2015
  4. Study completion19 Dec 2016

Resources

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
802 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02131233
Sponsor's protocol ID
0518-292
Other IDs
2013-001939-47
Acronym
onceMRK
Status last verified
Jan 2019
First submitted
2 May 2014
Last updated
30 Jan 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Cahn P, Kaplan R, Sax PE, Squires K, Molina JM, Avihingsanon A, Ratanasuwan W, Rojas E, Rassool M, Bloch M, Vandekerckhove L, Ruane P, Yazdanpanah Y, Katlama C, Xu X, Rodgers A, East L, Wenning L, Rawlins S, Homony B, Sklar P, Nguyen BY, Leavitt R, Teppler H; ONCEMRK Study Group. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV. 2017 Nov;4(11):e486-e494. doi: 10.1016/S2352-3018(17)30128-5. Epub 2017 Sep 11.

    PubMed 28918877
  • Cahn P, Sax PE, Squires K, Molina JM, Ratanasuwan W, Rassool M, Bloch M, Xu X, Zhou Y, Homony B, Hepler D, Teppler H, Hanna GJ, Nguyen BY, Greaves W; ONCEMRK Study Group. Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial. J Acquir Immune Defic Syndr. 2018 Aug 15;78(5):589-598. doi: 10.1097/QAI.0000000000001723.

    PubMed 29771789

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Reformulated Raltegravir, Raltegravir and TRUVADA™ 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 3 inclusion and 11 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: finished, as of the sponsor's last update on 30 Jan 2019. 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 31 Oct 2016). 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?

Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48 (time frame: Week 48). 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 NCT02131233, which also lists 2 linked publications.

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 30 Jan 2019.

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