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) (onceMRK)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme Corp.

ClinicalTrials.gov Identifier:

NCT02131233

First received: May 2, 2014

Last updated: May 17, 2017

Last verified: May 2017

History of Changes

Results First Received: September 7, 2016

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Participant, Investigator, Outcomes Assessor; Primary Purpose: Treatment
Condition:	HIV Infection
Interventions:	Drug: Reformulated Raltegravir Drug: Raltegravir Drug: TRUVADA™ Drug: Placebo to Reformulated Raltegravir Drug: Placebo to Raltegravir

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
These results stop at the primary data cutoff at Week 48

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Participant Flow: Overall Study

	Reformulated Raltegravir	Raltegravir
STARTED	533 ^[1]	269 ^[1]
Treated	531	266
COMPLETED	490 ^[2]	242 ^[2]
NOT COMPLETED	43	27
Not Treated	2	3
Adverse Event	6	6
Death	0	1
Lack of Efficacy	4	1
Lost to Follow-up	8	4
Non-Compliance With Study Drug	5	4
Physician Decision	4	0
Pregnancy	2	0
Withdrawal by Subject	12	8

^[1]	Enrolled participants
^[2]	Completed to Week 48

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Participants

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks
Total	Total of all reporting groups

Baseline Measures

	Reformulated Raltegravir	Raltegravir	Total
Overall Participants Analyzed [Units: Participants]	531	266	797

Age [Units: Years] Mean (Standard Deviation)	35.4 (10.3)	36.9 (11.0)	35.9 (10.5)

Sex: Female, Male [Units: Participants] Count of Participants
Female	91 17.1%	32 12.0%	123 15.4%
Male	440 82.9%	234 88.0%	674 84.6%

Outcome Measures

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1. Primary:

Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48 [ Time Frame: Week 48 ]

Measure Type	Primary
Measure Title	Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48
Measure Description	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.
Time Frame	Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	531	266
Percentage of Participants Achieving <40 Copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48 [Units: Percentage of participants] Number (95% Confidence Interval)	88.9 (85.9 to 91.4)	88.3 (83.9 to 91.9)

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

Groups ^[1]	All groups
Statistical Test Type ^[2]	Non-Inferiority or Equivalence
Estimated Difference ^[3]	0.510
95% Confidence Interval	-4.204 to 5.223

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The 95% Confidence Interval (CI) for the treatment differences in percent response were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA <=100,000 copies/mL or HIV-1 RNA >100,000 copies/mL)
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Reformulated Raltegravir is concluded non-inferior to Raltegravir if the lower bound of the 95% CI for the difference in percent response is above -10 percentage points.
[3]	Other relevant estimation information:
	Reformulated Raltegravir minus Raltegravir

2. Secondary:

Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48 [ Time Frame: Baseline and Week 48 ]

Measure Type	Secondary
Measure Title	Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48
Measure Description	CD4 cells were counted from blood collected at baseline and week 48, and the change from baseline determined from week 48 minus baseline values.
Time Frame	Baseline and Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment and have baseline data. The Observed Failure (OF) approach to handling missing values assumed baseline-carry-forward for all failures, and excluded other missing values.

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	499	251
Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48 [Units: Cells/mm^3] Mean (95% Confidence Interval)	232.0 (214.6 to 249.4)	234.1 (212.8 to 255.3)

Statistical Analysis 1 for Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Mean Difference (Final Values) ^[3]	-2.1
95% Confidence Interval	-30.9 to 26.7

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The 95% CI for mean difference in CD4 change was based on t-distribution.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant estimation information:
	Reformulated Raltegravir minus Raltegravir

3. Secondary:

Percentage of Participants With an Adverse Event (AE) at Week 48 [ Time Frame: Up to Week 48 ]

Measure Type	Secondary
Measure Title	Percentage of Participants With an Adverse Event (AE) at Week 48
Measure Description	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.
Time Frame	Up to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	531	266
Percentage of Participants With an Adverse Event (AE) at Week 48 [Units: Percentage of participants]	83.2	88.0

No statistical analysis provided for Percentage of Participants With an Adverse Event (AE) at Week 48

4. Secondary:

Percentage of Participants With a Drug-Related AE at Week 48 [ Time Frame: Up to Week 48 ]

Measure Type	Secondary
Measure Title	Percentage of Participants With a Drug-Related AE at Week 48
Measure Description	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.
Time Frame	Up to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	531	266
Percentage of Participants With a Drug-Related AE at Week 48 [Units: Percentage of participants]	25.0	27.1

No statistical analysis provided for Percentage of Participants With a Drug-Related AE at Week 48

5. Secondary:

Percentage of Participants With a Serious Adverse Event (SAE) at Week 48 [ Time Frame: Up to Week 48 ]

Measure Type	Secondary
Measure Title	Percentage of Participants With a Serious Adverse Event (SAE) at Week 48
Measure Description	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.
Time Frame	Up to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	531	266
Percentage of Participants With a Serious Adverse Event (SAE) at Week 48 [Units: Percentage of participants]	6.2	9.4

No statistical analysis provided for Percentage of Participants With a Serious Adverse Event (SAE) at Week 48

6. Secondary:

Percentage of Participants With a Serious and Drug-Related AE at Week 48 [ Time Frame: Up to Week 48 ]

Measure Type	Secondary
Measure Title	Percentage of Participants With a Serious and Drug-Related AE at Week 48
Measure Description	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.
Time Frame	Up to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	531	266
Percentage of Participants With a Serious and Drug-Related AE at Week 48 [Units: Percentage of participants]	0.2	0.8

No statistical analysis provided for Percentage of Participants With a Serious and Drug-Related AE at Week 48

7. Secondary:

Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48 [ Time Frame: Up to Week 48 ]

Measure Type	Secondary
Measure Title	Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48
Measure Description	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
Time Frame	Up to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups

	Description
Reformulated Raltegravir	Reformulated 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
Raltegravir	Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

Measured Values

	Reformulated Raltegravir	Raltegravir
Participants Analyzed [Units: Participants]	531	266
Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48 [Units: Percentage of participants]	1.1	2.3

No statistical analysis provided for Percentage of Participants Who Discontinued From Drug Therapy Due to an AE at Week 48

8. Secondary:

Percentage of Participants Achieving <40 Copies/mL HIV-1 RNA at Week 96 [ Time Frame: Week 96 ]