HIV
Conditions
Keywords
HIV Infections, Treatment Naïve
Brief summary
A study to evaluate the safety, tolerability and efficacy of once daily Raltegravir compared to twice daily raltegravir when each is given in combination with TRUVADA™ in treatment-naïve human immunodeficiency virus (HIV)-infected patients.
Detailed description
Following the 96-week double-blind study period (MK0518-071)(NCT00745823), subjects may enroll in an extension study (MK0518-071-10)(NCT00745823). From weeks 96 to 120, subjects' treatment assignments will remain as in the base study. From week 120 to 240, all subjects will receive open-label raltegravir (800 mg, once daily) in combination with TRUVADA™.
Interventions
DRUGComparator: Raltegravir 400 mg b.i.d.
Raltegravir 400 mg tablet by mouth (PO) twice daily (b.i.d.) + two raltegravir placebo tablets + one tablet of TRUVADA™ once daily (q.d.)
DRUGExperimental: Raltegravir 800 mg q.d.
Raltegravir 800 mg tablet PO q.d. + two raltegravir placebo tablets + one tablet TRUVADA™ q.d.
DRUGTRUVADA™
One tablet TRUVADA™ q.d. (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is male or female 18 years of age or older * Patient is HIV positive * Patient is naïve to antiretroviral therapy (ART) or has received less than 7 days total of any ART Extension Study: * The planned extension study did not take place as the study was terminated after the Week 48 analysis.
Exclusion criteria
* Patient is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence * Patient has documented resistance to tenofovir or emtricitabine * Patient is currently participating or has participated in a study with an investigational compound or device within 45 days of signing informed consent * Patient is pregnant or breastfeeding, or expecting to conceive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks | Week 48 |
| Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks | Week 48 |
| Number of Participants With One or More Adverse Events at 48 Weeks | Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks | Week 96 | As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed. |
| Mean Change From Baseline to Week 96 in CD4 Cell Count | Baseline and Week 96 | As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed. |
| Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks | 48 weeks | — |
| Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks | Week 96 | As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed. |
| Number of Participants With One or More Adverse Events at 96 Weeks | Week 96 | As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed. |
| Mean Change From Baseline to Week 48 in CD4 Cell Count | Baseline and Week 48 | — |
| Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks | Week 96 | As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir 800 mg q.d. Raltegravir 800 mg by mouth (PO) once daily (q.d.) plus placebo to raltegravir PO twice daily (b.i.d.) plus one tablet of TRUVADA™ for 96 weeks | 386 |
| Raltegravir 400 mg b.i.d. Raltegravir 400 mg PO b.i.d. plus placebo to raltegravir PO q.d. plus one tablet of TRUVADA™ for 96 weeks | 389 |
| Total | 775 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Lack of Efficacy | 20 | 6 |
| Overall Study | Lost to Follow-up | 10 | 11 |
| Overall Study | Physician Decision | 10 | 5 |
| Overall Study | Pregnancy | 0 | 4 |
| Overall Study | Study Terminated by Sponsor | 326 | 349 |
| Overall Study | Withdrawal by Subject | 14 | 8 |
Baseline characteristics
| Characteristic | Raltegravir 800 mg q.d. | Raltegravir 400 mg b.i.d. | Total |
|---|---|---|---|
| Age, Customized >=64 years | 4 participants | 7 participants | 11 participants |
| Age, Customized Between 18 and 64 years | 382 participants | 382 participants | 764 participants |
| Sex: Female, Male Female | 68 Participants | 90 Participants | 158 Participants |
| Sex: Female, Male Male | 318 Participants | 299 Participants | 617 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 287 / 382 | 282 / 388 |
| serious Total, serious adverse events | 29 / 382 | 46 / 388 |
Outcome results
Primary
Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks
Time frame: Week 48
Population: Data were analyzed for all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir 800 mg q.d. | Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks | 4 Participants |
| Raltegravir 400 mg b.i.d. | Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks | 3 Participants |
95% CI: [-1.3, 2]
Primary
Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks
Time frame: Week 48
Population: Data were analyzed for all participants treated with study drug. Participants who did not complete the study were treated as treatment failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir 800 mg q.d. | Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks | 318 Participants |
| Raltegravir 400 mg b.i.d. | Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks | 343 Participants |
p-value: 0.04495% CI: [-10.7, -0.83]Miettinen and Nurminen
Primary
Number of Participants With One or More Adverse Events at 48 Weeks
Time frame: Week 48
Population: Data were analyzed for all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir 800 mg q.d. | Number of Participants With One or More Adverse Events at 48 Weeks | 331 Participants |
| Raltegravir 400 mg b.i.d. | Number of Participants With One or More Adverse Events at 48 Weeks | 337 Participants |
95% CI: [-5, 4.6]Miettinen and Nurminen
Secondary
Mean Change From Baseline to Week 48 in CD4 Cell Count
Time frame: Baseline and Week 48
Population: Data were analyzed for all participants treated with study drug. Baseline values were carried forward for participants who discontinued treatment due to lack of efficacy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Raltegravir 800 mg q.d. | Mean Change From Baseline to Week 48 in CD4 Cell Count | 209.76 cells/mm^3 |
| Raltegravir 400 mg b.i.d. | Mean Change From Baseline to Week 48 in CD4 Cell Count | 196.20 cells/mm^3 |
95% CI: [-7.29, 34.4]t-test, 2 sided
Secondary
Mean Change From Baseline to Week 96 in CD4 Cell Count
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time frame: Baseline and Week 96
Population: The Week 96 data analysis was not performed.
Secondary
Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time frame: Week 96
Secondary
Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks
Time frame: 48 weeks
Population: Data were analyzed for all participants treated with study drug. Participants who did not complete the study were treated as treatment failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir 800 mg q.d. | Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks | 338 Participants |
| Raltegravir 400 mg b.i.d. | Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks | 361 Participants |
p-value: 0.01195% CI: [-9.29, -1.06]Miettinen and Nurminen
Secondary
Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time frame: Week 96
Population: The Week 96 data analysis was not performed.
Secondary
Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time frame: Week 96
Population: The Week 96 data analysis was not performed.
Secondary
Number of Participants With One or More Adverse Events at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Time frame: Week 96