Human Immunodeficiency Virus
Conditions
Brief summary
A study to test the safety and effect of twice daily raltegravir in a diverse cohort of patients currently infected with human immunodeficiency virus (HIV), where at least 50% are African American and at least 25% are female, either having received antiretroviral drugs before or not.
Interventions
400 mg tablets taken twice daily. Total treatment period is 48 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is HIV positive * Patient agrees to use (or have their partner use) birth control as defined by the study doctor
Exclusion criteria
* If female, pregnant or breastfeeding * Patient has used an investigational agent in the last 30 days * Patient has acute hepatitis * Patient has received MK0518 (raltegravir) before * Patient has used another experimental HIV-integrase inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Week 48 | Numbers of participants with HIV RNA copies \<50 copies/mL were summarized by race for each time point. |
| Number of Participants With One or More Adverse Events | Week 48 | Numbers of participants with one or more adverse events were summarized by race. |
| Number of Participants Who Discontinued Due to an Adverse Event | Week 48 | Numbers of participants who discontinued due to an adverse event were summarized by race. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Week 48 | Numbers of participants with HIV RNA copies \<400 copies/mL were summarized by race for each time point. |
| Number of Participants Without Loss of Virologic Response | Week 48 | 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). |
| Mean Change From Baseline to Week 48 in HIV RNA | Baseline and Week 48 | Mean changes from baseline in plasma HIV RNA were summarized by race at each time point. |
| Mean Change From Baseline to Week 48 in CD4 Cell Count | Baseline and Week 48 | Mean changes from baseline in CD4 cell counts were summarized by race at each time point. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Failing Current Therapy Participants with previous HIV treatment experience who did not respond to their current HIV therapy were treated with open-label raltegravir 400 mg b.i.d. plus other antiretroviral agents at the discretion of the investigator. | 97 |
| Participants Intolerant to Current Therapy Participants with previous HIV treatment experience who could not tolerate the treatment were treated with open-label raltegravir 400 mg b.i.d. plus other antiretroviral agents at the discretion of the investigator. | 88 |
| Participants Treatment Naive Participants with no previous HIV treatment were treated with open-label raltegravir 400 mg b.i.d. plus other antiretroviral agents at the discretion of the investigator. | 21 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 4 | 0 |
| Overall Study | Never Treated | 1 | 1 | 1 |
| Overall Study | Physician Decision | 2 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 6 | 2 |
Baseline characteristics
| Characteristic | Participants Failing Current Therapy | Participants Intolerant to Current Therapy | Participants Treatment Naive | Total |
|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 9.2 | 46.9 years STANDARD_DEVIATION 9 | 38.5 years STANDARD_DEVIATION 10.1 | 44.7 years STANDARD_DEVIATION 9.5 |
| Race Black | 70 Participants | 69 Participants | 14 Participants | 153 Participants |
| Race Non-Black | 27 Participants | 19 Participants | 7 Participants | 53 Participants |
| Sex: Female, Male Female | 46 Participants | 44 Participants | 7 Participants | 97 Participants |
| Sex: Female, Male Male | 51 Participants | 44 Participants | 14 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 49 / 97 | 26 / 88 | 10 / 21 |
| serious Total, serious adverse events | 15 / 97 | 5 / 88 | 2 / 21 |
Outcome results
Primary
Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
Numbers of participants with HIV RNA copies \<50 copies/mL were summarized by race for each time point.
Time frame: Week 48
Population: Efficacy analyses were based on the Full Analysis Set population that included all participants who took at least one dose of study medication and had at least one postbaseline evaluation.~The Treatment-Related Discontinuation = Failure approach was used as the primary method for handling missing HIV RNA values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Black (n = 69, 62, 14) | 44 Participants |
| Treatment Experienced - Failing Current Therapy | Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Non-Black (n = 25, 18, 7) | 16 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Black (n = 69, 62, 14) | 43 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Non-Black (n = 25, 18, 7) | 18 Participants |
| Treatment Naive | Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Black (n = 69, 62, 14) | 11 Participants |
| Treatment Naive | Number of Participants Who Achieved HIV Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Non-Black (n = 25, 18, 7) | 5 Participants |
Primary
Number of Participants Who Discontinued Due to an Adverse Event
Numbers of participants who discontinued due to an adverse event were summarized by race.
Time frame: Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Number of Participants Who Discontinued Due to an Adverse Event | Black (n = 70, 69, 14) | 1 Participants |
| Treatment Experienced - Failing Current Therapy | Number of Participants Who Discontinued Due to an Adverse Event | Non-black (n = 27, 19, 7) | 0 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Who Discontinued Due to an Adverse Event | Black (n = 70, 69, 14) | 2 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Who Discontinued Due to an Adverse Event | Non-black (n = 27, 19, 7) | 0 Participants |
| Treatment Naive | Number of Participants Who Discontinued Due to an Adverse Event | Black (n = 70, 69, 14) | 1 Participants |
| Treatment Naive | Number of Participants Who Discontinued Due to an Adverse Event | Non-black (n = 27, 19, 7) | 0 Participants |
Primary
Number of Participants With One or More Adverse Events
Numbers of participants with one or more adverse events were summarized by race.
Time frame: Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Number of Participants With One or More Adverse Events | Non-Black (n = 27, 19, 7) | 23 Participants |
| Treatment Experienced - Failing Current Therapy | Number of Participants With One or More Adverse Events | Black (n = 70, 69, 14) | 55 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants With One or More Adverse Events | Black (n = 70, 69, 14) | 40 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants With One or More Adverse Events | Non-Black (n = 27, 19, 7) | 13 Participants |
| Treatment Naive | Number of Participants With One or More Adverse Events | Black (n = 70, 69, 14) | 12 Participants |
| Treatment Naive | Number of Participants With One or More Adverse Events | Non-Black (n = 27, 19, 7) | 6 Participants |
Secondary
Mean Change From Baseline to Week 48 in CD4 Cell Count
Mean changes from baseline in CD4 cell counts were summarized by race at each time point.
Time frame: Baseline and Week 48
Population: Efficacy analyses were based on the Full Analysis Set population that included all participants who took at least one dose of study medication and had baseline and at least one postbaseline evaluation.~Baseline values were carried forward for participants who discontinued before Week 48 due to lack of efficacy.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Mean Change From Baseline to Week 48 in CD4 Cell Count | Black (n = 66, 61, 12) | 141.0 cells/mm^3 |
| Treatment Experienced - Failing Current Therapy | Mean Change From Baseline to Week 48 in CD4 Cell Count | Non-Black (n = 23, 15, 7) | 113.1 cells/mm^3 |
| Treatment Experienced - Treatment Intolerant | Mean Change From Baseline to Week 48 in CD4 Cell Count | Black (n = 66, 61, 12) | 62.3 cells/mm^3 |
| Treatment Experienced - Treatment Intolerant | Mean Change From Baseline to Week 48 in CD4 Cell Count | Non-Black (n = 23, 15, 7) | 69.2 cells/mm^3 |
| Treatment Naive | Mean Change From Baseline to Week 48 in CD4 Cell Count | Black (n = 66, 61, 12) | 208.8 cells/mm^3 |
| Treatment Naive | Mean Change From Baseline to Week 48 in CD4 Cell Count | Non-Black (n = 23, 15, 7) | 164.4 cells/mm^3 |
Secondary
Mean Change From Baseline to Week 48 in HIV RNA
Mean changes from baseline in plasma HIV RNA were summarized by race at each time point.
Time frame: Baseline and Week 48
Population: Efficacy analyses were based on the Full Analysis Set population that included all participants who took at least one dose of study medication and had baseline and at least one postbaseline evaluation.~Baseline values were carried forward for participants who discontinued before Week 48 due to lack of efficacy.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Mean Change From Baseline to Week 48 in HIV RNA | Black (n = 55, 16, 13) | -1.62 log10 copies/mL |
| Treatment Experienced - Failing Current Therapy | Mean Change From Baseline to Week 48 in HIV RNA | Non-Black ( n= 22, 6, 6) | -1.52 log10 copies/mL |
| Treatment Experienced - Treatment Intolerant | Mean Change From Baseline to Week 48 in HIV RNA | Black (n = 55, 16, 13) | -1.16 log10 copies/mL |
| Treatment Experienced - Treatment Intolerant | Mean Change From Baseline to Week 48 in HIV RNA | Non-Black ( n= 22, 6, 6) | -2.21 log10 copies/mL |
| Treatment Naive | Mean Change From Baseline to Week 48 in HIV RNA | Black (n = 55, 16, 13) | -2.49 log10 copies/mL |
| Treatment Naive | Mean Change From Baseline to Week 48 in HIV RNA | Non-Black ( n= 22, 6, 6) | -1.66 log10 copies/mL |
Secondary
Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48
Numbers of participants with HIV RNA copies \<400 copies/mL were summarized by race for each time point.
Time frame: Week 48
Population: Efficacy analyses were based on the Full Analysis Set population that included all participants who took at least one dose of study medication and had at least one postbaseline evaluation. The Treatment-Related Discontinuation = Failure approach was used as the primary method for handling missing HIV RNA values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Black (n = 69, 62, 14) | 51 Participants |
| Treatment Experienced - Failing Current Therapy | Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Non-Black (n = 25, 18, 7) | 17 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Black (n = 69, 62, 14) | 50 Participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Non-Black (n = 25, 18, 7) | 18 Participants |
| Treatment Naive | Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Black (n = 69, 62, 14) | 12 Participants |
| Treatment Naive | Number of Participants Who Achieved HIV RNA <400 Copies/mL at Week 48 | Non-Black (n = 25, 18, 7) | 5 Participants |
Secondary
Number 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: Week 48
Population: Efficacy analyses were based on the Full Analysis Set population that included all participants who took at least one dose of study medication and had at least one postbaseline evaluation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Experienced - Failing Current Therapy | Number of Participants Without Loss of Virologic Response | Black (n = 70, 69, 14) | 48 participants |
| Treatment Experienced - Failing Current Therapy | Number of Participants Without Loss of Virologic Response | Non-Black (n = 27, 19, 7) | 16 participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Without Loss of Virologic Response | Black (n = 70, 69, 14) | 49 participants |
| Treatment Experienced - Treatment Intolerant | Number of Participants Without Loss of Virologic Response | Non-Black (n = 27, 19, 7) | 17 participants |
| Treatment Naive | Number of Participants Without Loss of Virologic Response | Black (n = 70, 69, 14) | 11 participants |
| Treatment Naive | Number of Participants Without Loss of Virologic Response | Non-Black (n = 27, 19, 7) | 5 participants |