HIV-1 Infection
Conditions
Keywords
HIV, AIDS, Immunodeficiency Virus, Human, PREZISTA, darunavir, TMC114, TMC125, Protease Inhibitor, Non-Nucleoside Reverse Transcriptase Inhibitor, Truvada, Treatment Naive
Brief summary
The purpose of this study is to determine the pharmacokinetic profile of TMC125 400mg with tenofovir DF/emtricitabine FDC (fixed dose combination) 300/200mg all dosed once daily with and without darunavir/ritonavir 800/100 mg once daily in HIV-1 infected, antiretroviral (ARV) naÃ-ve patients (patients who have never received ARV treatment).
Detailed description
This is a multi-center, open-label (doctors and patients know which drug is being given), Phase IIa clinical trial to evaluate the pharmacokinetic (PK) profile, safety and tolerability of TMC125 dosed once daily with tenofovir/emtricitabine with and without darunavir/ritonavir in antiretroviral naive HIV-1 infected patients. There will be an optional open-label extension phase to evaluate effectiveness, safety and tolerability of continued tenofovir/emtricitabine with darunavir/ritonavir all dosed once daily for 48 weeks. This study will be conducted in the United States at up to 5 sites where 20 patients will initially receive TMC125 400mg with tenofovir DF/emtricitabine FDC 300/200 mg all dosed once daily for 14 days. On Day 15, a blood sample will be obtained and intensive TMC125 pharmacokinetic (PK) values and fasting lipids (check of total cholesterol, direct LDL, HDL, triglycerides) following a 10 hour fast (no eating) will be assessed. Patients will then add darunavir / ritonavir 800/100 mg once a day to the regimen for Days 15 - 29. On Day 29 intensive PK sampling for TMC125, darunavir and ritonavir will be performed and fasting lipids will be evaluated. On Day 29, patients will discontinue TMC125 and continue darunavir/ritonavir 800/100 mg and tenofovir DF/emtricitabine FDC 300/200 mg all dosed once daily. On Day 43, fasting lipids will be assessed. At this point, patients may enter the optional open-label extension phase of the study and continue treatment with darunavir/ritonavir 800mg/100 mg and tenofovir DF/emtricitabine FDC 300/200mg all dosed once daily through 48 total weeks of treatment. The study will consist of a total of 8 visits including 2 intensive PK visits. Within 4 weeks after the Screening Visit, the study site should have received all data to determine a patient's eligibility for the study. The Baseline Visit (Day 1) will be followed by a study visit on Day 8. An intensive PK visit will occur on Day 15. After modification of therapy on Day 15, a study visit will occur on Day 22. A second intensive PK visit will occur on Day 29. On Day 43 a study visit will occur at which point study therapy will be discontinued unless the patient elects to continue in the optional open label extension phase of the study. Patients electing to continue in the open-label extension will have 4 additional study visits at Week 12, 24, 36 and 48. All patients will be asked to return for a 4-week follow-up visit after the completion of study treatment. During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for effectiveness and safety will be done at regular visits as well as blood pressure monitoring. All patients will receive TMC125 400 mg orally (by mouth) once daily. Tenofovir DF 300mg/emtricitabine 200mg will be dosed once daily orally as the fixed dose combination. Darunavir/ritonavir will be dosed 800/100 mg orally once daily. All doses should be administered following a meal.
Interventions
DRUGTMC125; darunavir; ritonavir
TMC125 400mg once daily for 4 weeks; Darunavir-800mg once daily for 48 weeks; Ritonavir-100mg once daily for 48 weeks
Sponsors
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Tibotec, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented HIV-1 infection * Naive to antiretroviral therapy (never received antiretroviral therapy prior to study) * In the opinion of the investigator, have an indication for antiretroviral therapy * Able to comply with the protocol requirements
Exclusion criteria
* No previous or current use of antiretroviral medications (ARVs) for the treatment of HIV infection or hepatitis B/C infection with anti-HIV activity * No evidence of antiretroviral resistance on current or past resistance assays * No chronic hepatitis B and/or C co-infection * No grade 3 or 4 laboratory abnormality as defined by National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) grading tables, or a calculated creatinine clearance (CLCr) \< 50 mL/min. * No known diabetes mellitus or hyperlipidemia requiring lipid-lowering therapy * No acute viral hepatitis including, but not limited to A, B, or C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av | 6 weeks | At visit Days 14 & 28, samples were collected pre-dose and at 1, 2, 3, 4, 6, 9, and 12 hours post-dose. An additional sample was taken at 24 hours (Day 15 or 29 as applicable) post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Day 1 through 42 and Week 48 | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia. Worst Grade is based on the DAIDS toxicity grading scale 0-5: No Toxicity-Death. |
| Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Day 1 through 42 and Week 48 | Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin. Normal Range: 3.0 - 27.0 ulU/mL |
| Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Day 1 through 42 and Week 48 | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death. |
| Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Day 1 through 42 and Week 48 | Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density lipoprotein (HDL). Normal Range: 40 - 59 mG/dL 1.03 - 1.53 mmol/L |
| Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Day 1 through 42 and Week 48 | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density lipoprotein (LDL) Direct. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death. |
| Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Day 1 through 42 and Week 48 | Number of Participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia. Worst Grade is based on the National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity grading scale, 0,1,2,3,4 and 5 : None, Mild, Moderate, Severe, Life-threatening and Death. |
| Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Day 8, 14, 22, 28, 42 and Week 48 | Virologic Response \< 50 HIV-1 RNA Copies/mL (ITT-Observed Case). |
| Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Baseline, Day 8, 14, 22, 28 & 42 and Week 48 | Log10 Viral Load (HIV-1 RNA copies/mL): Mean Changes From Baseline(ITT-Observed Case). |
| CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Baseline, Day 8, 14, 22, 28 & 42 ans Week 48 | CD4+ Cell Count (x 10\^6 cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case). |
| CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Baseline, Day 8, 14, 22, 28 & 42 and Week 48 | — |
| Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Day 1 through 48 and Week 48 | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death. |
Participant flow
Recruitment details
The 42-day open-label main treatment phase of this trial was conducted from 10 December 2007 to 27 May 2008. Four investigators from the US participated in this multicenter trial. A total of 35 subjects were screened and of these, 23 subjects entered the trial and started the first treatment phase
Participants by arm
| Arm | Count |
|---|---|
| TDF/FTC +/- TMC125 +/- DRV/Rtv In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed.
In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed.
In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed.
Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Optional Extension: DRV/Rtv + TDF/FTC | Lost to Follow-up | 2 |
| Optional Extension: DRV/Rtv + TDF/FTC | Physician Decision | 1 |
| Optional Extension: DRV/Rtv + TDF/FTC | Pregnancy | 1 |
| Treatment A: TMC125 + TDF/FTC | Lost to Follow-up | 1 |
| Treatment A: TMC125 + TDF/FTC | Physician Decision | 1 |
| Treatment C: DRV/Rtv + TDF/FTC | Physician Decision | 1 |
Baseline characteristics
| Characteristic | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 35.87 years STANDARD_DEVIATION 13.264 |
| Body Mass Index | 26.33 kg/m2 STANDARD_DEVIATION 4.629 |
| CYP2C19 Genotyping CYP2C19*17/CYP2C19*17 : Ultrarapid Phenotype | 1 participants |
| CYP2C19 Genotyping CYP2C19*17/CYP2C19*2 : Normal Phenotype | 2 participants |
| CYP2C19 Genotyping CYP2C19*1/CYP2C19*17 : Rapid Phenotype | 5 participants |
| CYP2C19 Genotyping CYP2C19*1/CYP2C19*1 : Normal Phenotype | 5 participants |
| CYP2C19 Genotyping CYP2C19*1/CYP2C19*2 : Intermediate Phenotype | 7 participants |
| CYP2C19 Genotyping CYP2C19*2/CYP2C19*2 : Poor Phenotype | 1 participants |
| CYP2C19 Genotyping No data | 2 participants |
| CYP2C9 Genotyping CYP2C9*1/CYP2C1*1 : Normal Phenotype | 19 participants |
| CYP2C9 Genotyping CYP2C9*1/CYP2C1*3 : Intermediate Phenotype | 2 participants |
| CYP2C9 Genotyping No data | 2 participants |
| Family History Related to Skin Disease No | 18 participants |
| Family History Related to Skin Disease Yes | 5 participants |
| Height | 172.73 cm STANDARD_DEVIATION 8.405 |
| Race/Ethnicity, Customized Black | 9 participants |
| Race/Ethnicity, Customized Caucasian / White | 9 participants |
| Race/Ethnicity, Customized Hispanic | 5 participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 20 Participants |
| Weight | 78.58 kg STANDARD_DEVIATION 13.711 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 23 | 9 / 21 | 4 / 21 | 13 / 18 |
| serious Total, serious adverse events | 0 / 23 | 0 / 21 | 0 / 21 | 1 / 18 |
Outcome results
Primary
Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av
At visit Days 14 & 28, samples were collected pre-dose and at 1, 2, 3, 4, 6, 9, and 12 hours post-dose. An additional sample was taken at 24 hours (Day 15 or 29 as applicable) post-dose.
Time frame: 6 weeks
Population: Intention To Treat (ITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av | 23 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av | 21 participants |
Comparison: Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.90% CI: [82.77, 110.1]Mixed Models Analysis (Cmin)
Comparison: Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.90% CI: [92.91, 113.3]Mixed Models Analysis (Cmax)
Comparison: Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.90% CI: [89.23, 109.8]Mixed Models Analysis (AUC24)
Comparison: Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means.90% CI: [89.39, 110.3]Mixed Models Analysis (Css,av)
Secondary
CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case)
Time frame: Baseline, Day 8, 14, 22, 28 & 42 and Week 48
Population: ITT (Observed)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Baseline (n=23) | 26.2 Percent Change from Baseline |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 8 (n=20) | 0.1 Percent Change from Baseline |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 14 (n=20) | 4.2 Percent Change from Baseline |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 22 (n=20) | 1.8 Percent Change from Baseline |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 28 (n=21) | 3.0 Percent Change from Baseline |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 42 (n=19) | 4.2 Percent Change from Baseline |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) | Week 48 (n=14) | 3.8 Percent Change from Baseline |
Secondary
CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case)
CD4+ Cell Count (x 10\^6 cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case).
Time frame: Baseline, Day 8, 14, 22, 28 & 42 ans Week 48
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Baseline (n=23) | 403.0 x 10^6 cell/L |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 8 (n=20) | 45.5 x 10^6 cell/L |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 14 (n=20) | 94.0 x 10^6 cell/L |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 22 (n=20) | 59.0 x 10^6 cell/L |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 28 (n=21) | 62.0 x 10^6 cell/L |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Day 42 (n=19) | 56.0 x 10^6 cell/L |
| Treatment A: TMC125 + TDF/FTC | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) | Week 48 (n=14) | 160.0 x 10^6 cell/L |
Secondary
Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case)
Log10 Viral Load (HIV-1 RNA copies/mL): Mean Changes From Baseline(ITT-Observed Case).
Time frame: Baseline, Day 8, 14, 22, 28 & 42 and Week 48
Population: ITT (Observed)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Day 14 (n=21) | -1.71 copies/mL | Standard Error 0.09 |
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Baseline (n=23) | 4.19 copies/mL | Standard Error 0.157 |
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Day 8 (n=19) | -1.41 copies/mL | Standard Error 0.094 |
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Day 22 (n=19) | -1.77 copies/mL | Standard Error 0.094 |
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Day 28 (n=20) | -1.86 copies/mL | Standard Error 0.123 |
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Day 42 (n=20) | -2.04 copies/mL | Standard Error 0.127 |
| Treatment A: TMC125 + TDF/FTC | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) | Week 48 (n=13) | -2.30 copies/mL | Standard Error 0.237 |
Secondary
Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia
Number of Participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia. Worst Grade is based on the National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity grading scale, 0,1,2,3,4 and 5 : None, Mild, Moderate, Severe, Life-threatening and Death.
Time frame: Day 1 through 42 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 1 | 1 participants |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 2 | 1 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 1 | 2 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 1 | 0 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 2 | 1 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 1 | 2 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia | Grade 2 | 1 participants |
Secondary
Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia. Worst Grade is based on the DAIDS toxicity grading scale 0-5: No Toxicity-Death.
Time frame: Day 1 through 42 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 1 | 0 participants |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 2 | 1 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 1 | 2 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 1 | 0 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 2 | 0 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 1 | 1 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia | Grade 2 | 0 participants |
Secondary
Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density lipoprotein (LDL) Direct. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.
Time frame: Day 1 through 42 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 1 | 0 participants |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 1 | 0 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 1 | 1 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 2 | 1 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 1 | 1 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct | Grade 2 | 1 participants |
Secondary
Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.
Time frame: Day 1 through 42 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 1 | 0 participants |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 1 | 0 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 1 | 2 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 2 | 0 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 1 | 1 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral | Grade 2 | 0 participants |
Secondary
Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.
Time frame: Day 1 through 48 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 1 | 0 participants |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 2 | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 1 | 0 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 1 | 0 participants |
| Treatment C | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 2 | 0 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 1 | 0 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides | Grade 2 | 0 participants |
Secondary
Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin
Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin. Normal Range: 3.0 - 27.0 ulU/mL
Time frame: Day 1 through 42 and Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Below 3.0 ulU/mL | 1 participant |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Above 27.0 ulU/mL | 1 participant |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Above 27.0 ulU/mL | 3 participant |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Below 3.0 ulU/mL | 2 participant |
| Treatment C | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Below 3.0 ulU/mL | 1 participant |
| Treatment C | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Above 27.0 ulU/mL | 2 participant |
| Optional Extension | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Below 3.0 ulU/mL | 1 participant |
| Optional Extension | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin | Above 27.0 ulU/mL | 3 participant |
Secondary
Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL)
Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density lipoprotein (HDL). Normal Range: 40 - 59 mG/dL 1.03 - 1.53 mmol/L
Time frame: Day 1 through 42 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Below 40 mG/dL (1.03 mmol/L) | 4 participants |
| Treatment A: TMC125 + TDF/FTC | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Above 59 mG/dL (1.53 mmol/L) | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Above 59 mG/dL (1.53 mmol/L) | 0 participants |
| Treatment B: TMC125 + TDF/FTC + DRV/Rtv | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Below 40 mG/dL (1.03 mmol/L) | 8 participants |
| Treatment C | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Below 40 mG/dL (1.03 mmol/L) | 6 participants |
| Treatment C | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Above 59 mG/dL (1.53 mmol/L) | 0 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Below 40 mG/dL (1.03 mmol/L) | 2 participants |
| Optional Extension | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) | Above 59 mG/dL (1.53 mmol/L) | 1 participants |
Secondary
Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case)
Virologic Response \< 50 HIV-1 RNA Copies/mL (ITT-Observed Case).
Time frame: Day 8, 14, 22, 28, 42 and Week 48
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: TMC125 + TDF/FTC | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Day 8 (n=19) | 0 participants |
| Treatment A: TMC125 + TDF/FTC | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Day 14 (n=21) | 3 participants |
| Treatment A: TMC125 + TDF/FTC | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Day 22 (n=19) | 4 participants |
| Treatment A: TMC125 + TDF/FTC | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Day 28 (n=20) | 6 participants |
| Treatment A: TMC125 + TDF/FTC | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Day 42 (n=20) | 7 participants |
| Treatment A: TMC125 + TDF/FTC | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) | Week 48 (n=13) | 10 participants |