HIV Infections
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of 400 mg QD nevirapine extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR) in ARV therapy naïve HIV-1 infected patients after 48 weeks of treatment. Secondary objectives are to evaluate safety and pharmacokinetics of NVP XR and NVP IR.
Interventions
DRUGnevirapine IR
200 mg BID
DRUGnevirapine XR
400 mg QD
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent in accordance with Good Clinical Practice and local regulatory requirements prior to trial participation 2. HIV-1 infected males or females \>= 18 years of age with positive serology (ELISA) confirmed by Western blot 3. No previous antiretroviral treatment 4. Males with CD4+ counts \>50 - \<400 cells/ml or females with CD4+ counts \>50-\<250 cells/ml 5. Adequate renal function defined as a calculated creatinine clearance (CLCr) greater than or equal to 50 mL/min according to the Cockcroft-Gault formula as follows: Male: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) = CLCr (mL/min). Female: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) x 0.85 = CLCr (mL/min). 6. Karnofsky score \>70 (see Appendix 10.4) 7. An HIV-1 viral load of 1,000 copies/mL 8. Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent important opportunistic infections as defined in Appendix 10.2 9. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system (listed in Appendix 10.3) during the study. 10. For centers participating in the PK substudy only: Written informed consent in accordance with GCP and local legislation for participation in the PK substudy. Refusal to participate in the PK substudy is not an exclusion criterion for participation in the trial. Only study centers with previous experience and equipped in handling PK samples are eligible for participation in the substudy.
Exclusion criteria
1. Active drug abuse or chronic alcoholism at the investigator's discretion 2. Active hepatitis B or C disease, defined as HBsAg-positive and HBV-DNA-positive or HCV-RNA-positive 3. Female patients of child-bearing potential who: are pregnant at screening; are breast feeding; are planning to become pregnant; are not willing to use a barrier method of contraception, or; are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives Note: During participation in this study, females and males have to use barrier methods of contraception in addition or instead of ethinyl estradiol containing oral contraceptives. 4. Laboratory parameters \>DAIDS Grade 2 5. ALT/AST \> DAIDS Grade 1 6. Hypersensitivity to any ingredients of the test products 7. Previous use of Viramune® (nevirapine) or any other antiretroviral agents (does not include use of single dose NVP for the prevention of mother to child transmission) 8. Resistance to NNRTIs or either one of the components of Truvada® (emtricitabine or tenofovir disoproxil fumarate) or lamivudine (3TC) based on HIV-1 genotypic resistance testing report obtained at screening 9. Patients who are receiving other concomitant treatments which are not permitted, as described in the prescribing information 10. Use of investigational medications (any experimental agent other than the study regimen) within 30 days before study entry or during the trial 11. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2) 12. Patients who have been diagnosed with malignant disease 13. Patients who in the opinion of the investigator are not candidates for inclusion in the study 14. Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma 15. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | week 48 | Primary endpoint was the number of patients with a sustained virologic response through week 48 using LLOQ = 50 copies/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | week 0 to 144 | — |
| Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | week 0 to 144 | — |
| Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | week 144 | Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL |
| Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | week 0 to 144 | — |
| Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population | baseline, week 144 | — |
| Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population | baseline, week 144 | — |
| Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | until last patient completed 144 weeks (up to 193 weeks) | — |
| Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | week 0 to 72 | — |
| Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | week 0 to 72 | — |
| Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | week 0 to 72 | — |
| Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | week 0 to 72 | — |
| Relative Bioavailability Trough C_pre,ss,1 | week 132 | Relative bioavailability measured of trough concentrations. Analysis based on adjusted by-treatment geometric means, the adjusted geometric mean ratio of NVP XR : NVP IR and it's 90% confidence interval with p-value and the inter-individual geometric coefficient of variation. |
| Occurrence of Hepatic Events | until last patient completed 144 weeks (up to 193 weeks) | Frequency of patients with hepatitis symptoms |
| Occurrence of Rashes | until last patient completed 144 weeks (up to 193 weeks) | Frequency of patients with drug related rash events by functional grouping |
Countries
Argentina, Australia, Belgium, Botswana, Canada, France, Germany, Ireland, Italy, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, Russia, South Africa, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NVP IR 200mg QD Nevirapine immediate release 200 mg tablets given once daily | 0 |
| NVP IR 200mg BID Nevirapine immediate release 200 mg tablets given twice daily | 508 |
| NVP XR 400mg QD Nevirapine extended release 400 mg tablets given once daily | 505 |
| Total | 1,013 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 144-week Double-blind, Double-dummy | Adverse Event | 0 | 48 | 43 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Death | 0 | 6 | 3 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Lack of Efficacy | 0 | 36 | 33 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Lost to Follow-up | 0 | 15 | 12 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Not treated with study drug | 0 | 2 | 0 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Other | 0 | 8 | 11 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Pregnancy | 0 | 1 | 9 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Protocol Violation | 0 | 15 | 9 | 0 | 0 |
| 144-week Double-blind, Double-dummy | Withdrawal by Subject | 0 | 19 | 7 | 0 | 0 |
| 14 Day Lead-In Period | Adverse Event | 38 | 0 | 0 | 0 | 0 |
| 14 Day Lead-In Period | In/Exclusion criteria | 4 | 0 | 0 | 0 | 0 |
| 14 Day Lead-In Period | Lost to Follow-up | 4 | 0 | 0 | 0 | 0 |
| 14 Day Lead-In Period | Other | 5 | 0 | 0 | 0 | 0 |
| 14 Day Lead-In Period | Withdrawal by Subject | 4 | 0 | 0 | 0 | 0 |
| Open-Label Extension Period | Declined entry into extension period | 0 | 0 | 0 | 43 | 50 |
Baseline characteristics
| Characteristic | NVP IR 200mg BID | Total | NVP XR 400mg QD |
|---|---|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 9.7 | 38.1 years STANDARD_DEVIATION 9.7 | 38.3 years STANDARD_DEVIATION 9.7 |
| Age, Customized 18 to < 41 years | 316 participants | 615 participants | 299 participants |
| Age, Customized 41 to < 56 years | 165 participants | 347 participants | 182 participants |
| Age, Customized 56 to < 65 years | 25 participants | 44 participants | 19 participants |
| Age, Customized 65 years or more | 2 participants | 7 participants | 5 participants |
| Alcohol Status Drinks - could interfere with trial | 3 participants | 5 participants | 2 participants |
| Alcohol Status Drinks - no interfere with trial | 354 participants | 689 participants | 335 participants |
| Alcohol Status Non drinker | 151 participants | 319 participants | 168 participants |
| Gender Female | 75 participants | 149 participants | 74 participants |
| Gender Male | 433 participants | 864 participants | 431 participants |
| Race/Ethnicity, Customized American Indian / Alaskan Native | 6 participants | 14 participants | 8 participants |
| Race/Ethnicity, Customized Asian | 13 participants | 28 participants | 15 participants |
| Race/Ethnicity, Customized Black | 113 participants | 207 participants | 94 participants |
| Race/Ethnicity, Customized Hawaiian / Pacific Isle. | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic / Latino | 109 Participants | 224 Participants | 115 Participants |
| Race/Ethnicity, Customized Not Hispanic / Latino | 399 Participants | 789 Participants | 390 Participants |
| Race/Ethnicity, Customized White | 376 participants | 763 participants | 387 participants |
| Region of Enrollment Africa | 57 participants | 106 participants | 49 participants |
| Region of Enrollment Europe | 253 participants | 510 participants | 257 participants |
| Region of Enrollment Latin America | 49 participants | 107 participants | 58 participants |
| Region of Enrollment North America / Australia | 149 participants | 290 participants | 141 participants |
| Smoking History Current smoker | 177 participants | 372 participants | 195 participants |
| Smoking History Ex-smoker | 81 participants | 167 participants | 86 participants |
| Smoking History Never smoked | 250 participants | 474 participants | 224 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 308 / 1,068 | 131 / 191 | 403 / 505 | 271 / 315 | 81 / 315 |
| serious Total, serious adverse events | 20 / 1,068 | 33 / 191 | 93 / 505 | 50 / 315 | 9 / 315 |
Outcome results
Primary
Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Primary endpoint was the number of patients with a sustained virologic response through week 48 using LLOQ = 50 copies/mL
Time frame: week 48
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg BID | Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Responder | 384 participants |
| NVP IR 200mg BID | Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Non responder | 122 participants |
| NVP XR 400mg QD | Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Responder | 409 participants |
| NVP XR 400mg QD | Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Non responder | 96 participants |
p-value: <0.000195% CI: [-0.1, 10]Cochran's statistic
Secondary
Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population
Time frame: baseline, week 144
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication; descriptive analysis uses the imputation method: last observation carried forward; statistical analysis uses observed cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NVP IR 200mg BID | Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population | 239.3 cells/cubic millimeter | Standard Deviation 171.4 |
| NVP XR 400mg QD | Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population | 270.7 cells/cubic millimeter | Standard Deviation 183.1 |
p-value: 0.007895% CI: [8.67, 57.06]ANCOVA
Secondary
Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population
Time frame: baseline, week 144
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication; descriptive analysis uses the imputation method: last observation carried forward; statistical analysis uses observed cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NVP IR 200mg BID | Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population | -2.7 log10 copies/mL | Standard Deviation 0.9 |
| NVP XR 400mg QD | Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population | -2.8 log10 copies/mL | Standard Deviation 0.8 |
p-value: 0.771995% CI: [-0.08, 0.06]ANCOVA
Secondary
Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events
Time frame: week 0 to 72
Population: Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 4 to <6 | 0.012 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 24 to <32 | 0.026 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 8 to <12 | 0.024 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 32 to <40 | 0.026 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 40 to <48 | 0.029 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 12 to <16 | 0.026 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 48 to <60 | 0.029 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 6 to <8 | 0.022 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 60 to <72 | 0.032 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 16 to <24 | 0.026 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week >=72 | 0.038 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week >=72 | 0.026 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 2 to <4 | 0.002 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 4 to <6 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 6 to <8 | 0.016 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 8 to <12 | 0.018 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 12 to <16 | 0.018 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 16 to <24 | 0.018 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 24 to <32 | 0.020 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 32 to <40 | 0.022 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 40 to <48 | 0.022 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 48 to <60 | 0.022 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events | Interval Week 60 to <72 | 0.022 cumulative probability |
Secondary
Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities
Time frame: week 0 to 72
Population: Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 4 to <6 | 0.012 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 24 to <32 | 0.067 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 8 to <12 | 0.059 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 32 to <40 | 0.070 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 40 to <48 | 0.076 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 12 to <16 | 0.063 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 48 to <60 | 0.076 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 6 to <8 | 0.049 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 60 to <72 | 0.076 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 16 to <24 | 0.063 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week >=72 | 0.076 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week >=72 | 0.070 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 2 to <4 | 0.002 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 4 to <6 | 0.014 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 6 to <8 | 0.026 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 8 to <12 | 0.034 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 12 to <16 | 0.036 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 16 to <24 | 0.036 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 24 to <32 | 0.043 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 32 to <40 | 0.049 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 40 to <48 | 0.056 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 48 to <60 | 0.058 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities | Interval Week 60 to <72 | 0.058 cumulative probability |
Secondary
Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities
Time frame: week 0 to 72
Population: Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 4 to <6 | 0.006 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 24 to <32 | 0.042 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 8 to <12 | 0.033 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 32 to <40 | 0.044 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 40 to <48 | 0.053 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 12 to <16 | 0.039 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 48 to <60 | 0.053 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 6 to <8 | 0.027 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 60 to <72 | 0.053 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 16 to <24 | 0.039 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week >=72 | 0.053 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week >=72 | 0.033 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 4 to <6 | 0.002 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 6 to <8 | 0.006 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 8 to <12 | 0.008 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 12 to <16 | 0.008 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 16 to <24 | 0.008 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 24 to <32 | 0.015 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 32 to <40 | 0.019 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 40 to <48 | 0.028 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 48 to <60 | 0.031 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities | Interval Week 60 to <72 | 0.033 cumulative probability |
Secondary
Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash
Time frame: week 0 to 72
Population: Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 16 to <24 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 6 to <8 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 24 to <32 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 32 to <40 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 8 to <12 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 40 to <48 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 4 to <6 | 0.002 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 48 to <60 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 60 to <72 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 12 to <16 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week >=72 | 0.004 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week >=72 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 4 to <6 | 0.006 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 6 to <8 | 0.008 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 8 to <12 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 12 to <16 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 16 to <24 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 24 to <32 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 32 to <40 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 40 to <48 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 60 to <72 | 0.010 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash | Interval Week 48 to <60 | 0.010 cumulative probability |
Secondary
Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication
Time frame: week 0 to 144
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 4 to <6 | 0.034 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 6 to <8 | 0.067 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 8 to <12 | 0.081 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 12 to <16 | 0.093 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 16 to <24 | 0.113 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 24 to <32 | 0.130 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 32 to <40 | 0.156 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 40 to <48 | 0.172 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 48 to <60 | 0.192 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 60 to <72 | 0.202 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 72 to <84 | 0.213 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 84 to <96 | 0.229 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 96 to <108 | 0.243 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 108 to <120 | 0.267 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 120 to <132 | 0.275 cumulative probability |
| NVP IR 200mg QD | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 132 to <144 | 0.289 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 84 to <96 | 0.206 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 0 to <2 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 40 to <48 | 0.156 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 2 to <4 | 0.000 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 132 to <144 | 0.244 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 4 to <6 | 0.026 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 48 to <60 | 0.162 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 6 to <8 | 0.046 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 96 to <108 | 0.218 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 8 to <12 | 0.059 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 60 to <72 | 0.176 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 12 to <16 | 0.067 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 120 to <132 | 0.236 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 16 to <24 | 0.083 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 72 to <84 | 0.188 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 24 to <32 | 0.115 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 108 to <120 | 0.232 cumulative probability |
| NVP IR 200mg BID | Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication | Interval Week 32 to <40 | 0.139 cumulative probability |
Secondary
Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population
Time frame: week 0 to 144
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 12 to <16 | 0.029 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 48 to <60 | 0.047 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 6 to <8 | 0.023 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 60 to <72 | 0.052 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 16 to <24 | 0.031 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 72 to <84 | 0.054 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 4 to <6 | 0.006 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 84 to <96 | 0.054 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 24 to <32 | 0.04 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 96 to <108 | 0.057 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 8 to <12 | 0.029 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 108 to <120 | 0.057 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 32 to <40 | 0.042 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 120 to <132 | 0.06 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 2 to <4 | 0.006 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 132 to <144 | 0.06 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 40 to <48 | 0.047 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 144 to <168 | 0.062 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 0 to <2 | 0 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 144 to <168 | 0.047 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 0 to <2 | 0 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 2 to <4 | 0.002 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 4 to <6 | 0.006 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 6 to <8 | 0.008 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 8 to <12 | 0.01 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 12 to <16 | 0.019 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 16 to <24 | 0.021 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 24 to <32 | 0.025 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 32 to <40 | 0.025 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 40 to <48 | 0.027 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 48 to <60 | 0.027 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 60 to <72 | 0.032 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 72 to <84 | 0.035 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 84 to <96 | 0.04 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 96 to <108 | 0.04 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 108 to <120 | 0.045 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 120 to <132 | 0.047 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population | Interval Week 132 to <144 | 0.047 proportion of participants |
Secondary
Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Time frame: week 0 to 144
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 12 to <16 | 0.832 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 48 to <60 | 0.777 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 6 to <8 | 0.834 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 60 to <72 | 0.759 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 16 to <24 | 0.83 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 72 to <84 | 0.733 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 4 to <6 | 0.838 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 84 to <96 | 0.713 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 24 to <32 | 0.822 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 96 to <108 | 0.686 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 8 to <12 | 0.834 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 108 to <120 | 0.662 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 32 to <40 | 0.806 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 120 to <132 | 0.65 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 2 to <4 | 0.84 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 132 to <144 | 0.63 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 40 to <48 | 0.792 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 144 to <168 | 0.61 proportion of participants |
| NVP IR 200mg BID | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 0 to <2 | 1 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 144 to <168 | 0.66 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 0 to <2 | 1 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 2 to <4 | 0.865 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 4 to <6 | 0.865 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 6 to <8 | 0.865 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 8 to <12 | 0.863 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 12 to <16 | 0.861 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 16 to <24 | 0.859 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 24 to <32 | 0.848 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 32 to <40 | 0.832 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 40 to <48 | 0.816 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 48 to <60 | 0.808 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 60 to <72 | 0.788 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 72 to <84 | 0.766 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 84 to <96 | 0.745 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 96 to <108 | 0.719 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 108 to <120 | 0.697 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 120 to <132 | 0.681 proportion of participants |
| NVP XR 400mg QD | Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Interval Week 132 to <144 | 0.671 proportion of participants |
Secondary
Occurrence of Elevations in Laboratory Measurement by DAIDS Grade
Time frame: until last patient completed 144 weeks (up to 193 weeks)
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 4 AEs | 17 participants |
| NVP IR 200mg QD | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 3 or 4 AEs | 53 participants |
| NVP IR 200mg BID | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 3 or 4 AEs | 111 participants |
| NVP IR 200mg BID | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 4 AEs | 25 participants |
| NVP XR 400mg QD | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 3 or 4 AEs | 71 participants |
| NVP XR 400mg QD | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 4 AEs | 11 participants |
| XR-IR/XR | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 4 AEs | 3 participants |
| XR-IR/XR | Occurrence of Elevations in Laboratory Measurement by DAIDS Grade | DAIDS grade 3 or 4 AEs | 8 participants |
Secondary
Occurrence of Hepatic Events
Frequency of patients with hepatitis symptoms
Time frame: until last patient completed 144 weeks (up to 193 weeks)
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVP IR 200mg QD | Occurrence of Hepatic Events | 10 participants |
| NVP IR 200mg BID | Occurrence of Hepatic Events | 8 participants |
| NVP XR 400mg QD | Occurrence of Hepatic Events | 2 participants |
| XR-IR/XR | Occurrence of Hepatic Events | 0 participants |
Secondary
Occurrence of Rashes
Frequency of patients with drug related rash events by functional grouping
Time frame: until last patient completed 144 weeks (up to 193 weeks)
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg QD | Occurrence of Rashes | rash group III | 3 participants |
| NVP IR 200mg QD | Occurrence of Rashes | rash group II | 6 participants |
| NVP IR 200mg QD | Occurrence of Rashes | rash group IV | 0 participants |
| NVP IR 200mg QD | Occurrence of Rashes | rash group IIA | 4 participants |
| NVP IR 200mg QD | Occurrence of Rashes | rash group I | 9 participants |
| NVP IR 200mg BID | Occurrence of Rashes | rash group IIA | 5 participants |
| NVP IR 200mg BID | Occurrence of Rashes | rash group III | 5 participants |
| NVP IR 200mg BID | Occurrence of Rashes | rash group IV | 0 participants |
| NVP IR 200mg BID | Occurrence of Rashes | rash group II | 13 participants |
| NVP IR 200mg BID | Occurrence of Rashes | rash group I | 11 participants |
| NVP XR 400mg QD | Occurrence of Rashes | rash group IIA | 1 participants |
| NVP XR 400mg QD | Occurrence of Rashes | rash group I | 6 participants |
| NVP XR 400mg QD | Occurrence of Rashes | rash group II | 3 participants |
| NVP XR 400mg QD | Occurrence of Rashes | rash group III | 0 participants |
| NVP XR 400mg QD | Occurrence of Rashes | rash group IV | 0 participants |
| XR-IR/XR | Occurrence of Rashes | rash group III | 0 participants |
| XR-IR/XR | Occurrence of Rashes | rash group II | 0 participants |
| XR-IR/XR | Occurrence of Rashes | rash group I | 0 participants |
| XR-IR/XR | Occurrence of Rashes | rash group IIA | 0 participants |
| XR-IR/XR | Occurrence of Rashes | rash group IV | 0 participants |
Secondary
Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL
Time frame: week 144
Population: Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NVP IR 200mg BID | Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Responder | 296 participants |
| NVP IR 200mg BID | Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Non responder | 210 participants |
| NVP XR 400mg QD | Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Responder | 321 participants |
| NVP XR 400mg QD | Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population | Non responder | 184 participants |
p-value: <0.000195% CI: [-1.11, 10.79]Cochran's statistic
Secondary
Relative Bioavailability Trough C_pre,ss,1
Relative bioavailability measured of trough concentrations. Analysis based on adjusted by-treatment geometric means, the adjusted geometric mean ratio of NVP XR : NVP IR and it's 90% confidence interval with p-value and the inter-individual geometric coefficient of variation.
Time frame: week 132
Population: Only patients with trough drawn PK time window (12+/-2.5 hr for IR; 24+/-5hr for XR) at week 132 are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NVP IR 200mg QD | Relative Bioavailability Trough C_pre,ss,1 | 4567.03 ng/mL | Geometric Coefficient of Variation 49.9 |
| NVP IR 200mg BID | Relative Bioavailability Trough C_pre,ss,1 | 3634.26 ng/mL | Geometric Coefficient of Variation 49.9 |
Comparison: adjusted geometric mean ratio NVP XR : NVP IRp-value: 0.554290% CI: [74.62, 84.86]ANOVA