BMS-Reyataz Study in Treatment in Naive Subjects to Compare the Efficacy and Safety Between Boosted Reyataz and Kaletra When in Combination With Fixed Dose Truvada
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00272779
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability and antiviral effects of atazanavir (ATV) plus ritonavir (RTV) versus a combination drug of lopinavir (LPV) plus RTV. A combination drug containing tenofovir (TDF) and emtricitabine (FTC) will also be taken by participants in both arms.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1057
- HIV RNA ≥5000 c/ml
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Any antiretroviral therapy within 30 days prior to screening;
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Women of Childbearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after the study;
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WOCBP using a prohibited contraceptive method
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WOCBP who are pregnant or breastfeeding;
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Women with a positive pregnancy test on enrollment or prior to study drug administration;
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Presence of a newly diagnosed HIV-Related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment;
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Suspected primary (acute) HIV infection;
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Prior antiviral therapy (>30 days of NRTI and/or >7 days of non-nucleoside reverse transcriptase inhibitor (NNRTI) or PI therapies) or any antiretroviral therapy within 30 days prior to screening; some exceptions are allowed for ARV therapy in use for Mother-to-child transmission;
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Participants with Cushing's syndrome;
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Untreated hypothyroidism or hyperthyroidism. A participant who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the thyroid stimulating hormone (TSH) performed within 30 days of screening is within normal drug range;
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Recent therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start or expected need for such therapy at the time of enrollment; or therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect CYP3A4;
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Participants with obstructive liver disease;
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Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis;
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Proven or suspected acute hepatitis in the 30 days prior to study entry;
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Intractable diarrhea (≥6 loose stools/day for at least 7 consecutive days) within 30 days prior to study entry;
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Inability to swallow capsules;
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Active peripheral neuropathy;
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Presence of cardiomyopathy (due to any cause) or any significant cardiovascular disease, such as unstable ischemic heart disease;
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Known, clinically significant cardiac conduction system disease.
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Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:
- calculated creatine clearance <60 mL/min as estimated by the Cockcroft-Gault equation;
- total serum lipase ≥ 1.4 times the upper limit of normal;
- liver enzymes (AST, ALT) ≥ 5 times the upper limit of normal;
- total serum bilirubin ≥ 1.5 times the upper limit of normal.
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Hypersensitivity to any component of the formulation of study drug;
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Prohibited therapies;
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Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for study or unable to comply with the dosing requirements;
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Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lopinavir (LPV) + RTV Tenofovi-Emtricitabine (TDF/FTC) tablet Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks. Lopinavir (LPV) + RTV LPV Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks. Atazanavir (ATV) + Ritonovir (RTV) ATV Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks. Atazanavir (ATV) + Ritonovir (RTV) RTV Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks. Atazanavir (ATV) + Ritonovir (RTV) Tenofovi-Emtricitabine (TDF/FTC) tablet Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks. Lopinavir (LPV) + RTV RTV Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
- Primary Outcome Measures
Name Time Method Area Under the Concentration-time Curve, in One Dosing Interval [AUC(TAU)] of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. AUC(TAU) was derived from the plasma concentration versus time data. It was calculated from time 0 to 12 hours for LPV and RTV in the LPV/RTV regimen, 0-24 hours for ATV and RTV in the ATV/RTV regimen, and 0-24 hours for tenofovir in both regimens at Week 4.
AUC (0-24) of RTV at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. AUC (0-24) was derived from plasma concentration versus time data. It was estimated as 2 times the AUC(TAU) based on 12-hour PK.
Cmin of Tenofovir at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. Cmin was derived from plasma concentration versus time data.
Mean Change From Baseline in Subcutaneous Adipose Tissue (SAT)-To-Trunk Adipose Tissue (TAT) Ratio Associated With CCDC122_5980 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. SAT and TAT were measured by computed tomography (CT).
Maximum Plasma Concentration (Cmax) of ATV/RTV and LPV/RTV in the Presence of an Antiretroviral (ARV) Regimen Including TDF at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given every day (QD) and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given twice daily (BID) and TDF given QD. Cmax was derived from plasma concentration versus time data.
Terminal Elimination Half-life (T-half) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. T-half was derived from the plasma concentration versus time data.
Inhibitory Quotient (IQ) of ATV and LPV When Dosed With RTV at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. IQ defined as Cmin at week 4 divided by protein binding adjusted EC90 values for the respective protease inhibitor (ATV or LPV) derived from individual participant clinical isolates.
Cmin of RTV at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. Cmin was derived from plasma concentration versus time data.
Mean Change From Baseline in Trunk-to-Limb Fat Ratio as Measured by Dual Energy X-ray Absorptiometry (DEXA) at Week 96 Baseline (Day 1) and Week 96. Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_598 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Protein Binding Adjusted Effective Concentration (EC-90) of ATV and LPV When Dosed With RTV at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. EC90/50=concentration of drug inducing 90%/50% of its maximal response. Protein binding adjusted EC90 for ATV and LPV were derived from phenotypically measured individual EC50 values at baseline using the following formula: Protein binding adjusted EC90 (ng/mL) = scale factor × molecular weight of the free base × EC50 micrometer(μM)/ unbound fraction (fu). Scale factor relates EC50 to EC90 (value of 3 and 2 for ATV and LPV, respectively); fu: estimated unbound fraction of ATV and LPV in vivo (0.14 and 0.02 for ATV and LPV respectively).
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_097 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Asssociated With RS11030679 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Visceral Adipose Tissue (VAT) Associated With BRUNOL_1842 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. VAT was measured by computed tomography (CT).
Mean Change From Baseline in VAT Associated With RETN_730 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. VAT was measured by computed tomography (CT).
Mean Change From Baseline in VAT-to-TAT Ratio Associated With CCDA122_5980 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. VAT and TAT were measured by computed tomography (CT).
Number of Participants With Human-immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) < 50 Copies (c)/mL at Week 48 Baseline (Day 1) and Week 48 HIV RNA \< 50 c/mL is the most stringent measure of viral suppression (lowest threshold of assay) and indicates that a participant responded to treatment.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. Tmax was derived from the plasma concentration versus time data.
Cmax of Tenofovir at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. Cmax was derived from plasma concentration versus time data.
AUC (TAU) of Tenofovir at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. AUC (TAU) was derived from plasma concentration versus time data.It was calculated from time 0-24 hours for tenofovir in LPV/RPV and ATV/RTV regimen at Week 4.
Mean Change From Baseline in Fasting Non-High Density Lipoprotein (HDL) Cholesterol Associated With RETN_097 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted (adj) p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_2265 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Triglycerides Associated With APOE_C130R Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_734 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Plasminogen Activator Inhibitor (PAI)-1 Associated With APOE_R176C Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Associated With IL6_5309 Baseline (Day 1), Week 48, and Week 96. The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Minimum Plasma Concentration (Cmin) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. Cmin was derived from the plasma concentration versus time data.
Cmax of RTV at Week 4 Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD. Cmax was derived from plasma concentration versus time data.
Number of Participants With Single Nucleotide Polymorphisms (SNPs) Included in Genotype-Phenotype Analysis Baseline visit 19 genes of interest were selected from previous results or literature, and 34 SNPs were genotyped. Phenotype-Genotype analysis was performed using 31 of the SNPs. The genotypes of each SNP were further classified as either a minor allele carrier (MAC) group composed of heterozygous and rare homozygous genotypes, or wild type \[WT, common homozygous\].
- Secondary Outcome Measures
Name Time Method Number of Participants With HIV RNA < 400 c/mL at Week 48 Baseline (Day 1) and Week 48 HIV RNA \< 400 c/mL is a less stringent measure of viral suppression (highest threshold of assay) and indicates that a participant responded to treatment.
Mean Change in Fasting Lipid at Week 48 Baseline (Day 1) and Week 48. Mean change from baseline in fasting lipids, for fasting total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, and triglycerides at Week 48 were determined.
Number of Participants With Laboratory Abnormalities in Serum Enzymes Levels Through Week 48 At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Laboratory measurements marked as abnormal, as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria in serum enzymes were: Creatine phosphokinase (CPK): Grade 3: 5.1 - 10.0 \* upper limit of normal (ULN), Grade 4: \>10\* ULN; Lipase: Grade 3: 2.10 - 5.0\* ULN, Grade 4: 5.0\* ULN.
Number of Participants With Laboratory Abnormalities in Liver Function Test Through Week 48 At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Liver function tests abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), while albumin was graded as per National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE). Grade 3 and 4 criteria were: alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase: Grade 3: 5.1- 10\*ULN, Grade 4: \>10\*ULN; direct and total bilirubin: Grade 3: 2.6- 5\*ULN, Grade 4: \>5\*ULN, Albumin: Grade 3: \<2g/dL.
Number of Participants With Laboratory Abnormalities in Renal Function Test Through Week 48 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, and 48. Renal function test abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: Blood urea nitrogen (BUN): Grade 3: 5.1- 10\*ULN, Grade 4: \>10\*ULN; Creatinine: Grade 3: 3.1 - 6\*ULN, Grade 4: \>6\*ULN; low phosphorous (hypophosphatemia): Grade 3: 1.0- 1.4 mg/dL, Grade 4: \<1.0mg/dL; high uric acid (hyperuricemia): Grade 3: 12.1 - 15.0 mg/dL, Grade 4: \>15.0 mg/dL.
Number of Participants With Confirmed Plasma HIV RNA < 400 c/mL at Week 48 (Defined by the Food and Drug Administration [FDA] Time to Loss of Virologic Response [TLOVR] Algorithm) Baseline (Day 1) and Week 48 TLOVR defines responders at Week 48 as participants with confirmed HIV RNA \<400 c/mL through Week 48 without intervening virologic rebound or treatment discontinuation. Virologic rebound is defined as confirmed on-treatment HIV RNA \<400 c/mL or last on-treatment HIV RNA \<400 c/mL followed by discontinuation. Participants are considered failures in this analysis if they experienced virologic rebound at or before Week 48, discontinued before Week 48, never responded by Week 48, never received study therapy or had missing HIV RNA at Week 48 and beyond.
Reduction of log10 HIV RNA Levels From Baseline to Week 48 Baseline (Day 1) and Week 48 Changes from baseline in log10 HIV RNA levels were calculated.
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48 Baseline (Day 1) and Week 48. Mean change from baseline in CD4 cell counts was determined.
Treatment Emergent Resistance in Isolates From Participants With Virologic Failure at Week 48 Baseline (Day 1) and Week 48 Participants with virologic failure are those who never suppressed (HIV RNA \<400 c/mL) and were on study through Week 48, or who rebounded to HIV RNA \>= 400 c/mL and those who discontinued due to insufficient viral load response. IAS=International AIDS Society, PI=protease inhibitor, RTI=reverse transcription inhibitor, TAMS=Thymidine Analogue-Associated Mutations, NRTI=non-nucleotide reverse transcriptase inhibitor, M184V= Methionine-to-valine mutation at position 184 (in reverse transcription \[RT\] gene), FC=fold change
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced AEs Leading to Discontinuation Through Week 48 From baseline (Day 1) to Week 48. AEs:new,untoward medical occurrences/worsening of pre-existing medical condition,drug-related or not.SAEs:any AE that:resulted in death;was life threatening;resulted in a persistent or significant disability/incapacity;resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was cancer;or overdose.Discontinuation from study was due either to an AE or was conducted at the investigator's discretion.AEs represented here include SAEs, which are not included in the AE count represented in the AE xml upload section. As such, these numbers may not match.
Mean Change in Weight From Baseline at Week 48 Baseline (Day 1) and Week 48 Mean change in body weight from baseline was determined.
Mean Change in Fasting Glucose at Week 48 Baseline (Day 1) and Week 48. Mean change from baseline in fasting glucose at Week 48.
Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 48 Baseline (Day 1) and Week 48 MOS-HIV is developed to assess a participant's health and functional status associated with HIV infection. The questionnaire is applied to participants with adequate linguistic skills and consists of 35 items. The questionnaire derives an overall health score and 10 subscale scores (health transitions, pain, physical functioning, role functioning, social functioning, cognitive functioning, mental health, energy/fatigue, health distress and quality of life).The subscale and summary scores range from 0-100 with a higher score indicating better health.
Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 12 (IBS-QoL) IBS-QoL is administered at baseline (Day 1) and Week 12. The IBS-QoL questionnaire has 34 items and an overall score and 8 subscale scores: dysphoria,interference with activity,body image,health worry, food avoidance,social reaction,sexual, and relationships. Overall and subscores transformed to a 0-100 scale (0=lowest score, 100=highest possible score). Scores between these values represent the percentage of the total possible score achieved. Higher scores=better IBS-related QoL. A 14-point change from BL in IBS-QoL score in women with moderate to severe functional bowel disorders is a minimally important difference based on pain and satisfaction.
Number of Participants Who Adhered to Regimen as Measured by Multicenter AIDS Cohort Study Adherence Questionnaire (MACS) at Week 48 Week 48 The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Adherence to regimen was defined as taking 100% of medicine (all doses and numbers of pills as prescribed for each medicine). This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Number of Participants With Laboratory Abnormalities in Hematology Through Week 48: Hemoglobin, Hematocrit, Platelet Count, International Normalized Ratio (INR), Neutrophils, Prothrombin Time (PT) and White Blood Cells (WBC) At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Hematology abnormalities were graded per modified World Health Organization (WHO) criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: Hemoglobin: Grade 3: 6.5-7.9 g/dL, Grade 4: \<6.5 g/dL; Hematocrit: Grade 3: \>=19.5 - 24%, Grade 4: \<19.5%; platelet count: Grade 3: 20,000- 49, 999/ mm\^3, Grade 4: \<20,000/mm\^3; INR: Grade 3 Absolute Neutrophil Count (ANC): Grade 3: \>= 500 - \<750/mm\^3, Grade 4: \<500/mm\^3; PT: Grade 3: 1.51 - 3.0\*ULN, Grade 4: \>3\*ULN; WBC: Grade 3: \>=800 to \<1000/mm\^3, Grade 4: \<80/mm\^3.
Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 24 Baseline (Day 1) and Week 24. Medical Outcomes Study HIV Health Survey (MOS-HIV) is developed to assess a patient's health and functional status associated with HIV infection. The MOS-HIV questionnaire is applied to participants with adequate linguistic skills. The subscale and summary scores range from 0-100 with a higher score indicating better health.
Number of Participants With Laboratory Abnormalities in Liver Function Test Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Liver function tests abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), while albumin was graded as per NCI-CTCAE. Grade 3 and 4 criteria were: ALT, AST, alkaline phosphatase: Grade 3: 5.1- 10\*ULN, Grade 4: \>10\*ULN; direct and total bilirubin: Grade 3: 2.6- 5\*ULN, Grade 4: \>5\*ULN, Albumin: Grade 3: \<2g/dL.
Number of Participants With Laboratory Abnormalities in Fasting Lipids Level Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Laboratory measurements marked as abnormal, as per NCEP-ATP-III guided categories. The following definitions specify the criteria for MAs in fasting lipids: Total cholesterol: Grade 3: 240 - 300 mg/dL, Grade 4: \>=240 mg/dL, triglycerides: Grade 3: 200 - \<500 mg/dL, Grade 4: \>=500 mg/dL.
Number of Participants With Laboratory Abnormalities in Fasting Glucose Levels Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in fasting glucose: hypoglycemia: Grade 3: 30-39 mg/dL, Grade 4: \<30 mg/dL; hyperglycemia: 251-500 mg/dL, Grade 4: \>500 mg/dL.
Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 48 DEXA scans were performed at baseline (within 30 days of starting study treatment), and at Weeks 48. The mean percent change from baseline in limb, trunk and total body fat was measured by DEXA. Limb fat: a physical sign of lipoatrophy, clinical improvement in limb fat is associated with a decrease in values. Trunk fat: a physical sign of lipohypertrophy, clinical improvement in trunk fat is associated with a decrease in values. Total body fat: association of many factors like trunk fat, limb fat, weight etc. Clinical improvement in total body fat cannot be predicted based solely an increase or decrease of these values.
Number of Participants With Laboratory Abnormalities in Electrolytes Through Week 48 At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Serum electrolytes abnormalities,graded per modified WHOcriteria.Ranges were:hypercarbia:Grade3:41-45milliequivalents(meq)/L,Grade4:\>45meq/L;hypocarbia:Grade3:10-14 meq/L,Grade4:\<10 meq/L;hypercalcemia:Grade3:12.6 - 13.5 mg/dL,Grade 4:\>13.5 mg/dL;hypocalcemia:6.1-6.9mg/dL,Grade4:\<6.1mg/dL;hyperchloremia:Grade 3: 121-125 meq/L,Grade4:\>125meq/L;hypochloremia:Grade 3:80-84 meq/L,Grade4:\<80meq/L;hyperkalemia:Grade3:6.6-7.0meq/L,Grade4:\>7.0meq/L;hypokalemia:Grade3:2.0-2.4 meq/L,Grade4:\<2.0meq/L;hypernatremia:Grade3:158-165 meq/L,Grade4:\>165meq/L;hyponatremia:Grade 3:116-122 meq/L,Grade 4:115 meq/L.
Number of Participants With Laboratory Abnormalities in Fasting Lipids Through Week 48 At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Laboratory measurements marked as abnormal, as per National Cholesterol Education Program (NCEP)- Adult Treatment Panel (ATP)-III guided categories. The following definitions specify the criteria for MAs in fasting lipids: Total cholesterol: Grade 3: 240 - 300 mg/dL, Grade 4: \>=240 mg/dL, triglycerides: Grade 3: 200 - \<500 mg/dL, Grade 4: \>=500 mg/dL.
Number of Participants With HIV RNA < 400 c/mL) at Week 96 Baseline (Day 1) and Week 96 HIV RNA \<400 c/mL is a less stringent measure of viral suppression (highest threshold of assay) and indicates that a participant has responded to treatment.
Mean Changes in Fasting Lipids at Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Mean change from baseline in fasting lipids at Week 96 was determined.
Number of Participants With Laboratory Abnormalities in Electrolytes Level Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Serum electrolytes abnormalities,graded per modified WHOcriteria.Ranges were:hypercarbia:Grade3:41-45milliequivalents(meq)/L,Grade4:\>45meq/L;hypocarbia:Grade3:10-14 meq/L,Grade4:\<10 meq/L;hypercalcemia:Grade3:12.6 - 13.5 mg/dL,Grade 4:\>13.5 mg/dL;hypocalcemia:6.1-6.9mg/dL,Grade4:\<6.1mg/dL;hyperchloremia:Grade 3: 121-125 meq/L,Grade4:\>125meq/L;hypochloremia:Grade 3:80-84 meq/L,Grade4:\<80meq/L;hyperkalemia:Grade3:6.6-7.0meq/L,Grade4:\>7.0meq/L;hypokalemia:Grade3:2.0-2.4 meq/L,Grade4:\<2.0meq/L;hypernatremia:Grade3:158-165 meq/L,Grade4:\>165meq/L;hyponatremia:Grade 3:116-122 meq/L,Grade 4:115 meq/L.
Mean Change From Baseline in Body Weight at Week 96 Baseline (Day 1) and Week 96 Mean change from baseline in weight at Week 96
Percentage of Participants With Lipoatrophy at Week 96 Baseline (Day 1) and Week 96 Lipoatrophy, redistribution of body fat was defined as \>= 20% decrease in limb fat. The percentage of participants with lipoatrophy from baseline was determined.
Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 48 At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in urinalysis: Proteinuria: Grade 3: 4= or \>2-3.5 g loss/day, Grade 4: \>3.5 g loss/day.
Number of Participants With Laboratory Abnormalities in Fasting Glucose Through Week 48 At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48. Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in fasting glucose: hypoglycemia: Grade 3: 30-39 mg/dL, Grade 4: \<30 mg/dL; hyperglycemia: 251-500 mg/dL, Grade 4: \>500 mg/dL.
Mean Change in Body Mass Index (BMI) in Participants at Week 48 Baseline (Day 1) and Week 48 Mean change in BMI from baseline at Week 48 was determined.
Mean Change From Baseline (BL) in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 4 (IBS-QoL) IBS-QoL is administered at baseline (Day 1) and Week 4. The IBS-QoL questionnaire has 34 items and an overall score and 8 subscale scores: dysphoria,interference with activity,body image,health worry, food avoidance,social reaction,sexual, and relationships. Overall and subscores transformed to a 0-100 scale (0=lowest score, 100=highest possible score). Scores between these values represent the percentage of the total possible score achieved. Higher scores=better IBS-related QoL. A 14-point change from BL in IBS-QoL score in women with moderate to severe functional bowel disorders is a minimally important difference based on pain and satisfaction.
Number of Participants With HIV RNA < 50 c/mL) at Week 96 Baseline (Day 1) and Week 96 HIV RNA \< 50 c/mL is the most stringent measure of viral suppression (lowest threshold of assay) and indicates that a participant has responded to treatment.
Mean Change From Baseline in CD4 Cell Count at Week 96 Baseline (Day 1) and Week 96 Mean change from baseline in CD4 count among treated participants was determined.
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation Through Week 96 From Day 1 through Week 96 AEs:new,untoward medical occurrences/worsening of pre-existing medical condition,drug-related or not.SAEs:any AE that:resulted in death;was life threatening;resulted in a persistent or significant disability/incapacity;resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was cancer;or overdose.Discontinuation from study was due either to an AE or was conducted at the investigator's discretion.AEs represented here include SAEs, which are not included in the AE count represented in the AE xml upload section. As such, these numbers may not match.
Mean Changes in Fasting Insulin at Week 96 Baseline (Day 1) and Week 96. Mean change from baseline in fasting insulin at Week 96.
Number of Participants With Laboratory Abnormalities in Renal Function Test Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Renal function test abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: BUN: Grade 3: 5.1- 10\*ULN, Grade 4: \>10\*ULN; Creatinine: Grade 3: 3.1 - 6\*ULN, Grade 4: \>6\*ULN; low phosphorous (hypophosphatemia): Grade 3: 1.0- 1.4 mg/dL, Grade 4: \<1.0mg/dL; high uric acid (hyperuricemia): Grade 3: 12.1 - 15.0 mg/dL, Grade 4: \>15.0 mg/dL.
Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in urinalysis: Proteinuria: Grade 3: 4= or \>2-3.5 g loss/day, Grade 4: \>3.5 g loss/day.
Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 96 Baseline (Day 1) and Week 96. The mean percent change from baseline in limb, trunk and total body fat was measured by DEXA. Limb fat: a physical sign of lipoatrophy, clinical improvement in limb fat is associated with a decrease in values. Trunk fat: physical sign of lipohypertrophy, clinical improvement in trunk fat is associated with a decrease in values. Total body fat: association of many factors like trunk fat, limb fat, weight etc. Clinical improvement in total body fat cannot be predicted based solely an increase or decrease of these values.
Mean Percent Changes From Baseline in BMD Measured by DEXA at Week 96 Baseline (Day 1) and Week 96 Mean percent change from baseline in BMD of arms, legs, trunk and total body was measured using DEXA, an X-ray scan technique.
Mean Change in Fasting Insulin at Week 48 Baseline (Day 1) and Week 48. Mean change from baseline in fasting insulin at Week 48.
Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 24 Using the Irritable Bowel Syndrome Quality of Life (IBS-QoL) Baseline (Day 1) and Week 24 The IBS-QoL questionnaire has 34 items and an overall score and 8 subscale scores: dysphoria,interference with activity,body image,health worry, food avoidance,social reaction,sexual, and relationships. Overall and subscores transformed to a 0-100 scale (0=lowest score, 100=highest possible score). Scores between these values represent the percentage of the total possible score achieved. Higher scores=better IBS-related QoL. A 14-point change from BL in IBS-QoL score in women with moderate to severe functional bowel disorders is a minimally important difference based on pain and satisfaction.
Number of Participants With Laboratory Abnormalities in Hematology: Hemoglobin, Hematocrit, Platelet Count, INR, Neutrophils, PT and WBC Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Hematology abnormalities were graded per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: Hemoglobin: Grade 3: 6.5-7.9 g/dL, Grade 4: \<6.5 g/dL; Hematocrit: Grade 3: \>=19.5 - 24%, Grade 4: \<19.5%; platelet count: Grade 3: 20,000- 49, 999/ mm\^3, Grade 4: \<20,000/mm\^3; INR: Grade 3 Absolute Neutrophil Count (ANC): Grade 3: \>= 500 - \<750/mm\^3, Grade 4: \<500/mm\^3; PT: Grade 3: 1.51 - 3.0\*ULN, Grade 4: \>3\*ULN; WBC: Grade 3: \>=800 to \<1000/mm\^3, Grade 4: \<80/mm\^3.
Mean Change From Baseline in Trunk-to-limb Fat Ratio Measured by DEXA at Week 48 DEXA scans were taken at Baseline (Day 1) and at Weeks 48. Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement was associated with a decrease in values.
Median Changes From Baseline at Week 96 in VAT-to-TAT, VAT-to-SAT and, Trunk-to-limb Fat Ratio Measured by Computed Tomography (CT)/DEXA Baseline (Day 1) and Week 96. Mean Change From Baseline in BMI at Week 96 Baseline (Day 1) and Week 96 Mean change From baseline in BMI at Week 96 was determined.
Mean Change From Baseline in Waist Circumference at Week 48 Baseline (Day 1) and Week 48 Mean change from baseline in waist circumference at Week 48 was determined.
Mean Change From Baseline in BMI at Week 48 Baseline (Day 1) and Week 48. Mean change from baseline in BMI at Week 48 was determined.
Mean Changes in Fasting Glucose at Week 96 Baseline (Day 1) and Week 96 Mean change from baseline in fasting glucose at Week 96 was determined.
Reduction of log10 HIV RNA Levels From Baseline at Week 96 Baseline (Day 1) and Week 96 Changes from baseline in log10 HIV RNA levels were calculated.
Number of Participants With Laboratory Abnormalities in Serum Enzyme Levels Through Week 96 At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96. Laboratory measurements marked as abnormal, as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria in serum enzymes were: CPK: Grade 3: 5.1 - 10.0 \* ULN, Grade 4: \>10\* ULN; Lipase: Grade 3: 2.10 - 5.0\* ULN, Grade 4: 5.0\* ULN.
Number of Participants With Virologic Failure Showing Treatment Emergent Resistance Through Week 96 Baseline (Day 1) and Week 96. Virologic failure participants defined as participants who were never suppressed (HIV RNA \< 400 c/mL) and on study through Week 48, or who rebounded to HIV RNA ≥ 400 c/mL, and those who discontinued due to insufficient viral load response using CVR (NC=F). IAS-USA=International AIDS Society-United States of America, PI=protease inhibitor, RTI=reverse transcription inhibitor, TAMS=Thymidine Analogue-Associated Mutations, NRTI=non-nucleotide reverse transcriptase inhibitor, M184/V= Methionine-to-valine mutation at position 184 (in reverse transcription \[RT\] gene), FC=fold change
Mean Percent Changes From Baseline in Bone Mineral Density (BMD) Measured by DEXA at Week 48 DEXA scans were taken at Baseline (Day 1) and Week 48. Mean percent change from baseline in BMD of arms, legs, trunk and total body was measured using DEXA, an X-ray scan technique.
Mean Change From Baseline in Body Weight at Week 48 Baseline (Day 1) and Week 48 Mean change from baseline in body weight at Week 48 was determined.
Mean Change From Baseline in Waist-to-hip-ratio at Week 96 Baseline (Day 1) and Week 96 Mean change from baseline in waist-to-hip-ratio at Week 96 was determined.
Mean Change From Baseline in Waist-to-hip-ratio at Week 48 Baseline (Day 1) and Week 48 Mean change from baseline in waist-to-hip-ratio at Week 48 was determined.
Mean Changes From Baseline in Body Weight at Week 96 Physical examination was performed at Baseline (Day 1) and Weeks 48 and 96. Mean change in body weight from baseline was determined.
Mean Change From Baseline in Waist Circumference at Week 96 Baseline (Day 1) and Week 96. Mean change From baseline in waist circumference at Week 96 was determined.
Trial Locations
- Locations (1)
Local Institution
🇬🇧Manchester, Greater Manchester, United Kingdom