Phase 1
Completed N=16
A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.
Source: ClinicalTrials.gov NCT00435929 ↗Enrolled (actual)
16
Serious AEs
6.3%
Results posted
Jan 2016
Primary outcomePrimary: Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours After Dosing (AUC 0-12h) of Saquinavir (SQV) and Ritonavir (RTV) — 28518; 24332; 10985; 9930 ng*hr/mL
Summary
This 2 arm study will assess the effect of moderate liver impairment on the pharmacokinetics of saquinavir and ritonavir at steady state following administration of saquinavir/ritonavir 1000mg/100mg po bid in HIV patients. Saquinavir/ritonavir will be administered concomitantly with 2 to 3 active nucleoside reverse transcriptase inhibitors. The study will compare a group of HIV patients without known liver disease and a group with moderate liver disease. The anticipated time on study treatment is <3 months, and the target sample size is <100 individuals.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours After Dosing (AUC 0-12h) of Saquinavir (SQV) and Ritonavir (RTV) |
28518; 24332; 10985; 9930 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of SQV and RTV |
4300; 3610; 1500; 1460 | — |
| SECONDARY Time of Maximum Plasma Concentration (Tmax) of SQV and RTV |
5.00; 5.00; 4.29; 4.07 | — |
| SECONDARY Terminal Half-life (T1/2) of SQV and RTV |
3.31; 4.10; 3.80; 4.82 | — |
| SECONDARY Minimum Observed Plasma Concentration (Cmin) of SQV and RTV |
965; 834; 399; 418 | — |
| SECONDARY Plasma Clearance After Oral Administration (CL/F) of SQV and RTV |
47.052; 84.416; 9.289; 12.568 | — |
| SECONDARY Volume of Distribution (Vd) of SQV and RTV |
213.294; 464.049; 50.232; 102.585 | — |
| SECONDARY Cluster of Differentiation 4 (CD4 ) Count |
540.000; 451.444; 638.500; 558.000; 683.571; 566.333 | — |
| SECONDARY Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Number Participants With Abnormal Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
1; 0; 0; 0; 0; 1 | — |
Eligibility Criteria
Inclusion Criteria
- adult patients, 18-65 years of age;
- HIV infection;
- normal liver function, or moderate liver disease (Child-Pugh grade B);
- antiretroviral therapy naive and eligible to take antiretroviral treatment as per treatment guidelines, or treatment experienced for at least 4 weeks prior to first dosing.
Exclusion Criteria
- severe ascites at screening, or Child-Pugh grade C;
- acute infection or current malignancy requiring treatment;
- taking any inhibitor of CYP3A4 (with the exception of anti-HIV drugs) within 14 days prior to first dosing;
- taking any inducer of CYP3A4 (with the exception of anti-HIV drugs) within 4 weeks prior to pharmacokinetic evaluation (day 14 or 28);
- evidence of resistance to saquinavir.
Data sourced from ClinicalTrials.gov (NCT00435929). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.