Trial Outcomes & Findings for A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection. (NCT NCT00435929)
NCT ID: NCT00435929
Last Updated: 2018-03-29
Results Overview
Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the area under the plasma concentration-time curve from 0 to 12 hours after dosing (AUC (0-12h) of SQV and RTV The AUC (0-12hours) was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Results posted on
2018-03-29
Participant Flow
The study was conducted from 12 September 2006 to 09 April 2009 at 3 sites in US and 2 in Canada.
Total 19 participants were screened. A total 9 participants with HIV infection with moderate liver disease (Group 2) and 7 participants with HIV infection with normal liver function (Group 1) were enrolled in the study. Participants in Group 1 were matched with those in Group 2 on the basis of age, gender, weight, and tobacco use.
Participant milestones
| Measure |
Normal Liver Function
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
9
|
|
Overall Study
COMPLETED
|
7
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.
Baseline characteristics by cohort
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=9 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the area under the plasma concentration-time curve from 0 to 12 hours after dosing (AUC (0-12h) of SQV and RTV The AUC (0-12hours) was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
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)
AUC for RTV
|
10985 ng*hr/mL
Standard Deviation 1723
|
9930 ng*hr/mL
Standard Deviation 5243
|
|
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)
AUC for SQV
|
28518 ng*hr/mL
Standard Deviation 20157
|
24332 ng*hr/mL
Standard Deviation 24700
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
The plasma concentration (Cmax) is defined as maximum observed analyte concentration. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the maximum observed plasma concentration (C max) of SQV and Ritonavir RTV The Cmax was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of SQV and RTV
Cmax of SQV
|
4300 ng/mL
Standard Deviation 2940
|
3610 ng/mL
Standard Deviation 3000
|
|
Maximum Observed Plasma Concentration (Cmax) of SQV and RTV
Cmax of RTV
|
1500 ng/mL
Standard Deviation 294
|
1460 ng/mL
Standard Deviation 690
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the time of maximum plasma concentration of SQV and RTV. The Tmax was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of SQV and RTV
Tmax of SQV
|
5.00 hour
Standard Deviation 1.83
|
5.00 hour
Standard Deviation 2.38
|
|
Time of Maximum Plasma Concentration (Tmax) of SQV and RTV
Tmax of RTV
|
4.29 hour
Standard Deviation 1.50
|
4.07 hour
Standard Deviation 1.75
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
Terminal half-life is the time measured for the plasma concentration to decrease by one half. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the terminal half-life (T1/2) of SQV and RTV. The T1/2 was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Terminal Half-life (T1/2) of SQV and RTV
T1/2 of SQV
|
3.31 hour
Standard Deviation 0.823
|
4.10 hour
Standard Deviation 1.90
|
|
Terminal Half-life (T1/2) of SQV and RTV
T1/2 of RTV
|
3.80 hour
Standard Deviation 0.908
|
4.82 hour
Standard Deviation 2.82
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
Cmin is the minimum blood plasma concentration that a drug achieves. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the minimum observed plasma concentration (C min) of SQV and RTV The Cmin was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Minimum Observed Plasma Concentration (Cmin) of SQV and RTV
Cmin of SQV
|
965 ng/mL
Standard Deviation 920
|
834 ng/mL
Standard Deviation 870
|
|
Minimum Observed Plasma Concentration (Cmin) of SQV and RTV
Cmin of RTV
|
399 ng/mL
Standard Deviation 172
|
418 ng/mL
Standard Deviation 300
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
The CL/F is the oral clearance; that is clearance based on oral bioavailability. The Pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the plasma clearance after oral administration (CL/F)of SQV and RTV The CL/F was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Plasma Clearance After Oral Administration (CL/F) of SQV and RTV
CL/F of SQV
|
47.052 L/hr
Standard Deviation 20.254
|
84.416 L/hr
Standard Deviation 68.645
|
|
Plasma Clearance After Oral Administration (CL/F) of SQV and RTV
CL/F of RTV
|
9.289 L/hr
Standard Deviation 1.392
|
12.568 L/hr
Standard Deviation 5.885
|
SECONDARY outcome
Timeframe: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14Population: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.
Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the Vd of SQV and RTV The Vd was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Volume of Distribution (Vd) of SQV and RTV
Vd of SQV
|
213.294 Litres
Standard Deviation 95.048
|
464.049 Litres
Standard Deviation 334.460
|
|
Volume of Distribution (Vd) of SQV and RTV
Vd of RTV
|
50.232 Litres
Standard Deviation 11.888
|
102.585 Litres
Standard Deviation 112.579
|
SECONDARY outcome
Timeframe: Screening (Day -35 to -1), pre-dose on Day 8, Day 14 and at follow up (Day 28-Day 35)Population: PD analysis population: All participants who received at least 1 dose of the study medication and had at least 1 pharmacodynamic (PD) measure were included in the PD analysis population.
The pharmacodynamic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the cluster of differentiation 4 (CD4) count in participants in each group.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=7 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Cluster of Differentiation 4 (CD4 ) Count
Screening; n=7, 9
|
540.000 cells/cubic millimeter
Standard Deviation 218.187
|
451.444 cells/cubic millimeter
Standard Deviation 249.011
|
|
Cluster of Differentiation 4 (CD4 ) Count
Day 8;n=6, 9
|
638.500 cells/cubic millimeter
Standard Deviation 254.358
|
558.000 cells/cubic millimeter
Standard Deviation 243.994
|
|
Cluster of Differentiation 4 (CD4 ) Count
Day 14;n=7, 9
|
683.571 cells/cubic millimeter
Standard Deviation 250.160
|
566.333 cells/cubic millimeter
Standard Deviation 257.484
|
|
Cluster of Differentiation 4 (CD4 ) Count
Follow up; n=6, 8
|
692.500 cells/cubic millimeter
Standard Deviation 150.045
|
567.625 cells/cubic millimeter
Standard Deviation 261.947
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Safety population: All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety analysis.
Laboratory parameters specified in Clinical Operating Guidelines (COG) were summarized. AIDS Clinical Trial Group (ACTG) and American Heart Association (AHA) criteria were used to grade COG laboratory test values. Laboratory parameters for which an increase to Grade 3 (G3) or Grade 4 (G4) occurred are presented in the table below.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=9 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
ASAT (SGOT), (Hyper) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
ASAT (SGOT), (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Alkaline Phosphatase, (Hyper) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Alkaline Phosphatase, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
ALAT (SGPT), (Hyper) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
ALAT (SGPT), (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Direct Bilirubin, (Hyper) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Direct Bilirubin, (Hyper) G4
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Creatinine, (Hyper) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Creatinine, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Albumin, (Hypo) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Albumin, (Hypo) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Prothrombin Time seconds(Hyper) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Prothrombin Time seconds (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Creatine Kinase, (Hyper) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Creatine Kinase, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Cholesterol, (Hyper) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Cholesterol, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Triglycerides, (Hyper) G3
|
2 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Triglycerides, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Calcium, (Hypo) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Calcium, (Hypo) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Potassium, (Hypo) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Potassium, (Hypo) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Sodium, (Hypo) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Sodium, (Hypo) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Platelets, (Hypo) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Platelets, (Hypo) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Neutrophils, (Hypo) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Neutrophils, (Hypo) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Fasting Glucose, (Hyper) G3
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Fasting Glucose, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Amylase, (Hyper) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Amylase, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Uric Acid, (Hyper) G3
|
0 participants
|
2 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Uric Acid, (Hyper) G4
|
0 participants
|
0 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Proteinuria 0 to 4+, (Hyper) G3
|
0 participants
|
1 participants
|
|
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Proteinuria 0 to 4+, (Hyper) G4
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Safety population: All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety analysis.
Abnormal Vital signs included are high and low Pulse rate (PR), high and how Temperature (Temp), high and low Systolic Blood Pressure (SBP) and high and low Diastolic Blood Pressure (DBP). Vital signs (SBP, DBP, PR,Temp) were measured after participants were in a semi-supine position for at least 5 minutes.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=9 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Number Participants With Abnormal Vital Signs
High-DBP
|
0 participants
|
0 participants
|
|
Number Participants With Abnormal Vital Signs
High PR
|
0 participants
|
0 participants
|
|
Number Participants With Abnormal Vital Signs
Low PR
|
0 participants
|
0 participants
|
|
Number Participants With Abnormal Vital Signs
High Temp
|
0 participants
|
0 participants
|
|
Number Participants With Abnormal Vital Signs
Low Temp
|
0 participants
|
0 participants
|
|
Number Participants With Abnormal Vital Signs
High-SBP
|
1 participants
|
1 participants
|
|
Number Participants With Abnormal Vital Signs
Low-SBP
|
0 participants
|
0 participants
|
|
Number Participants With Abnormal Vital Signs
Low-DBP
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Up to Day 35Population: Safety population: All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety analysis.
Abnormal ECG findings included are high and low Heart Rate (HRT), high and low PQ/PR interval (PQ/PR), high and low QRS interval (QRS), high and low QT interval (QT), high and low QTCB interval (QTcB), high and low QTcF interval (QTcF), high and low RR interval (RR), high and low T Wave, high and low U Wave, high and low ECG. The 12 Lead ECG was recorded after participants were in a semi-supine position for at least 5 minutes. Only participants with abnormal ECG findings are presented in the table below.
Outcome measures
| Measure |
Normal Liver Function
n=7 Participants
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=9 Participants
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- HRT ECG ; n=7, 9
|
1 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- HRT ECG; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- PQ (PR); n=7, 9
|
0 participants
|
1 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- PQ (PR); n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- QRS; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- QRS; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- QT; n=7, 9
|
0 participants
|
2 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- QT; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- QTcB; n=5, 8
|
0 participants
|
2 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- QTcB; n=5, 8
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- QTcF; n=5, 8
|
0 participants
|
2 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- QTcF; n=5, 8
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- RR; n=5, 8
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- RR; n=5, 8
|
1 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- T WAVE; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- T WAVE; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- U WAVE; n=1, 0
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- U WAVE; n=1, 0
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
HIGH- ECG; n=7, 9
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
LOW- ECG; n=7, 9
|
0 participants
|
0 participants
|
Adverse Events
Normal Liver Function
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Moderate Hepatic Impairment
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Normal Liver Function
n=7 participants at risk
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=9 participants at risk
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
Other adverse events
| Measure |
Normal Liver Function
n=7 participants at risk
Participants with human immunodeficiency virus (HIV) infection and with normal liver function receiving saquinavir (SQV)/ritonavir (RTV) 1000/100 mg orally twice a day (BID) for 14 days.
|
Moderate Hepatic Impairment
n=9 participants at risk
Participants with HIV infection and with moderate hepatic impairment receiving SQV/RTV 1000/100 mg orally BID for 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
42.9%
3/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Gastrointestinal disorders
Nausea
|
14.3%
1/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
33.3%
3/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
22.2%
2/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
General disorders
Fatigue
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
33.3%
3/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
General disorders
Oedema Peripheral
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
General disorders
Pain
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Infections and infestations
Influenza
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
1/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
0.00%
0/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Hepatobiliary disorders
Liver Tenderness
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
11.1%
1/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
|
Renal and urinary disorders
Micturition Urgency
|
14.3%
1/7 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
0.00%
0/9 • Up to Day 35
All participants who received at least 1 dose of study medication (whether or not they were withdrawn prematurely) and had safety follow-up data were included in safety population. .All AE's and SAE's were collected following the first dose, as well as those that started prior to dosing and worsened on or after the first dose.
|
Additional Information
F. Hoffmann-La Roche AG
Roche Trial Information Hotline
Phone: +41 61 6878333
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER