HIV InfectionsPhase 1NCT00435929

A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.

A Phase 1 study testing Ritonavir and saquinavir [Invirase] in people with HIV Infections, run by Hoffmann-La Roche at 8 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: HIV Infections
What is being tested?: Ritonavir and saquinavir [Invirase]
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 8 sitesin 3 countries
Study dates: Sep 2006to Nov 2009
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

8 sites in 3 countries.

Country

City, postcode or hospital

8 sites in 3 countries

United States5 sites

Study site
Chicago, Illinois, 60612
Study site
Dallas, Texas, 75204
Study site
Philadelphia, Pennsylvania, 19104
Study site
Somers Point, New Jersey, 08244
Study site
Voorhees Township, New Jersey, 08043

Other trials in United States

Canada2 sites

Study site
Ottawa, Ontario, K1H 8L6
Study site
Toronto, Ontario, M5G 2C4

Other trials in Canada

Puerto Rico1 site

Study site
San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: Effect of Moderate Liver Impairment on the Pharmacokinetics of Saquinavir After Administration of Saquinavir/Ritonavir 1000/100mg BID in HIV Patients

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.

Conditions: HIV Infections
Being tested: Ritonavir, saquinavir [Invirase]
Keywords: Treatment Naive
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RitonavirDrug
100mg po bid
saquinavir [Invirase]Drug
1000mg po bid

Study groups in NCT00435929
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: Ritonavir; Drug: saquinavir [Invirase]
2	Experimental	Not described Receives: Drug: Ritonavir; Drug: saquinavir [Invirase]

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Maximum Observed Plasma Concentration (Cmax) of SQV and RTV
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14

Secondary outcomes (9)

Time of Maximum Plasma Concentration (Tmax) of SQV and RTV
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Terminal Half-life (T1/2) of SQV and RTV
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Minimum Observed Plasma Concentration (Cmin) of SQV and RTV
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
Plasma Clearance After Oral Administration (CL/F) of SQV and RTV
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
Volume of Distribution (Vd) of SQV and RTV
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.
Measured: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
Cluster of Differentiation 4 (CD4 ) Count
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.
Measured: Screening (Day -35 to -1), pre-dose on Day 8, Day 14 and at follow up (Day 28-Day 35)
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
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.
Measured: Up to Day 35
Number Participants With Abnormal Vital Signs
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.
Measured: Up to Day 35
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
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.
Measured: Up to Day 35

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2006Nov 2009

First posted16 Feb 2007 (estimated)
Study startSep 2006
Primary completionNov 2009
Study completionNov 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00435929
Sponsor's protocol ID: BP17921
Status last verified: Feb 2018
First submitted: 15 Feb 2007
Last updated: 29 Mar 2018
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Moderate Liver Impairment on the Pharmacokinetics of Saquinavir After Administration of Saquinavir/Ritonavir 1000/100mg BID in HIV Patients
ClinicalTrials.gov ID: NCT00435929
Acronym / sponsor ID: BP17921
Conditions: HIV Infections
Keywords: Treatment Naive
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: Sep 2006
Primary completion: Nov 2009 (actual)
Study completion: Nov 2009 (actual)
First posted: 16 Feb 2007 (estimated)
Results: Posted 8 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: Ritonavir, Drug: saquinavir [Invirase]
2	Experimental	Drug: Ritonavir, Drug: saquinavir [Invirase]

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ritonavir100mg po bid	Drug	1, 2
saquinavir [Invirase]1000mg po bid	Drug	1, 2

Primary outcome

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)
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose 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.
Maximum Observed Plasma Concentration (Cmax) of SQV and RTV
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose 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.

9 secondary outcomes

Time of Maximum Plasma Concentration (Tmax) of SQV and RTV
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Terminal Half-life (T1/2) of SQV and RTV
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Minimum Observed Plasma Concentration (Cmin) of SQV and RTV
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
Plasma Clearance After Oral Administration (CL/F) of SQV and RTV
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
Volume of Distribution (Vd) of SQV and RTV
Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14
Cluster of Differentiation 4 (CD4 ) Count
Time frame: Screening (Day -35 to -1), pre-dose on Day 8, Day 14 and at follow up (Day 28-Day 35)
Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters
Time frame: Up to Day 35
Number Participants With Abnormal Vital Signs
Time frame: Up to Day 35
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to Day 35

Results and safety

Results posted to the registry on 8 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Liver Function	7	7
Moderate Hepatic Impairment	9	9

Primary outcome: 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)

Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14. Mean (Standard Deviation). Unit: ng*hr/mL

Measure	Normal Liver Function n = 7	Moderate Hepatic Impairment n = 7
AUC for SQV	28518 (20157)	24332 (24700)
AUC for RTV	10985 (1723)	9930 (5243)

Normal Liver Function vs Moderate Hepatic Impairment: Geometric mean ratio: 0.656 (90% CI 0.268 to 1.603)
Normal Liver Function vs Moderate Hepatic Impairment: Geometric mean ratio: 0.764 (90% CI 0.505 to 1.156)

Population analysed: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of SQV and RTV

Time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14. Mean (Standard Deviation). Unit: ng/mL

Measure	Normal Liver Function n = 7	Moderate Hepatic Impairment n = 7
Cmax of SQV	4300 (2940)	3610 (3000)
Cmax of RTV	1500 (294)	1460 (690)

Normal Liver Function vs Moderate Hepatic Impairment: Geometric Mean Ratio: 0.716 (90% CI 0.311 to 1.644)
Normal Liver Function vs Moderate Hepatic Impairment: Geometric mean ratio: 0.844 (90% CI 0.551 to 1.292)

Population analysed: Pharmacokinetic (PK) analysis population: All participants who adhered to the study protocol and had evaluable concentration data and PK parameters on Day 14.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 35. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Liver Function	0 of 7 (0%)	3 of 7 (42.9%)	Not reported
Moderate Hepatic Impairment	1 of 9 (11.1%)	5 of 9 (55.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

8 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ritonavir and saquinavir [Invirase] in people with HIV Infections, run by Hoffmann-La Roche at 8 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00435929.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2018.