Human Immunodeficiency VirusPhase 1LIVERALNCT01289951

Pharmacokinetic Study of Raltegravir in Human Immunodeficiency Virus/Hepatitis C Virus (HIV/VHC) Coinfected Patients With Advanced (Child-Pugh C) Hepatic Cirrhosis

A Phase 1 study testing Raltegravir 400 mg/12hours in people with Human Immunodeficiency Virus and Hepatitis C, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.

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 years and older
Conditions the study is for: Human Immunodeficiency Virus, Hepatitis C
What is being tested?: Raltegravir 400 mg/12hours
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteSpain
Study dates: Dec 2010to Oct 2011
Phase: Phase 1
Are there results?: None posted in the registry

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults, clinically stable HIV/HCV coinfected patients on HAART with controlled viremia (<50 copies/ml) for at least 6 months. HAART will be based on a boosted protease inhibitor (lopinavir, fosamprenavir or darunavir). Hepatic Stability is defined by the absence of new events of descompensation (Child-Pugh score) in the previous six weeks with no data of progressive hepatic insufficiency.
Liver biopsy performed during the previous year showing no liver damage (F0-F1 in the Metavir score) or by elastometry results ≤ 6 Kpa, to classify patients in group B.
Liver cirrhosis guided by biopsy (F4 in the Metavir score) or elastometry: results ≥ 14 Kpa, to classify patients in group A.
Body mass index (BMI) in the range of 19-35 kg/m2.

Who cannot join

HBV surface antigen positive.
Clinical demonstration of a new descompensation event in the previous 6 weeks.
Alcohol abuse as an average daily consumption > 20g.
Treatment with boosted atazanavir, saquinavir or indinavir.
Concomitant treatment with phenytoin, phenobarbital and rifampinor other UGT1A1 inhibitors.
Use of any investigational agents (other than ART on expanded access) within 90 days of randomization.

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Active or previous HCV treatment with Ribavirin and /or Peg-interferon if sustained virological response achieved.
Women taking oral contraceptives
Pregnancy and lactancy.

Trial locations and contacts

1 site in 1 country.

Spain1 site

Hospital Universitario Ramón y Cajal.
Madrid, Madrid, 28034

Other trials in Spain

About this study

Official title: Phase I, Open Label, Unicentric Study of Multiple-dose Pharmacokinetics of Raltegravir in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus With and Without Advanced (Child-Pugh C) Hepatic Cirrhosis.

Raltegravir is the first integrase inhibitor used in humans. It has been shown to be highly efficacious and well tolerated in phase III clinical trials in multidrug experienced human immunodeficiency virus(HIV)-infected patients, as well as initial therapy in untreated patients. Pharmacokinetic studies in healthy adult subjects indicate that the major mechanism of clearance of the drug is glucuronidation mediated by UGT1A1, with a minor contribution of renal excretion of unchanged parent compound. Unlike CYP-based metabolism, glucuronidation is generally found to be relatively unaffected by hepatic disease. A single dose pharmacokinetic study of raltegravir in patients with mild to moderate hepatic insufficiency (Steigbigel et al. 2008) found no clinically important effect on the drug pharmacokinetic profile, with no dosage adjustment being necessary. The liver safety and tolerability of boosted atazanavir (ATV/r) has been evaluated in human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfected patients with advanced liver disease (decompensated cirrhosis) (Hermida JM et al. 4th IAS: Sidney, 2007). Similar to Raltegravir, ATV is also mainly metabolized by conjugation through UGT1A1. There is an urgent need for potent and efficacious ARV drugs with a clean safety liver profile even in patients with severe liver disease. The investigators hypothesized that pharmacokinetics will not be altered in HIV/HCV patients with advanced (Child-Pugh grade C) cirrhosis or in those with no histologic liver damage.

Conditions: Human Immunodeficiency Virus, Hepatitis C
Being tested: Raltegravir 400 mg/12hours
Keywords: HIV, VHC, Advanced hepatic cirrhosis, Pharmacokinetic, Raltegravir
Medical subject headings: Acquired Immunodeficiency Syndrome, Hepatitis C

What participants receive

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

Raltegravir 400 mg/12hoursDrug
Raltegravir 400 mg/12hoursDrug

Study groups in NCT01289951
Study group	Role	What they receive
Patients with Child-Pugh C hepatic-cirrhosis.	Experimental	VIH/VHC coinfected patients with advanced (Child-Pugh C) hepatic cirrhosis. Receives: Drug: Raltegravir 400 mg/12hours
VIH/VHC coinfected patients without liver damage.	Active comparator	Not described Receives: Drug: Raltegravir 400 mg/12hours

What is being measured

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

The area under the curve (AUC0-12) calculated from plasma concentrations, the maximum concentration (Cmax) and the the minimum concentration (Cmin) of Raltegravir 400 mg/12 hours in the steady state for both arms.
On the fifth day of treatment, patient will be hospitalized in the clinical trial unit in order to obtaine plasma concentrations previous to the administration of the corresponding dose (basal) and at the following times post-administration: 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, and 12h. With these measures, (AUC0-12), Cmax and Cmin will be calculated in order to describe the pharmacokinetic of Raltegravir 400 mgBID in the steady state in both arms
Measured: On the fifth day of treatment with raltegravir

Secondary outcomes (1)

Change from baseline in hematology and biochemistry parameters at day 5 and 15, number of adverse events (serious and non serious) notified and number of patients who discontinue the study (drop-out rate).
Hematology and biochemistry parameters, adverse events notified during the study and drop-out rate will be recorded in order to evaluate the safety and tolerability of multiple doses of raltegravir in HIV/HCV coinfected patients, with no liver damage and with advanced cirrhosis.
Measured: On day 1, 5 and 15

Timeline

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

Dec 2010Oct 2011

First posted4 Feb 2011 (estimated)
Study startDec 2010
Primary completionJun 2011
Study completionOct 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
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: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01289951
Sponsor's protocol ID: LIVERAL
Acronym: LIVERAL
Status last verified: Jan 2013
First submitted: 1 Feb 2011
Last updated: 1 Feb 2013
Results posted: No
Data monitoring committee: No

Publications

Hernandez-Novoa B, Moreno A, Perez-Elias MJ, Quereda C, Dronda F, Casado JL, Madrid-Elena N, Aguilar M, Fumero E, Molto J, Moreno S. Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). J Antimicrob Chemother. 2014 Feb;69(2):471-5. doi: 10.1093/jac/dkt386. Epub 2013 Oct 4.
PubMed 24097843

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?

See locations

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All Human Immunodeficiency Virus trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I, Open Label, Unicentric Study of Multiple-dose Pharmacokinetics of Raltegravir in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus With and Without Advanced (Child-Pugh C) Hepatic Cirrhosis.
ClinicalTrials.gov ID: NCT01289951
Acronym / sponsor ID: LIVERAL / LIVERAL
Conditions: Human Immunodeficiency Virus, Hepatitis C
Keywords: HIV, VHC, Advanced hepatic cirrhosis, Pharmacokinetic, Raltegravir
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: Dec 2010
Primary completion: Jun 2011 (actual)
Study completion: Oct 2011 (actual)
First posted: 4 Feb 2011 (estimated)
Results: Not posted in the source record

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
Patients with Child-Pugh C hepatic-cirrhosis.	Experimental	Drug: Raltegravir 400 mg/12hoursVIH/VHC coinfected patients with advanced (Child-Pugh C) hepatic cirrhosis.
VIH/VHC coinfected patients without liver damage.	Active comparator	Drug: Raltegravir 400 mg/12hours

Who may qualify

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

Key inclusion criteria (4 listed)

Adults, clinically stable HIV/HCV coinfected patients on HAART with controlled viremia (<50 copies/ml) for at least 6 months. HAART will be based on a boosted protease inhibitor (lopinavir, fosamprenavir or darunavir). Hepatic Stability is defined by the absence of new events of descompensation (Child-Pugh score) in the previous six weeks with no data of progressive hepatic insufficiency.
Liver biopsy performed during the previous year showing no liver damage (F0-F1 in the Metavir score) or by elastometry results ≤ 6 Kpa, to classify patients in group B.
Liver cirrhosis guided by biopsy (F4 in the Metavir score) or elastometry: results ≥ 14 Kpa, to classify patients in group A.
Body mass index (BMI) in the range of 19-35 kg/m2.

Key exclusion criteria (9 listed)

HBV surface antigen positive.
Clinical demonstration of a new descompensation event in the previous 6 weeks.
Alcohol abuse as an average daily consumption > 20g.
Treatment with boosted atazanavir, saquinavir or indinavir.
Concomitant treatment with phenytoin, phenobarbital and rifampinor other UGT1A1 inhibitors.

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
Raltegravir 400 mg/12hours	Drug	VIH/VHC coinfected patients without liver damage.
Raltegravir 400 mg/12hours	Drug	Patients with Child-Pugh C hepatic-cirrhosis.

Primary outcome

The area under the curve (AUC0-12) calculated from plasma concentrations, the maximum concentration (Cmax) and the the minimum concentration (Cmin) of Raltegravir 400 mg/12 hours in the steady state for both arms.
Time frame: On the fifth day of treatment with raltegravir
On the fifth day of treatment, patient will be hospitalized in the clinical trial unit in order to obtaine plasma concentrations previous to the administration of the corresponding dose (basal) and at the following times post-administration: 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, and 12h. With these measures, (AUC0-12), Cmax and Cmin will be calculated in order to describe the pharmacokinetic of Raltegravir 400 mgBID in the steady state in both arms

1 secondary outcome

Change from baseline in hematology and biochemistry parameters at day 5 and 15, number of adverse events (serious and non serious) notified and number of patients who discontinue the study (drop-out rate).
Time frame: On day 1, 5 and 15

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2013.
Derived from this study: PubMed 24097843Hernandez-Novoa B, Moreno A, Perez-Elias MJ, Quereda C, Dronda F, Casado JL, Madrid-Elena N, Aguilar M, Fumero E, Molto J, Moreno S. Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). J Antimicrob Chemother. 2014 Feb;69(2):471-5. doi: 10.1093/jac/dkt386. Epub 2013 Oct 4.

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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.

Santiago Moreno Guillen, MD principal investigator

Hospital Universitario Ramón y Cajal. Madrid

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 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 1 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The area under the curve (AUC0-12) calculated from plasma concentrations, the maximum concentration (Cmax) and the the minimum concentration (Cmin) of Raltegravir 400 mg/12 hours in the steady state for both arms. (time frame: On the fifth day of treatment with raltegravir). 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 NCT01289951, which also lists 1 linked publication.

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 1 Feb 2013.