HIV InfectionsPhase 1NCT00307502

Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV

A Phase 1 study testing Nevirapine, Efavirenz and Indinavir/ritonavir in people with HIV Infections, run by Germans Trias i Pujol Hospital at 6 sites 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

The purpose of this study is to characterise the pharmacokinetic profiles of non-nucleoside analog reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), and the influence of the individual characteristics on the pharmacokinetic parameters in the Spanish population of HIV-infected subjects. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: HIV Infections
What is being tested?: Nevirapine, Efavirenz and Indinavir/ritonavir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 675 participants
Where: 6 sitesSpain
Study dates: Jan 2005to Dec 2009
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 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age higher than 18 years.
Documented HIV infection (at least one positive Western-blot)
Stable antiretroviral treatment with PI or NNRTI, no changes over the last 4 weeks.
Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or negative pregnancy test.

Who cannot join

Subjects on treatment with more than one PI or with combinations of PI and NNRTI (the use of ritonavir in doses below 400 mg BID will not be regarded as a second PI).
Treatment with other drugs with known significant pharmacological interactions with the investigational drug over the previous two weeks.
Unsuitable adherence to treatment (one or more doses omitted in the last week, or two or more doses omitted in the last two weeks).
Presence of clinical findings or a background of gastrointestinal disease or digestive surgery that may interfere in the pharmacokinetics of the medication.
Active consumption of alcohol (>50 grams/day) or illegal drugs (except cannabis).
In the case of women, pregnancy or breastfeeding.
Record or suspicion of inability to cooperate properly

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

Spain6 sites

Germans Trias i Pujol Hospital
Badalona, Barcelona, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital de Figueres
Figueras, Barcelona, 17600
Fundació Hospital-Asil de Granollers
Granollers, Barcelona, 08400
Hospital Universitari Sant Joan de Reus
Reus, Tarragona, 43201
Hospital de Vic
Vic, Barcelona, 08500

Other trials in Spain

About this study

Official title: Cross-sectional Study for the Characterisation of the Pharmacokinetic Parameters of Protease Inhibitors and Non-nucleoside Analog Reverse Transcriptase Inhibitors in the Spanish Population of HIV-infected Subjects

Read the detailed description

The antiretrovirals were administered conventionally according to fixed dosage systems, or depending on the weight of the individual in the case of certain agents. However, the plasma levels of antiretrovirals following the administration of a fixed dose present a marked interindividual variability. Moreover, a significant proportion of the patients on treatment with PIs presented plasma levels regarded as suboptimal in previous studies.

Moreover, for the correct modification of the dosage of a drug, populational data on its pharmacokinetic behaviour during the dosing interval is required. Only by integrating this information with the specific characteristics of each individual is it possible, using mathematical models, to estimate the effect that a modification of the dosage of the drug would have on its plasma concentration. However, populational data on the pharmacokinetic behaviour of antiretroviral agents are still very limited at this moment, and have not always been obtained in populations similar to the one to which they are to be applied.

Thus, knowing the pharmacokinetic behaviour of the antiretroviral agents in our population and the influence of certain individual characteristics on this behaviour may be of great interest, since only in this way will we be able to tailor the dosage of antiretrovirals reliably in our patients.

Conditions: HIV Infections
Being tested: Nevirapine, Efavirenz, Indinavir/ritonavir, Nelfinavir, Saquinavir/ritonavir
Keywords: protease inhibitors, non-nucleoside analog reverse transcriptase inhibitors, pharmacokinetic models, treatment experienced, HIV
Medical subject headings: HIV Infections

What participants receive

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

NevirapineDrug
Also called Viramune
tablets 200 mg, 400 mg/day
EfavirenzDrug
Also called Sustiva
tablets 600 mg, 600 mg/day
Indinavir/ritonavirDrug
Also called Crixivan/norvir
Indinavir: capsules 400 mg, 1600 mg/day
Ritonavir: capsules 100 mg, 200 mg/day
NelfinavirDrug
Also called Viracept
tablets 250 mg, 2500 mg/day
Saquinavir/ritonavirDrug
Also called Invirase/Norvir
Saquinavir: tablets 500 mg, 2000 mg/day
Ritonavir: tablets 100 mg, 200 mg/day
Lopinavir/ritonavirDrug
Also called Kaletra
tablets lopinavir 200 mg + ritonavir 50 mg, 800/200 mg/day
AtazanavirDrug
Also called Reyataz
capsules 200 mg, 400 mg/day
Atazanavir/ritonavirDrug
Also called Reyataz/Norvir
Atazanavir: capsules 150 mg, 300 mg/day
Ritonavir: capsules 100 mg, 200 mg/day
Fos-amprenavir/ritonavirDrug
Also called Telzir/norvir
Fos-amprenavir: capsules 700 mg, 1400 mg/day
Ritonavir: capsules 100 mg, 200 mg/day
Tipranavir/ ritonavirDrug
Also called Aptivus/Norvir
Tipranavir: tablets 250 mg, 1000 mg/day
Ritonavir: capsules 100 mg, 400 mg/day
Darunavir/ritonavirDrug
Also called Prezista/norvir
Darunavir: tablets 300 mg, 1200 mg/day
Ritonavir: capsules 100 mg, 200 mg/day

Study groups in NCT00307502
Study group	Role	What they receive
NVP	Experimental	Nevirapine Receives: Drug: Nevirapine
EFV	Experimental	Efavirenz Receives: Drug: Efavirenz
INV	Experimental	Indinavir/ritonavir Receives: Drug: Indinavir/ritonavir
NFV	Experimental	Nelfinavir Receives: Drug: Nelfinavir
SQV	Experimental	Saquinavir/ritonavir Receives: Drug: Saquinavir/ritonavir
LPV	Experimental	Lopinavir/ritonavir Receives: Drug: Lopinavir/ritonavir
ATV	Experimental	Atazanavir Receives: Drug: Atazanavir
ATV/rtv	Experimental	Atazanavir/ritonavir Receives: Drug: Atazanavir/ritonavir
Fos-APV	Experimental	Fos-amprenavir/ritonavir Receives: Drug: Fos-amprenavir/ritonavir
TPV	Experimental	Tipranavir/ritonavir Receives: Drug: Tipranavir/ ritonavir
DRV	Experimental	Darunavir/ritonavir Receives: Drug: Darunavir/ritonavir

What is being measured

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

The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).
Measured: In the 12 hour (h) pharmacokinetic curve

Secondary outcomes (7)

Demographic: race, gender, age
Measured: In the 12 h pharmacokinetic curve
Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption
Measured: In the 12 h pharmacokinetic curve
Adverse events
Measured: In the 12 h pharmacokinetic curve
Laboratory: creatinine, albumin, Quick Index, bilirubin, GOT, GPT, GGT, FA, CD4 lymphocyte count, HIV viral load, HBsAg and anti-HCV, alpha acid glycoprotein
Measured: In the 12 h pharmacokinetic curve
Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks)
Measured: In the 12 h pharmacokinetic curve
Pharmacokinetics: maximum concentration (Cmax), time to maximum concentration (Tmax), plasma concentration at the end of the posology interval (Ctrough), half-life (T1/2), area under the curve (ABC)
Measured: In the 12 h pharmacokinetic curve
Genetic study of polymorphism of CYP3A4 and P-glycoprotein
Measured: In the 12 h pharmacokinetic curve

Timeline

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

Jan 2005Dec 2009

First posted28 Mar 2006 (estimated)
Study startJan 2005
Primary completionDec 2009
Study completionDec 2009

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 HIV InfectionsStudies 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: Single group
Masking: None (open label)
Enrolment: 675 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00307502
Sponsor's protocol ID: PK-TRANSVERSAL
Other IDs: 2004-001516-32, 2004
Status last verified: Dec 2019
First submitted: 27 Mar 2006
Last updated: 4 Dec 2019
Results posted: No
Data monitoring committee: No

Publications

Molto J, Xinarianos G, Miranda C, Pushpakom S, Cedeno S, Clotet B, Owen A, Valle M. Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients. Clin Pharmacokinet. 2013 Jul;52(7):543-53. doi: 10.1007/s40262-013-0057-6.
PubMed 23494984

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 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cross-sectional Study for the Characterisation of the Pharmacokinetic Parameters of Protease Inhibitors and Non-nucleoside Analog Reverse Transcriptase Inhibitors in the Spanish Population of HIV-infected Subjects
ClinicalTrials.gov ID: NCT00307502
Acronym / sponsor ID: PK-TRANSVERSAL
Conditions: HIV Infections
Keywords: protease inhibitors, non-nucleoside analog reverse transcriptase inhibitors, pharmacokinetic models, treatment experienced, HIV
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 675 participants (actual)
Lead sponsor: Germans Trias i Pujol HospitalUniversity, hospital or other
Collaborators: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Study start: Jan 2005
Primary completion: Dec 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 28 Mar 2006 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 11

Arm	Type	Receives
NVP	Experimental	Drug: NevirapineNevirapine
EFV	Experimental	Drug: EfavirenzEfavirenz
INV	Experimental	Drug: Indinavir/ritonavirIndinavir/ritonavir
NFV	Experimental	Drug: NelfinavirNelfinavir
SQV	Experimental	Drug: Saquinavir/ritonavirSaquinavir/ritonavir
LPV	Experimental	Drug: Lopinavir/ritonavirLopinavir/ritonavir
ATV	Experimental	Drug: AtazanavirAtazanavir
ATV/rtv	Experimental	Drug: Atazanavir/ritonavirAtazanavir/ritonavir
Fos-APV	Experimental	Drug: Fos-amprenavir/ritonavirFos-amprenavir/ritonavir
TPV	Experimental	Drug: Tipranavir/ ritonavirTipranavir/ritonavir
DRV	Experimental	Drug: Darunavir/ritonavirDarunavir/ritonavir

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Age higher than 18 years.
Documented HIV infection (at least one positive Western-blot)
Stable antiretroviral treatment with PI or NNRTI, no changes over the last 4 weeks.
Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or negative pregnancy test.

Key exclusion criteria (7 listed)

Subjects on treatment with more than one PI or with combinations of PI and NNRTI (the use of ritonavir in doses below 400 mg BID will not be regarded as a second PI).
Treatment with other drugs with known significant pharmacological interactions with the investigational drug over the previous two weeks.
Unsuitable adherence to treatment (one or more doses omitted in the last week, or two or more doses omitted in the last two weeks).
Presence of clinical findings or a background of gastrointestinal disease or digestive surgery that may interfere in the pharmacokinetics of the medication.
Active consumption of alcohol (>50 grams/day) or illegal drugs (except cannabis).

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
NevirapineAlso: Viramunetablets 200 mg, 400 mg/day	Drug	NVP
EfavirenzAlso: Sustivatablets 600 mg, 600 mg/day	Drug	EFV
Indinavir/ritonavirAlso: Crixivan/norvirIndinavir: capsules 400 mg, 1600 mg/day Ritonavir: capsules 100 mg, 200 mg/day	Drug	INV
NelfinavirAlso: Viracepttablets 250 mg, 2500 mg/day	Drug	NFV
Saquinavir/ritonavirAlso: Invirase/NorvirSaquinavir: tablets 500 mg, 2000 mg/day Ritonavir: tablets 100 mg, 200 mg/day	Drug	SQV
Lopinavir/ritonavirAlso: Kaletratablets lopinavir 200 mg + ritonavir 50 mg, 800/200 mg/day	Drug	LPV
AtazanavirAlso: Reyatazcapsules 200 mg, 400 mg/day	Drug	ATV
Atazanavir/ritonavirAlso: Reyataz/NorvirAtazanavir: capsules 150 mg, 300 mg/day Ritonavir: capsules 100 mg, 200 mg/day	Drug	ATV/rtv
Fos-amprenavir/ritonavirAlso: Telzir/norvirFos-amprenavir: capsules 700 mg, 1400 mg/day Ritonavir: capsules 100 mg, 200 mg/day	Drug	Fos-APV
Tipranavir/ ritonavirAlso: Aptivus/NorvirTipranavir: tablets 250 mg, 1000 mg/day Ritonavir: capsules 100 mg, 400 mg/day	Drug	TPV
Darunavir/ritonavirAlso: Prezista/norvirDarunavir: tablets 300 mg, 1200 mg/day Ritonavir: capsules 100 mg, 200 mg/day	Drug	DRV

Primary outcome

The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).
Time frame: In the 12 hour (h) pharmacokinetic curve

7 secondary outcomes

Demographic: race, gender, age
Time frame: In the 12 h pharmacokinetic curve
Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption
Time frame: In the 12 h pharmacokinetic curve
Adverse events
Time frame: In the 12 h pharmacokinetic curve
Laboratory: creatinine, albumin, Quick Index, bilirubin, GOT, GPT, GGT, FA, CD4 lymphocyte count, HIV viral load, HBsAg and anti-HCV, alpha acid glycoprotein
Time frame: In the 12 h pharmacokinetic curve
Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks)
Time frame: In the 12 h pharmacokinetic curve
Pharmacokinetics: maximum concentration (Cmax), time to maximum concentration (Tmax), plasma concentration at the end of the posology interval (Ctrough), half-life (T1/2), area under the curve (ABC)
Time frame: In the 12 h pharmacokinetic curve
Genetic study of polymorphism of CYP3A4 and P-glycoprotein
Time frame: In the 12 h pharmacokinetic curve

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 4 Dec 2019.
Derived from this study: PubMed 23494984Molto J, Xinarianos G, Miranda C, Pushpakom S, Cedeno S, Clotet B, Owen A, Valle M. Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients. Clin Pharmacokinet. 2013 Jul;52(7):543-53. doi: 10.1007/s40262-013-0057-6.

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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.

Bonaventura Clotet, MD, PhD principal investigator

Lluita contra la Sida Foundation-HIV Unit

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nevirapine, Efavirenz and Indinavir/ritonavir in people with HIV Infections, run by Germans Trias i Pujol Hospital at 6 sites in Spain.

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 7 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 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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 primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution). (time frame: In the 12 hour (h) pharmacokinetic curve). 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 NCT00307502, 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 4 Dec 2019.