Hepatitis C, ChronicPhase 1NCT01818856
Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir
A Phase 1 study testing Ritonavir withdrawal, atazanavir 200 mg/12h and Telaprevir interactions in people with Hepatitis C, Chronic and HIV Infection, run by Hospitales Universitarios Virgen del Rocío at 1 site in Spain.
Trial summary
Hypothesis: the Telaprevir(TVR) plasma levels (750 mg q8h or 1125 mg/12h )will not be affected when co-administered with un-boosted Atazanavir (ATV) 200 mg q12h plus two analogues (NRTIs) in HCV/HIV-co-infected patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C, Chronic, HIV Infection
- What is being tested?
- Ritonavir withdrawal, atazanavir 200 mg/12h and Telaprevir interactions
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteSpain
- Study dates
- Dec 2012to Apr 2013
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients over 18 years old co-infected with HIV and genotype 1 HCV under treatment with pegylated α-interferon, Ribavirin and Telaprevir according to the recommendations of the Spanish Agency of Medicines and Health Products.
- Informed consent of the patient.
Who cannot join
- The usual exclusion criteria in clinical practice to start the treatment with these drugs (pegylated α-interferon, Ribavirin, Telaprevir and atazanavir) according to the Spanish and international recommendations (Spanish Agency of Medicines and Health Products,European Association for the Study of the Liver Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2011. Consensus Document of Gesida/Spanish Plan on Aids regarding the antiretroviral treatment in adults infected with the human immunodeficiency virus [Updated January 2012]).
- Concomitant use of drugs or medicinal products that could alter the pharmacokinetics of TVR or ATV.
- Medical records suggesting malabsorption or presence of diarrhea (>3 depositions/day) that could interfere with the absorption of the studied drugs.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir in HIV/HCV-co-infected Patients Under Treatment for Genotype 1 Chronic Hepatitis C.
Hypothesis: the Telaprevir(TVR) plasma levels (750 mg q8h or 1125 mg/12h )will not be affected when co-administered with un-boosted Atazanavir (ATV) 200 mg q12h plus two analogues (NRTIs) in HCV/HIV-co-infected patients.
Read the detailed description
Objectives
- Primary Outcome Measures: evaluate the changes in the plasma pharmacokinetic parameters (Cmax, Cmin, AUC, t 1/2, and Cl) of Telaprevir (TVR) administered at 750 mg/8h together with un-boosted Atazanavir (200 mg/12h), taking as reference the pharmacokinetic parameters observed when TVR is administered with Atazanavir/ritonavir (300/100 mg/day)
- To assess the changes in the plasma pharmacokinetic parameters of Atazanavir administered as 200 mg/12h with respect to its administration as 300/100 mg/day when administered together with TVR (750 mg/8h or 1125 mh/12h).
Method: open labelled clinical trial with a planned duration of 24 weeks in which 14 HIV/Hepatitis C virus genotype 1 patients under treatment with pegylated α-interferon, Ribavirin and Telaprevir will be enrolled. A 24 hours pharmacokinetic profile will be obtained after a supervised drug intake while taking TVR and ATV/rtv. Afterwards, the patients will take un-boosted ATV 200 mg bid for 7 - 10 days. Subsequently, a new pharmacokinetic profile will be obtained.
- Conditions
- Hepatitis C, Chronic, HIV Infection
- Being tested
- Ritonavir withdrawal, atazanavir 200 mg/12h, Telaprevir interactions
- Keywords
- Chronic hepatitis C, HIV-infection, Drug interaction
- Medical subject headings
- Hepatitis C, Chronic, HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ritonavir withdrawal, atazanavir 200 mg/12hDrug
Also called Reyataz, Norvir, Incivo
Telaprevir interactionsDrug
Also called Incivo, Reyataz, Norvir
| Study group | Role | What they receive |
|---|---|---|
| Telaprevir interactions | Experimental | Telaprevir 750 mg/8h or 1125 mg/12h (+ pegIFN alfa and ribavirin) plus Atazanavir/ritonavir 300/100 mg/24. Pharmacokinetic profile on day 0.
Intervention: Ritonavir will be withdrawn and the atazanavir dose increased to 200 mg/12h for days 1 to 7. On day 8: a morning dose of Telaprevir (750 mg or 1125 mg) plus Atazanavir 200 mg. Pharmacokinetic profile for 12 hours Receives: Drug: Ritonavir withdrawal, atazanavir 200 mg/12h; Drug: Telaprevir interactions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in pharmacokinetic parameters of TVR
The Telaprevir peak concentrations (Cmax), trough levels (Cmin) at 8 or 12 hours, the areas under the curves over the dosing interval (AUC0-τ), and half-life during the elimination phase (t½ β) will be compared between days 0 and 7 as geometric mean ratios (GMRs) and their 90% CIs using day 0 values as reference. The differences in pharmacokinetic parameters between the regimens will be considered significant when the interval between low and high 90% CI did not include the value 1.0.
Measured: 7 - 10 days
Secondary outcomes (1)
Changes in pharmacokinetic parameters of ATV
The Atazanavir peak concentrations (Cmax), trough levels (Cmin) at 12 or 24 hours, the areas under the curves over the dosing interval (AUC0-τ), and half-life during the elimination phase (t½ β) will be summarized as geometric means (GM) and will be compared between days 0 and 7 as geometric mean ratios (GMRs) and their 90% CIs using day 0 values as reference. The differences in pharmacokinetic parameters between the regimens will be considered significant when the interval between low and high 90% CI did not include the value 1.0.
Measured: 7 - 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2013 (estimated)
- Study startDec 2012
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, ChronicStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospitales Universitarios Virgen del Rocío
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Luis F. Lopez-Cortes, Hospitales Universitarios Virgen del Rocío
- Investigators
- Luis F Lopez-Cortes, MD, PhD., Principal investigator, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla. Spain.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01818856
- Sponsor's protocol ID
- LLC-TEL-2012-1
- Other IDs
- 2012-002515-25
- Status last verified
- Apr 2013
- First submitted
- 29 Dec 2012
- Last updated
- 22 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gutierrez-Valencia A, Ruiz-Valderas R, Ben-Marzouk-Hidalgo OJ, Torres-Cornejo A, Espinosa N, Castillo-Ferrando JR, Viciana P, Lopez-Cortes LF. Telaprevir and ribavirin interaction: higher ribavirin levels are not only due to renal dysfunction during triple therapy. Antimicrob Agents Chemother. 2015;59(6):3257-62. doi: 10.1128/AAC.04795-14. Epub 2015 Mar 23.
PubMed 25801562Gutierrez-Valencia A, Ruiz-Valderas R, Torres-Cornejo A, Viciana P, Espinosa N, Castillo-Ferrando JR, Lopez-Cortes LF. Role of ritonavir in the drug interactions between telaprevir and ritonavir-boosted atazanavir. Clin Infect Dis. 2014 Jan;58(2):268-73. doi: 10.1093/cid/cit693. Epub 2013 Oct 21.
PubMed 24145880
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Interactions Between Telaprevir and Un-boosted Atazanavir in HIV/HCV-co-infected Patients Under Treatment for Genotype 1 Chronic Hepatitis C.
- ClinicalTrials.gov ID
- NCT01818856
- Acronym / sponsor ID
- LLC-TEL-2012-1
- Conditions
- Hepatitis C, Chronic, HIV Infection
- Keywords
- Chronic hepatitis C, HIV-infection, Drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Hospitales Universitarios Virgen del RocíoUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Dec 2012
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 27 Mar 2013 (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.
Hypothesis: the Telaprevir(TVR) plasma levels (750 mg q8h or 1125 mg/12h )will not be affected when co-administered with un-boosted Atazanavir (ATV) 200 mg q12h plus two analogues (NRTIs) in HCV/HIV-co-infected patients.
Detailed description
Objectives
- Primary Outcome Measures: evaluate the changes in the plasma pharmacokinetic parameters (Cmax, Cmin, AUC, t 1/2, and Cl) of Telaprevir (TVR) administered at 750 mg/8h together with un-boosted Atazanavir (200 mg/12h), taking as reference the pharmacokinetic parameters observed when TVR is administered with Atazanavir/ritonavir (300/100 mg/day)
- To assess the changes in the plasma pharmacokinetic parameters of Atazanavir administered as 200 mg/12h with respect to its administration as 300/100 mg/day when administered together with TVR (750 mg/8h or 1125 mh/12h).
Method: open labelled clinical trial with a planned duration of 24 weeks in which 14 HIV/Hepatitis C virus genotype 1 patients under treatment with pegylated α-interferon, Ribavirin and Telaprevir will be enrolled. A 24 hours pharmacokinetic profile will be obtained after a supervised drug intake while taking TVR and ATV/rtv. Afterwards, the patients will take un-boosted ATV 200 mg bid for 7 - 10 days. Subsequently, a new pharmacokinetic profile will be obtained.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Telaprevir interactions | Experimental | Drug: Ritonavir withdrawal, atazanavir 200 mg/12h, Drug: Telaprevir interactionsTelaprevir 750 mg/8h or 1125 mg/12h (+ pegIFN alfa and ribavirin) plus Atazanavir/ritonavir 300/100 mg/24. Pharmacokinetic profile on day 0. Intervention: Ritonavir will be withdrawn and the atazanavir dose increased to 200 mg/12h for days 1 to 7. On day 8: a morning dose of Telaprevir (750 mg or 1125 mg) plus Atazanavir 200 mg. Pharmacokinetic profile for 12 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients over 18 years old co-infected with HIV and genotype 1 HCV under treatment with pegylated α-interferon, Ribavirin and Telaprevir according to the recommendations of the Spanish Agency of Medicines and Health Products.
- Informed consent of the patient.
Key exclusion criteria (3 listed)
- The usual exclusion criteria in clinical practice to start the treatment with these drugs (pegylated α-interferon, Ribavirin, Telaprevir and atazanavir) according to the Spanish and international recommendations (Spanish Agency of Medicines and Health Products,European Association for the Study of the Liver Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2011. Consensus Document of Gesida/Spanish Plan on Aids regarding the antiretroviral treatment in adults infected with the human immunodeficiency virus [Updated January 2012]).
- Concomitant use of drugs or medicinal products that could alter the pharmacokinetics of TVR or ATV.
- Medical records suggesting malabsorption or presence of diarrhea (>3 depositions/day) that could interfere with the absorption of the studied drugs.
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 |
|---|---|---|
| Ritonavir withdrawal, atazanavir 200 mg/12hAlso: Reyataz, Norvir, Incivo | Drug | Telaprevir interactions |
| Telaprevir interactionsAlso: Incivo, Reyataz, Norvir | Drug | Telaprevir interactions |
Primary outcome
Changes in pharmacokinetic parameters of TVR
Time frame: 7 - 10 days
The Telaprevir peak concentrations (Cmax), trough levels (Cmin) at 8 or 12 hours, the areas under the curves over the dosing interval (AUC0-τ), and half-life during the elimination phase (t½ β) will be compared between days 0 and 7 as geometric mean ratios (GMRs) and their 90% CIs using day 0 values as reference. The differences in pharmacokinetic parameters between the regimens will be considered significant when the interval between low and high 90% CI did not include the value 1.0.
1 secondary outcome
Changes in pharmacokinetic parameters of ATV
Time frame: 7 - 10 days
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 22 Apr 2013.
- Derived from this study: PubMed 25801562Gutierrez-Valencia A, Ruiz-Valderas R, Ben-Marzouk-Hidalgo OJ, Torres-Cornejo A, Espinosa N, Castillo-Ferrando JR, Viciana P, Lopez-Cortes LF. Telaprevir and ribavirin interaction: higher ribavirin levels are not only due to renal dysfunction during triple therapy. Antimicrob Agents Chemother. 2015;59(6):3257-62. doi: 10.1128/AAC.04795-14. Epub 2015 Mar 23.
- Derived from this study: PubMed 24145880Gutierrez-Valencia A, Ruiz-Valderas R, Torres-Cornejo A, Viciana P, Espinosa N, Castillo-Ferrando JR, Lopez-Cortes LF. Role of ritonavir in the drug interactions between telaprevir and ritonavir-boosted atazanavir. Clin Infect Dis. 2014 Jan;58(2):268-73. doi: 10.1093/cid/cit693. Epub 2013 Oct 21.
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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.
Luis F Lopez-Cortes, MD, PhD. principal investigator
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla. Spain.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ritonavir withdrawal, atazanavir 200 mg/12h and Telaprevir interactions in people with Hepatitis C, Chronic and HIV Infection, run by Hospitales Universitarios Virgen del Rocío at 1 site 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 2 inclusion and 3 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 22 Apr 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?
Changes in pharmacokinetic parameters of TVR (time frame: 7 - 10 days). 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 NCT01818856, which also lists 2 linked publications.
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 22 Apr 2013.