HIV InfectionPhase 1Emend-IVNCT02154360
Pharmacokinetic Characteristics and Anti-Inflammatory Effects of Aprepitant In HIV-Infected Subjects
A Phase 1 study testing Aprepitant in people with HIV Infection, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is an open-label, single arm, phase I study to determine the safety, PK characteristics and anti-inflammatory effects of the NK-R1 coadministered with ritonavir-containing antiretroviral therapy in individuals with well-controlled viral replication. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Aprepitant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Jun 2016
- 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
- HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
- Antiretroviral treatment with a regimen that includes either atazanavir 300 mg daily with ritonavir 100 mg daily or darunavir/ritonavir on a combination of 800/100 mg daily for at least 6 months prior to enrollment.
- CD4+ cell count ≥ 350/mm3 for at least 6 months prior to enrollment and performed at any CLIA-certified laboratory.
- Plasma HIV-1 RNA below the limit of quantification of an ultrasensitive assay as measured by any standard assay (the Roche Amplicor, the UltraSensitive HIV-1 Monitor assay (Roche Molecular Systems), or Version 3 bDNA assay or other) for at least 6 months prior to enrollment by any laboratory that is CLIA-certified (or its equivalent) for the assay.
- Laboratory values obtained within 30 days prior to study entry, as follows:
- Absolute neutrophil count (ANC) greater or equal than 750/mm3
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- Hemoglobin greater or equal than 10.0 g/dL
- Platelet count greater or equal than 100,000/mm3
- Creatinine less or equal than 2 x ULN (fasting)
- AST (SGOT), ALT (SGPT), and alkaline phosphatase less or equal than 2 x ULN
- Total bilirubin less or equal than 2.5 x ULN
- Albumin greater or equal than 3 g/dL
- Female subjects of reproductive potential must have a negative spot urine pregnancy test result (with a sensitivity of at least 50 mIU/mL) performed at entry, prior to starting initial study treatment.
- All subjects must agree not to participate in a conception process while on study drug and for 30 days after stopping the medication.
- If participating in sexual activity that could lead to pregnancy, the female study subject must use at least one of the forms of contraception listed below while receiving the protocol-specified medication and for 30 days after stopping the medication.
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- IUD
- Female subjects, who are not of reproductive potential defined as women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization, (e.g. hysterectomy, bilateral oophorectomy, or salpingotomy) are eligible without requiring the use of contraception. Subject reported history is acceptable for documentation of sterilization, other contraceptive methods, menopause and a female's reproductive potential.
- Karnofsky performance score greater or equal than 80 within 30 days prior to study entry (Appendix I).
- Men and women greater or equal than 18 years of age.
- Ability and willingness of subject or legal guardian/representative to give written informed consent.
- Willing to return for a follow-up visit on day 58.
- Subjects taking any precautionary concomitant medications must be on stable doses for >8 weeks prior to study entry and have no plans to change medications or doses for the duration of the study.
Who cannot join
- Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
- Pregnancy within 90 days prior to study entry.
- Use of inhibitors of metabolism by the cytochrome P450 3A4 with the exception of ritonavir, atazanavir and darunavir (i.e. Diltiazem, Ketoconazole, Clarithromycin, Nelfinavir, Itraconazole, Nefazodone, Troleandomycin)
- Use of inducers of metabolism by the cytochrome P450 3A4 (i.e.: Rifampin, Carbamazepine, Phenytoin) with the exception of the protease inhibitors considered in this trial.
- Breast-feeding.
- Use of systemic corticosteroids or hormonal agents within 90 days prior to study entry.
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- Use of any immunomodulator, HIV vaccines, or investigational therapy within 90 days prior to study entry. However, if the experimental agent has a short half life, as determined by the Principal Investigator, the required wash out period can be reduced to 30 days.
- Any vaccination within 30 days prior to study entry.
- Use of systemic cytotoxic chemotherapy within 90 days prior to study entry.
- History of allergy to aprepitant or its formulations.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- History of chronic active hepatitis B or C infection or severe hepatic dysfunction (Child-Pugh score > 9) regardless of etiology
- Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 14 days prior to study entry.
- Weight < 40 kg or 88 lbs. within 90 days prior to study entry.
- History of severe psychiatric comorbidities, such as depression, schizophrenia, mania, psychosis
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania Clinical Research Site
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase IB, Open Label Study to Examine the Safety, Pharmacokinetic Characteristics and Anti-Inflammatory Effects of the NK-1R Antagonist, Aprepitant, In HIV-Infected Subjects Receiving Atazanavir/Ritonavir Or Darunavir/Ritonavir
This is an open-label, single arm, phase I study to determine the safety, PK characteristics and anti-inflammatory effects of the NK-R1 coadministered with ritonavir-containing antiretroviral therapy in individuals with well-controlled viral replication.
Our hypothesis is that Aprepitant will be safe, well tolerated, and will have anti-inflammatory properties when administered concomitantly with the protease inhibitor ritonavir.
Read the detailed description
This is an open-label, single arm, phase I study to determine the safety, PK characteristics and anti-inflammatory effects of the NK-R1 coadministered with ritonavir-containing antiretroviral therapy in individuals with well-controlled viral replication.
Our hypothesis is that Aprepitant will be safe, well tolerated, and will have anti-inflammatory properties when administered concomitantly with the protease inhibitor ritonavir. The study will recruit 12 participants receiving either darunavir/ritonavir or atazanavir/ritonavir
- Conditions
- HIV Infection
- Being tested
- Aprepitant
- Keywords
- HIV infection, NK-1R antagonists, aprepitant, ritonavir boosting
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AprepitantDrug
Also called Emend
Subjects will add 375 mg daily dosing of aprepitant (Emend®) to their current antiretroviral therapy for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Aprepitant | Experimental | Subjects will add 375 mg daily dosing of aprepitant (Emend®) to their current antiretroviral therapy for 28 days.
* 6 participants will be receiving an antiretroviral regimen containing atazanavir/ritonavir (300/100 mg) daily plus two other antiretrovirals.
* 6 participants will be receiving an antiretroviral regimen containing darunavir/ritonavir (800/100 mg) daily plus two other antiretrovirals. Receives: Drug: Aprepitant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammatory
Change in levels of Soluble CD163 from baseline to Day 14.
Measured: 14 days
Safety
Incidence of Grade 2, 3, and 4 adverse events (using the DAIDS grading scale) by body system and by type. Lack of virologic control is considered a safety event for the purpose of this trial.
Measured: 28 days
Pharmacokinetic Cmin:
Trough plasma aprepitant concentration.
Measured: day 1, 14 and 28
Pharmacokinetic Cmax
Maximum plasma concentration.
Measured: day 1, 14 and 28
Pharmacokinetic Tmax
Time to maximum plasma concentration
Measured: day 1, 14 and 28
Pharmacokinetic AUCss
Area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).
Measured: day 1, 14 and 28
Secondary outcomes (3)
Inflammatory markers
- Change in levels of Soluble CD163 from baseline to Day 28 and 58
- Plasma SP levels
- CD4/PD-1 expression
Measured: 28 days
Lipids
- Triglycerides
- Total cholesterol
- HDL
- LDL
- Insulin
Measured: 28 days
Neurological
- Hamilton-17 Depression Rating Scale (HAM-D-17) score
- Hamilton- Anxiety Symptoms (HAM-A) score
- Pittsburgh Sleep Quality Index (PSQI) score
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2014 (estimated)
- Study startMay 2014
- Primary completionDec 2015
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pablo Tebas, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02154360
- Sponsor's protocol ID
- UPenn 819693
- Acronym
- Emend-IV
- Status last verified
- Aug 2017
- First submitted
- 22 May 2014
- Last updated
- 17 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tebas P, Tuluc F, Barrett JS, Wagner W, Kim D, Zhao H, Gonin R, Korelitz J, Douglas SD. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults. PLoS One. 2011;6(9):e24180. doi: 10.1371/journal.pone.0024180. Epub 2011 Sep 8.
PubMed 21931661Manak MM, Moshkoff DA, Nguyen LT, Meshki J, Tebas P, Tuluc F, Douglas SD. Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS. 2010 Nov 27;24(18):2789-96. doi: 10.1097/QAD.0b013e3283405c33.
PubMed 20975512Wang X, Douglas SD, Lai JP, Tuluc F, Tebas P, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) inhibits drug-resistant HIV-1 infection of macrophages in vitro. J Neuroimmune Pharmacol. 2007 Mar;2(1):42-8. doi: 10.1007/s11481-006-9059-6. Epub 2007 Jan 12.
PubMed 18040825Spitsin S, Tebas P, Barrett JS, Pappa V, Kim D, Taylor D, Evans DL, Douglas SD. Antiinflammatory effects of aprepitant coadministration with cART regimen containing ritonavir in HIV-infected adults. JCI Insight. 2017 Oct 5;2(19):e95893. doi: 10.1172/jci.insight.95893.
PubMed 28978797
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB, Open Label Study to Examine the Safety, Pharmacokinetic Characteristics and Anti-Inflammatory Effects of the NK-1R Antagonist, Aprepitant, In HIV-Infected Subjects Receiving Atazanavir/Ritonavir Or Darunavir/Ritonavir
- ClinicalTrials.gov ID
- NCT02154360
- Acronym / sponsor ID
- Emend-IV / UPenn 819693
- Conditions
- HIV Infection
- Keywords
- HIV infection, NK-1R antagonists, aprepitant, ritonavir boosting
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 3 Jun 2014 (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.
This is an open-label, single arm, phase I study to determine the safety, PK characteristics and anti-inflammatory effects of the NK-R1 coadministered with ritonavir-containing antiretroviral therapy in individuals with well-controlled viral replication.
Our hypothesis is that Aprepitant will be safe, well tolerated, and will have anti-inflammatory properties when administered concomitantly with the protease inhibitor ritonavir.
Detailed description
This is an open-label, single arm, phase I study to determine the safety, PK characteristics and anti-inflammatory effects of the NK-R1 coadministered with ritonavir-containing antiretroviral therapy in individuals with well-controlled viral replication.
Our hypothesis is that Aprepitant will be safe, well tolerated, and will have anti-inflammatory properties when administered concomitantly with the protease inhibitor ritonavir. The study will recruit 12 participants receiving either darunavir/ritonavir or atazanavir/ritonavir
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aprepitant | Experimental | Drug: AprepitantSubjects will add 375 mg daily dosing of aprepitant (Emend®) to their current antiretroviral therapy for 28 days. * 6 participants will be receiving an antiretroviral regimen containing atazanavir/ritonavir (300/100 mg) daily plus two other antiretrovirals. * 6 participants will be receiving an antiretroviral regimen containing darunavir/ritonavir (800/100 mg) daily plus two other antiretrovirals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
- Antiretroviral treatment with a regimen that includes either atazanavir 300 mg daily with ritonavir 100 mg daily or darunavir/ritonavir on a combination of 800/100 mg daily for at least 6 months prior to enrollment.
- CD4+ cell count ≥ 350/mm3 for at least 6 months prior to enrollment and performed at any CLIA-certified laboratory.
- Plasma HIV-1 RNA below the limit of quantification of an ultrasensitive assay as measured by any standard assay (the Roche Amplicor, the UltraSensitive HIV-1 Monitor assay (Roche Molecular Systems), or Version 3 bDNA assay or other) for at least 6 months prior to enrollment by any laboratory that is CLIA-certified (or its equivalent) for the assay.
- Laboratory values obtained within 30 days prior to study entry, as follows:
Key exclusion criteria (15 listed)
- Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
- Pregnancy within 90 days prior to study entry.
- Use of inhibitors of metabolism by the cytochrome P450 3A4 with the exception of ritonavir, atazanavir and darunavir (i.e. Diltiazem, Ketoconazole, Clarithromycin, Nelfinavir, Itraconazole, Nefazodone, Troleandomycin)
- Use of inducers of metabolism by the cytochrome P450 3A4 (i.e.: Rifampin, Carbamazepine, Phenytoin) with the exception of the protease inhibitors considered in this trial.
- Breast-feeding.
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 |
|---|---|---|
| AprepitantAlso: EmendSubjects will add 375 mg daily dosing of aprepitant (Emend®) to their current antiretroviral therapy for 28 days | Drug | Aprepitant |
Primary outcome
Inflammatory
Time frame: 14 days
Change in levels of Soluble CD163 from baseline to Day 14.
Safety
Time frame: 28 days
Incidence of Grade 2, 3, and 4 adverse events (using the DAIDS grading scale) by body system and by type. Lack of virologic control is considered a safety event for the purpose of this trial.
Pharmacokinetic Cmin:
Time frame: day 1, 14 and 28
Trough plasma aprepitant concentration.
Pharmacokinetic Cmax
Time frame: day 1, 14 and 28
Maximum plasma concentration.
Pharmacokinetic Tmax
Time frame: day 1, 14 and 28
Time to maximum plasma concentration
Pharmacokinetic AUCss
Time frame: day 1, 14 and 28
Area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).
3 secondary outcomes
Inflammatory markers
Time frame: 28 days
Lipids
Time frame: 28 days
Neurological
Time frame: 28 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 17 Aug 2017.
- Background: PubMed 21931661Tebas P, Tuluc F, Barrett JS, Wagner W, Kim D, Zhao H, Gonin R, Korelitz J, Douglas SD. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults. PLoS One. 2011;6(9):e24180. doi: 10.1371/journal.pone.0024180. Epub 2011 Sep 8.
- Background: PubMed 20975512Manak MM, Moshkoff DA, Nguyen LT, Meshki J, Tebas P, Tuluc F, Douglas SD. Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS. 2010 Nov 27;24(18):2789-96. doi: 10.1097/QAD.0b013e3283405c33.
- Background: PubMed 18040825Wang X, Douglas SD, Lai JP, Tuluc F, Tebas P, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) inhibits drug-resistant HIV-1 infection of macrophages in vitro. J Neuroimmune Pharmacol. 2007 Mar;2(1):42-8. doi: 10.1007/s11481-006-9059-6. Epub 2007 Jan 12.
- Derived from this study: PubMed 28978797Spitsin S, Tebas P, Barrett JS, Pappa V, Kim D, Taylor D, Evans DL, Douglas SD. Antiinflammatory effects of aprepitant coadministration with cART regimen containing ritonavir in HIV-infected adults. JCI Insight. 2017 Oct 5;2(19):e95893. doi: 10.1172/jci.insight.95893.
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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.
Pablo Tebas, MD principal investigator
University of Pennsylvania
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 Aprepitant in people with HIV Infection, run by University of Pennsylvania at 1 site in United States.
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 24 inclusion and 15 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 17 Aug 2017. 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 United States. 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?
Inflammatory (time frame: 14 days). The study lists 6 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 NCT02154360, which also lists 4 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 17 Aug 2017; AzTrials last refreshed its copy on 8 Nov 2026.