HIV InfectionPhase 1NCT01300988
Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals. 375 mg Dose
A Phase 1 study testing Aprepitant in people with HIV Infection, run by University of Pennsylvania at 1 site in United States.
Trial summary
The investigators' in vitro data suggest that Neurokinin-1 receptor antagonists like aprepitant will decrease the expression of CCR5, an essential co-receptor in the life cycle of HIV, in the surface of macrophages and lymphocytes to levels at least similar to those observed in patients heterozygous for the CCR5 32… 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?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Aug 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, as documented by a rapid HIV test or any FDA-Approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test kit and confirmed by Western blot at any time prior to study entry.
- CD4+ cell count >= 350/mm3 obtained within 90 days prior to study entry
- Plasma HIV-1 RNA of >=2,000 copies/mL as measured by any standard assay and performed within 90 days prior to study entry.
- CCR5 tropic virus exclusively as determined by the Monogram tropism assay (PhenoSense Entry™) to be performed within 90 days of study entry.
- Laboratory values obtained within 30 days prior to study entry, as follows:
- Absolute neutrophil count (ANC) >= 750/mm3
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- Hemoglobin >= 10.0 g/dL
- Platelet count >= 100,000/mm3
- Creatinine <= 2 x ULN
- AST (SGOT), ALT (SGPT), and alkaline phosphatase <= 2 x ULN
- Total bilirubin <= 2.5 x ULN
- Albumin >= 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.
- Karnofsky performance score >= 80 within 30 days prior to study entry.
- Men and women > 18 years of age.
- Ability and willingness of subject to give written informed consent.
- Willing to return for a follow-up visit on day 42.
- 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
- Receipt of antiretroviral treatment within the 16 weeks prior to study entry or intent to initiate antiretroviral therapy within 60 days after entry.
- Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
- Pregnancy within 90 days prior to study entry.
- Breast-feeding.
- Use of drugs that are inhibitors or inducers of metabolism by the cytochrome P450 CYP3A4 or CYP2C9 (such as warfarin and phenytoin) within 7 days of study entry.
- Use of systemic corticosteroids or hormonal agents within 90 days prior to study entry.
Show all 15Show fewer
- Use of any immunomodulator, HIV vaccines, or investigational therapy within 90 days prior to study entry.
- 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
Clinical Trials Unit. University of Pennsylvania
Philadelphia, Pennsylvania, 19104--607
About this study
Official title: A Phase Ib, Randomized, Placebo Controlled, Double Blind Study to Determine the Safety, Viral Suppression, Pharmacokinetics and Immune Modulatory Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals
The investigators' in vitro data suggest that Neurokinin-1 receptor antagonists like aprepitant will decrease the expression of CCR5, an essential co-receptor in the life cycle of HIV, in the surface of macrophages and lymphocytes to levels at least similar to those observed in patients heterozygous for the CCR5 32 mutation. Together with a direct potential antiviral effect this could alter disease progression in patients with HIV infection.
The investigators' hypothesis is that aprepitant is safe, tolerable and has antiviral activity in HIV infected individuals.
Read more
This is randomized, placebo controlled, double blind study to determine the safety and antiviral activity of aprepitant by comparing the change in HIV RNA viral load after 2 weeks of aprepitant monotherapy.
18 HIV infected males and females ≥ 18 years old who have early infection with CD4 cell counts ≥ 350 cells/mm3. Subjects will be randomized 1:1 to receive 375 mg of aprepitant (Emend®) or placebo.
Read the detailed description
DESIGN
Randomized, placebo controlled, double blind study to determine the safety and antiviral activity of aprepitant by comparing the change in HIV RNA viral load after 2 weeks of aprepitant monotherapy.
DURATION
42 days.
SAMPLE SIZE and POPULATION
18 HIV infected males and females ≥ 18 years old who have early infection with CD4 cell counts ≥ 350 cells/mm3.
REGIMEN
Subjects will be randomized 1:1 to receive aprepitant (Emend®) or placebo.
Arm A: Aprepitant placebo Arm B: Aprepitant 375 mg QD
HYPOTHESIS AND STUDY OBJECTIVES
Hypothesis : Aprepitant is safe, tolerable, and has antiviral activity in HIV infected individuals.
Primary Objectives:
To assess the safety and tolerability of 375 mg aprepitant for 2 weeks To assess the response of plasma HIV-1 RNA to 375 mg of aprepitant compared with baseline.
Secondary Objectives:
To investigate the course and duration of antiretroviral response 375 mg of aprepitant given over a 14-day period.
To evaluate the dose-response and pharmacokinetic and pharmacodynamic relationship between viral RNA change and aprepitant plasma levels.
To evaluate aprepitant effects on CD4+ and CD8+ T-cell counts, circulating SP levels, natural killer cell number and function and CCR5 expression in peripheral PBMCs.
To evaluate the effects of aprepitant in the viral tropism and envelope sequence of the main HIV-1 population of the participants.
To assess viral drug susceptibility in conjunction with baseline coreceptor tropism phenotype and changes in coreceptor phenotype after the exposure to aprepitant.
To evaluate aprepitant effects on fasting plasma glucose, insulin, HDL, free fatty acids, and triglyceride concentrations after 14 days of treatment.
To provide preliminary description of any change from baseline in sleep quality, anxious mood, depressed mood and neurocognitive measures after 2 weeks of aprepitant therapy.
- Conditions
- HIV Infection
- Being tested
- Aprepitant, Aprepitant placebo
- Keywords
- HIV infection, Neurokinin-1 receptor antagonist, CCR5 expression, 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.
AprepitantDrug
Aprepitant (Emend®) 375 mg daily for 14 days
Aprepitant placeboDrug
Aprepitant(Emend®) placebo for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Aprepitant | Active comparator | Aprepitant (Emend®) 375 mg daily for 14 days Receives: Drug: Aprepitant |
| Placebo | Placebo comparator | Aprepitant (Emend®) placebo for 14 days Receives: Drug: Aprepitant placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virologic: Change in log10 HIV-1 RNA from baseline to Day 14
For the purposes of assessing the primary analysis of efficacy of aprepitant in reducing viral load we will be assessing the difference between the log10 viral load at baseline and at 4 weeks, and constructing a 95% confidence interval around this mean difference within each dose group.
Measured: 14 days
Safety: Incidence of Grade 2, 3, and 4 adverse events
The frequency of grade 2,3 and 4 adverse events for the duration of the study will be measured to assess the safety of the compund in this population. Exact binomial confidence intervals will be calculated around the event rates for any individual adverse events that occur and for the overall rate of adverse events within each body system. For each patient the highest grade occurring adverse event within each body system will be assessed. Tables for adverse events by body system and severity of adverse event will be constructed.
Measured: 42 days
Secondary outcomes (3)
Pharmacokinetic
Individual patient data will be summarized using a noncompartmental analysis (NCA) approach as well as a model-based approach.
Measured: 14 days
Immunologic
A descriptive analysis of the following parameters by arm at each time point will be done:
- CCR5 mRNA copy number per cell and CCR5 density by flow cytometry.
- CD4+ cell count at baseline, Days 3, 7, 10, 14, and 42.
- Time to permanent discontinuation of study treatment for any reason.
- Baseline coreceptor phenotype (CCR5, CXCR4, or mixed).
- Time to change from CCR5-only virus to mixed CCR5/CXCR4 or CXCR4-only virus as detected by the phenotype/genotype assays that will be used in this study.
Measured: 14 days
Neurologic
Evaluate individual changes from baseline to 14 days for these subjects in the HAM-D 17 Depression Rating Scale score, the HAM-A, and the PSQI
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2011 (estimated)
- Study startDec 2010
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Pablo Tebas, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01300988
- Sponsor's protocol ID
- 811938
- Other IDs
- U01MH090325
- Status last verified
- Jun 2016
- First submitted
- 16 Dec 2010
- Last updated
- 3 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lai JP, Ho WZ, Zhan GX, Yi Y, Collman RG, Douglas SD. Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3970-5. doi: 10.1073/pnas.071052298.
PubMed 11274418Lai JP, Ho WZ, Kilpatrick LE, Wang X, Tuluc F, Korchak HM, Douglas SD. Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7771-6. doi: 10.1073/pnas.0602563103. Epub 2006 May 4.
PubMed 16675550Ho WZ, Evans DL, Douglas SD. Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology. CNS Spectr. 2002 Dec;7(12):867-874. doi: 10.1017/s1092852900022483.
PubMed 12766696Ho WZ, Lai JP, Li Y, Douglas SD. HIV enhances substance P expression in human immune cells. FASEB J. 2002 Apr;16(6):616-8. doi: 10.1096/fj.01-0655fje.
PubMed 11919172Li Y, Douglas SD, Song L, Sun S, Ho WZ. Substance P enhances HIV-1 replication in latently infected human immune cells. J Neuroimmunol. 2001 Dec 3;121(1-2):67-75. doi: 10.1016/s0165-5728(01)00439-8.
PubMed 11730941
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Randomized, Placebo Controlled, Double Blind Study to Determine the Safety, Viral Suppression, Pharmacokinetics and Immune Modulatory Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals
- ClinicalTrials.gov ID
- NCT01300988
- Acronym / sponsor ID
- 811938
- Conditions
- HIV Infection
- Keywords
- HIV infection, Neurokinin-1 receptor antagonist, CCR5 expression, Treatment Naive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Dec 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 23 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.
The investigators' in vitro data suggest that Neurokinin-1 receptor antagonists like aprepitant will decrease the expression of CCR5, an essential co-receptor in the life cycle of HIV, in the surface of macrophages and lymphocytes to levels at least similar to those observed in patients heterozygous for the CCR5 32 mutation. Together with a direct potential antiviral effect this could alter disease progression in patients with HIV infection.
The investigators' hypothesis is that aprepitant is safe, tolerable and has antiviral activity in HIV infected individuals.
This is randomized, placebo controlled, double blind study to determine the safety and antiviral activity of aprepitant by comparing the change in HIV RNA viral load after 2 weeks of aprepitant monotherapy.
18 HIV infected males and females ≥ 18 years old who have early infection with CD4 cell counts ≥ 350 cells/mm3. Subjects will be randomized 1:1 to receive 375 mg of aprepitant (Emend®) or placebo.
Detailed description
DESIGN
Randomized, placebo controlled, double blind study to determine the safety and antiviral activity of aprepitant by comparing the change in HIV RNA viral load after 2 weeks of aprepitant monotherapy.
DURATION
42 days.
SAMPLE SIZE and POPULATION
18 HIV infected males and females ≥ 18 years old who have early infection with CD4 cell counts ≥ 350 cells/mm3.
REGIMEN
Subjects will be randomized 1:1 to receive aprepitant (Emend®) or placebo.
Arm A: Aprepitant placebo Arm B: Aprepitant 375 mg QD
HYPOTHESIS AND STUDY OBJECTIVES
Hypothesis : Aprepitant is safe, tolerable, and has antiviral activity in HIV infected individuals.
Primary Objectives:
To assess the safety and tolerability of 375 mg aprepitant for 2 weeks To assess the response of plasma HIV-1 RNA to 375 mg of aprepitant compared with baseline.
Secondary Objectives:
To investigate the course and duration of antiretroviral response 375 mg of aprepitant given over a 14-day period.
To evaluate the dose-response and pharmacokinetic and pharmacodynamic relationship between viral RNA change and aprepitant plasma levels.
To evaluate aprepitant effects on CD4+ and CD8+ T-cell counts, circulating SP levels, natural killer cell number and function and CCR5 expression in peripheral PBMCs.
To evaluate the effects of aprepitant in the viral tropism and envelope sequence of the main HIV-1 population of the participants.
To assess viral drug susceptibility in conjunction with baseline coreceptor tropism phenotype and changes in coreceptor phenotype after the exposure to aprepitant.
To evaluate aprepitant effects on fasting plasma glucose, insulin, HDL, free fatty acids, and triglyceride concentrations after 14 days of treatment.
To provide preliminary description of any change from baseline in sleep quality, anxious mood, depressed mood and neurocognitive measures after 2 weeks of aprepitant therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aprepitant | Active comparator | Drug: AprepitantAprepitant (Emend®) 375 mg daily for 14 days |
| Placebo | Placebo comparator | Drug: Aprepitant placeboAprepitant (Emend®) placebo for 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- HIV-1 infection, as documented by a rapid HIV test or any FDA-Approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test kit and confirmed by Western blot at any time prior to study entry.
- CD4+ cell count >= 350/mm3 obtained within 90 days prior to study entry
- Plasma HIV-1 RNA of >=2,000 copies/mL as measured by any standard assay and performed within 90 days prior to study entry.
- CCR5 tropic virus exclusively as determined by the Monogram tropism assay (PhenoSense Entry™) to be performed within 90 days of study entry.
- Laboratory values obtained within 30 days prior to study entry, as follows:
Key exclusion criteria (15 listed)
- Receipt of antiretroviral treatment within the 16 weeks prior to study entry or intent to initiate antiretroviral therapy within 60 days after entry.
- Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
- Pregnancy within 90 days prior to study entry.
- Breast-feeding.
- Use of drugs that are inhibitors or inducers of metabolism by the cytochrome P450 CYP3A4 or CYP2C9 (such as warfarin and phenytoin) within 7 days of study entry.
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 |
|---|---|---|
| AprepitantAprepitant (Emend®) 375 mg daily for 14 days | Drug | Aprepitant |
| Aprepitant placeboAprepitant(Emend®) placebo for 14 days | Drug | Placebo |
Primary outcome
Virologic: Change in log10 HIV-1 RNA from baseline to Day 14
Time frame: 14 days
For the purposes of assessing the primary analysis of efficacy of aprepitant in reducing viral load we will be assessing the difference between the log10 viral load at baseline and at 4 weeks, and constructing a 95% confidence interval around this mean difference within each dose group.
Safety: Incidence of Grade 2, 3, and 4 adverse events
Time frame: 42 days
The frequency of grade 2,3 and 4 adverse events for the duration of the study will be measured to assess the safety of the compund in this population. Exact binomial confidence intervals will be calculated around the event rates for any individual adverse events that occur and for the overall rate of adverse events within each body system. For each patient the highest grade occurring adverse event within each body system will be assessed. Tables for adverse events by body system and severity of adverse event will be constructed.
3 secondary outcomes
Pharmacokinetic
Time frame: 14 days
Immunologic
Time frame: 14 days
Neurologic
Time frame: 14 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 3 Jun 2016.
- Background: PubMed 11274418Lai JP, Ho WZ, Zhan GX, Yi Y, Collman RG, Douglas SD. Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3970-5. doi: 10.1073/pnas.071052298.
- Background: PubMed 16675550Lai JP, Ho WZ, Kilpatrick LE, Wang X, Tuluc F, Korchak HM, Douglas SD. Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7771-6. doi: 10.1073/pnas.0602563103. Epub 2006 May 4.
- Background: PubMed 12766696Ho WZ, Evans DL, Douglas SD. Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology. CNS Spectr. 2002 Dec;7(12):867-874. doi: 10.1017/s1092852900022483.
- Background: PubMed 11919172Ho WZ, Lai JP, Li Y, Douglas SD. HIV enhances substance P expression in human immune cells. FASEB J. 2002 Apr;16(6):616-8. doi: 10.1096/fj.01-0655fje.
- Background: PubMed 11730941Li Y, Douglas SD, Song L, Sun S, Ho WZ. Substance P enhances HIV-1 replication in latently infected human immune cells. J Neuroimmunol. 2001 Dec 3;121(1-2):67-75. doi: 10.1016/s0165-5728(01)00439-8.
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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 19 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 3 Jun 2016. 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. Some participants in this study may receive a placebo. 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?
Virologic: Change in log10 HIV-1 RNA from baseline to Day 14 (time frame: 14 days). 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 NCT01300988, which also lists 5 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 3 Jun 2016.