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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Virologic: Change in log10 HIV-1 RNA from baseline to Day 14
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
Aprepitant
Aprepitant (Emend®) 375 mg daily for 14 days
干预措施: Aprepitant (Drug)
Placebo
Aprepitant (Emend®) placebo for 14 days
干预措施: Aprepitant placebo (Drug)
结局指标
主要结局
Virologic: Change in log10 HIV-1 RNA from baseline to Day 14
时间窗: 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
时间窗: 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.
次要结局
- Pharmacokinetic(14 days)
- Immunologic(14 days)
- Neurologic(14 days)