A Pharmacokinetic and Safety Study of Procaine HCl in HIV-1 Infected Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Mean viral load reduction (log10) over 8 weeks
研究概览
简要总结
This a Phase I/II non-randomized, open-label clinical study of 8 weeks duration using SP01A in HIV positive patients on a stable antiretroviral regimen. Dose response and safety associated with oral administration of four doses (200 mg, 400 mg, 600 mg, and 800 mg daily) of SP01A will be studied in a total of 24 study subjects. In addition, six HIV-negative subjects will be recruited as a control for cortisol secretion only and will not receive study medication.
详细描述
STUDY PLAN: DESCRIPTION This investigation will be a non-randomized, open-label study of four doses of SP01A in 24 individuals infected with HIV who are being treated with triple combination antiretroviral therapy. Additionally, a group of six HIV-negative subjects (group E) is being recruited as a control for cortisol secretion. This group will not receive study medication nor will they be evaluated for dose response or safety parameters.
DISCUSSION OF STUDY DESIGN, INCLUDING CONTROL GROUP Patients will receive the following doses of SP01A and will be divided into a low dose and high dose group for further analyses. There will be two segments within the low dose group. Group A will receive 200 mg of SP01A once per day. Group B will be administered 200 mg of SP01A twice daily. Similarly, there will be two segments in the high dose group. Group C will be treated with 200 mg of SP01A three times per day, while Group D will be administered 400 mg of SP01A twice daily.
A fifth group will also be introduced. This group, Group E, will serve as a control group and not receive any treatment.
The study will be conducted at a single investigative center (AIDS ReSearch Alliance, West Hollywood, CA). Six subjects with a diagnosis of HIV who are also receiving triple combination antiretroviral therapy and have been so doing for a minimum of 2 months are planned per group. Patients will be admitted to an in-patient facility for 72 hours. After an initial night to acclimate the patients to the facility, a 24-hour measurement of cortisol secretion in blood and urine will be conducted. After this is complete, patients will receive an initial single dose of SP01A orally. (200 mg SP-01A for group A, 400 mg for group B, 600 mg for group C, and 800 mg for group D). Blood and urine samples will also be collected for 24 hours to further evaluate the safety of the study medication. Patients will then be discharged from the facility.
After a 4-day washout, patients will return to the facility to start an 8-week dose-response study, sequentially using the four doses that will now be divided (200 mg daily for group A, 200 mg twice a day for group B, 200 mg three times per day for group C, and 400 mg twice daily for group D).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Eighteen years of age or older (male or female).
- •If female, agreed to use suitable contraception to prevent pregnancy.
- •HIV positive as confirmed by viral load using nucleic acid sequence based amplification (NASBA), or enzyme-linked immunosorbent assay (ELISA) and Western Blot, for cohort A, B, C, and D. HIV negative by ELISA and Western blot for cohort E.
- •Karnofsky Performance Status score of at least
- •No active opportunistic infection. Prophylaxis for MAl, CMV, Pneumocystis Pneumonia except Bactrim), or herpes was permitted.
- •Current CD4 count >
- •Stable triple therapy antiretroviral regimen (cohorts A, B, C, and D) for the preceding 8 weeks and willing to make no changes in regimen during the study.
- •Not taking any unapproved or experimental treatment for HIV, including antiretrovirals and immune modulators (such as interferons or interleukins).
- •Capable and willing to provide informed consent.
- •Agreed not to take Epoetin during the trial.
- •Baseline laboratory values:
- •Neutrophils > 1000 cells/mm3; Platelets > 75,000 cells/mL; SGOT <3 times upper limit of normal; SGPT <3 times upper limit of normal; Creatinine <2.0 mg/dL.
排除标准
- •Known or suspected allergy to procaine hydrochloride.
- •Patients taking DHEA supplementation or oral ketoconazole (which have anticortisol properties).
- •Patients using sulfonamides (including Septra/Bactrim).
- •Required use of sulfonamides, eg, Septra/Bactrim. (Procaine hydrochloride may inactivate sulfonamides).
- •Patients with glaucoma using anti-cholinesterase inhibitors (Humorsol [demecarium bromide] echothiophate iodide, Floropryl [isoflurophate], Isopto-Eserine [physostigmine salicylate]). Anti-cholinesterase Inhibitors should not be used while on procaine hydrochloride, since procaine itself has some anti-cholinesterase activity.
- •Patients with less than 6 months life expectancy.
- •Patients with adrenal insufficiency (determined by screening ACTH stimulation test).
- •Patients with lymphoma.
- •Patients with active hepatitis (viral or drug induced).
- •Patients with cancer, except peripheral Kaposi's sarcoma.
- •Patients on dialysis.
- •Patients who are pregnant.
- •Female patients of childbearing age who can not use two forms of birth control or abstain from sexual intercourse during the trial.
- •Any medical, psychological, psychiatric, or substance use problem that, in the opinion of the Principal Investigator, interferes with the patient's ability to complete the study.
结局指标
主要结局
Mean viral load reduction (log10) over 8 weeks
Maximal viral load suppression (LDL <50 & 400) over 8 weeks
Cortisol reduction over 8 weeks
次要结局
- Improvement in quality of life indices (Whalen Scale) over 8 weeks