The Pharmacokinetics of Extended Duration High-Dose Cefixime Co-administered With Azithromycin for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Peak cefixime level (Cmax)
研究概览
简要总结
This is a PK study of a multi-dose oral cefixime regimen (three 800 mg doses given on a q 8-hour schedule) alone and also co administered with a single 1000 mg oral dose of azithromycin, both within a 24-hour period, in order to achieve total serum cefixime levels of mcg/mL for at least 20 hours. This will determine the tolerability of the regimen and whether there are significant changes in cefixime PK after co-administration. The primary pharmacokinetic objectives are: to determine if a cefixime dosing regimen of three 800 mg doses given alone, on a q 8-hour schedule achieves a total serum cefixime level that exceeds 2.0 mcg/mL for at least 20 hours; to determine if a cefixime dosing regimen of three 800 mg doses given on a q 8 hour schedule co-administered with a single 1000 mg of azithromycin, achieves a total serum cefixime level that exceeds 2.0 mcg/mL for at least 20 hours; and to evaluate whether a single 1000 mg dose of azithromycin alters the PK of a three dose regimen of 800
详细描述
This is a PK study of a multi-dose oral cefixime regimen (three 800 mg doses given on a q 8-hour schedule) alone and also co administered with a single 1000 mg oral dose of azithromycin, both within a 24-hour period, in order to achieve total serum cefixime levels of mcg/mL for at least 20 hours. This will determine the tolerability of the regimen and whether there are significant changes in cefixime PK after co-administration. The primary pharmacokinetic objectives are: to determine if a cefixime dosing regimen of three 800 mg doses given alone, on a q 8-hour schedule achieves a total serum cefixime level that exceeds 2.0 mcg/mL for at least 20 hours; to determine if a cefixime dosing regimen of three 800 mg doses given on a q 8 hour schedule co-administered with a single 1000 mg of azithromycin, achieves a total serum cefixime level that exceeds 2.0 mcg/mL for at least 20 hours; and to evaluate whether a single 1000 mg dose of azithromycin alters the PK of a three dose regimen of 800 mg cefixime given on a q 8-hour schedule. The primary safety objectives are to assess the safety and tolerability of a treatment regimen that includes three doses of 800 mg cefixime; to assess the safety and tolerability of a treatment regimen that includes three doses of 800 mg cefixime co-administered with a single 1000 mg dose of azithromycin. The study will take place for 10 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects between 18 and 45 years, inclusive
- •Ability to understand the consent process and procedures
- •Informed consent obtained and signed prior to initiation of any study procedures
- •Subjects agree to be available for all study visits
- •Negative breathalyzer for alcohol
- •Agreement by female subjects with reproductive potential to use an adequate method of contraception during the study and for 30 days after last study drug administration. Female subjects must agree to the use of TWO reliable methods of contraception while receiving study drug and for 30 days after last study drug administration if sexually active, which can include: condoms, spermicidal gel, diaphragm, hormonal or non-hormonal intrauterine device, surgical sterilization, oral contraceptive pill (OCP), and depot progesterone injections.
排除标准
- •Subjects who take any prescription medication on a regular basis (except OCPs), including but not limited to, anti-psychotics, anti-depressants, anti-epileptics, cardiac medications, and antihypertensives.
- •Subjects who take any OTC drugs or herbal remedies on a regular basis, especially those that have been associated with a risk of QT prolongation such as antiemetics (ondansetron, granisetron, dolasetron, hydroxyzine), antihistamines (terfenadine, astemizole, hydroxyzine, diphenhydramine), GI stimulants (cisapride, domperidone, metoclopramide), and homeopathic agents (cinchona, licorice extract- glycyrrhizin).
- •Hypertension with confirmed systolic blood pressure >140 mmHg or confirmed diastolic blood pressure > 90 mmHg, measured after 10 to 15 minutes of rest
- •Morbid obesity (BMI >/= 35 kg/m^2)
- •Current diagnosis of pulmonary disease
- •History or current diagnosis of diabetes
- •Autoimmune disorders, such as lupus, Wegener's, rheumatoid arthritis
- •History of malignancy except low-grade skin cancer, (i.e., basal cell carcinoma thought to be cured)
- •Known diagnosis of prolonged QT interval, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure
- •History of alcohol abuse
- •History of seizure disorder
- •History of renal disease
- •Chronic renal, hepatic, or pulmonary disease or other condition that could interfere with the absorption of the study drug or predispose to adverse GI events (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, irritable bowel syndrome, inflammatory bowel disease)
- •Positive serology results for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies
- •Subjects who have taken any prescription drugs in the previous 14 days or within five half-lives before dosing
- •Ingestion of OTC medications or herbal supplements within seven days of dosing
- •Positive urine drug screen for marijuana, cocaine, amphetamines, opiates, phencyclidine, barbiturates, or benzodiazepines
- •History of allergic reaction or intolerance to cephalosporins
- •History of allergic reaction to penicillin (all stages)
- •History of allergic reaction to azithromycin, erythromycin, or any macrolide or ketolide antibiotic
- •History of jaundice or hepatic dysfunction associated with prior use of azithromycin
- •Males with a QTcF > 430ms or Females with a QTcF >450ms (Fridericia's correction) on screening
- •Positive pregnancy test; pregnant or nursing women
- •Screening laboratory tests > Grade 1 as defined by Appendix B
- •Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety.
研究组 & 干预措施
Cefixime/Azithromycin
Eight participants will receive three oral doses of 800 mg cefixime (q 8 hours) on Day 1, followed by three oral doses of 800 mg cefixime (q 8 hours)+ one oral dose of 1000 mg azithromycin (with first dose of cefixime) on day 10
干预措施: Azithromycin (Drug)
Cefixime/Azithromycin
Eight participants will receive three oral doses of 800 mg cefixime (q 8 hours) on Day 1, followed by three oral doses of 800 mg cefixime (q 8 hours)+ one oral dose of 1000 mg azithromycin (with first dose of cefixime) on day 10
干预措施: Cefixime (Drug)
结局指标
主要结局
Peak cefixime level (Cmax)
时间窗: Day 1,2,3,10,11,12 and at early termination
Elimination rate (lambda z)
时间窗: Day 1,2,3,10,11,12 and at early termination
Individual plasma cefixime levels will be used to generate PK curves of cefixime levels versus time
时间窗: Day 1,2,3,10,11,12 and at early termination
AUC from 0 to infinity [AUC0-infinity]
时间窗: Day 1,2,3,10,11,12 and at early termination
Averaged composite plasma cefixime levels will be used to generate PK curves of cefixime levels versus time
时间窗: Day 1,2,3,10,11,12 and at early termination
Elimination half-life (t1/2)
时间窗: Day 1,2,3,10,11,12 and at early termination
Time that cefixime levels exceed four times the MIC of 0.5 mcg/mL (i.e., a plasma level of 2.0 mcg/mL)
时间窗: Day 1,2,3,10,11,12 and at early termination
Time to peak drug level (Tmax)
时间窗: Day 1,2,3,10,11,12 and at early termination
Safety blood test results
时间窗: Day: -28,-1, 2, 3, 9, 11, 12, 17 and at early termination
Safety urinanalysis results
时间窗: Day: -28, -1, 2, 3, 9, 11, 12, 17 and at early termination
Subject reported AEs
时间窗: Day: 1, 2, 3, 9, 10, 11, 12, 17 and at early termination
Subject reported serious adverse events (SAEs)
时间窗: Day: 1, 2, 3, 9, 10, 11, 12, 17 and at early termination
Targeted clinical evaluations
时间窗: Day: -1,1, 2, 3, 9, 10, 11, 12, 17 and at early termination
Total area under the curve (AUC from 0 hours to the time of next dosing [AUC0-t])
时间窗: Day 1,2,3,10,11,12 and at early termination
Total plasma concentrations of cefixime
时间窗: Day 1,2,3,10,11,12 and at early termination
次要结局
未报告次要终点