A Phase 1, Open-Label, 2-Arm, Fixed-Sequence Study to Evaluate the Potential Effects of Multiple Doses of Rifampin (CYP3A4 Inducer) and Clarithromycin (CYP3A4 Inhibitor) on the Single Dose Pharmacokinetics of Deflazacort in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
研究概览
简要总结
The primary objective of the study is to determine the potential effects of multiple doses of rifampin and clarithromycin on the single dose pharmacokinetics (PK) of the deflazacort active metabolite (21 desacetyl-DFZ) in healthy adult subjects.
详细描述
This is an open label, parallel 2-arm, 2-period, fixed-sequence study in 58 healthy adult non-tobacco using male and female subjects divided into 2 cohorts, with 29 subjects in each arm of the study (Cohorts A and B).
Cohort A:
On Day 1 of Period 1 a single oral dose of deflazacort (Treatment A) will be administered followed by PK sampling for 24 hours for 21 desacetyl DFZ and, if data permit, deflazacort.
In Period 2, multiple oral doses of rifampin will be administered once daily (QD) for 10 consecutive days with a single oral dose of deflazacort coadministered on Day 10 (Treatment B). Pharmacokinetic sampling for 21-desacetyl-DFZ and, if data permit, deflazacort will be taken for 24 hours following deflazacort dosing on Day 10. Morning urine collection will be used to measure 6β-hydroxycortisol and free cortisol concentrations on Days 1, 4, 8, and 10 to evaluate the level of cytochrome P450 (CYP) enzyme induction.
Cohort B:
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male or female, 18 55 years of age
- •Continuous non smoker who has not used nicotine containing products for at least 3 months
- •Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2
- •For a female of non childbearing potential: must have undergone a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to the first dose of study drug and FSH serum levels consistent with postmenopausal status
- •A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days
- •If male, must agree not to donate sperm from the first dose of study drug until 90 days
排除标准
- •Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
- •History or presence of alcoholism or drug abuse within the past 2 years
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (e.g., steroids or their formulations including lactose)
- •History or presence of:
- •Symptomatic cardiomyopathy at screening
- •Immunosuppression or other contraindications for corticosteroid treatment
- •History of chronic systemic fungal or viral infections
- •Galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption
- •Diabetes mellitus
- •Osteoporosis
- •Myasthenia gravis
- •Idiopathic hypocalcuria
- •Hypothyroidism (TSH clinically significant)
- •Gastrointestinal issues or ulcers
- •Previous corticoids-induced myopathy
- •Ocular herpes simplex
- •Female subjects of childbearing potential
- •Female subjects who are pregnant or lactating
- •Positive urine drug or alcohol results
- •Positive urine cotinine
- •Positive results for HIV, HBsAg or HCV
- •Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg
- •Seated heart rate is lower than 40 bpm or higher than 99 bpm
- •QTc interval is > 430 msec (males) or > 450 msec (females)
- •Has received any live or live-attenuated vaccine within 30 days
- •Has received any immunosuppressive agents, coal tar, and/or radiation therapies within 30 days
- •Has received injectable corticoids in the 12 weeks dose of study drug or any oral form of corticoids in 30 days
- •Estimated creatinine clearance < 80 ml/min
- •Unable to refrain from or anticipates the use of
- •Any drug, including prescription and non prescription medications, as well as herbal remedies known to be significant inhibitors of CYP 3A4 enzymes and/or P gp for 14 days
- •Any drugs known to be significant inducers of CYP 3A4 enzymes and/or P gp, including St. John's Wort, for 28 days
- •Have been on a diet incompatible with the on study diet within 28 days
- •Donation of blood or significant blood loss within 56 days
- •Plasma donation within 7 days
- •Participation in another clinical trial within 28 days
研究组 & 干预措施
Cohort A Deflazacort and Rifampin
Subjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 10, Period 2; cohort A. Subjects will receive once daily dosing of rifampin on Day 1, Period 2 through Day 10, Period 2.
干预措施: Deflazacort and rifampin (Drug)
Cohort B Deflazacort and Clarithromycin
Subjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 4, period 2; cohort B. Subjects will receive twice daily dosing of clarithromycin on Day 1, Period 2 through Day 4, Period 2.
干预措施: Deflazacort and Clarithromycin (Drug)
结局指标
主要结局
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
时间窗: 10 days and 4 days
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
次要结局
- Safety and tolerability of one dose of deflazacort in healthy subjects receiving CYP3A4 inhibitors and inducers as measured by capturing occurrence of adverse events.(10 days and 4 days)