An Open-label, Multi Centre Drug-drug Interaction Trial to Investigate the Effects of Tralokinumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Subjects With Moderate-to-severe Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- LEO Pharma
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Ratio of the Cmax at Week 15 (after multiple doses of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates
研究概览
简要总结
The purpose of this trial is to investigate if tralokinumab changes the metabolism of selected CYP substrates in adults with moderate-to-severe AD after:
- 14 weeks of treatment with tralokinumab
- a single dose of tralokinumab
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 and above.
- •Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD.
- •History of AD for ≥1 year.
- •Subjects who have a recent history of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable.
- •AD involvement of ≥10% body surface area at screening and baseline.
- •Stable dose of emollient twice daily (or more, as needed) for at least 14 days before baseline.
- •Willingness to abstain from consumption of any 1 or more of the following items in the periods specified:
- •±7 days within each cocktail dosing visit: foods/beverages that affect the CYP system:
- •Grapefruit or grapefruit juice, Seville oranges or orange juice, starfruit, pomegranate and cranberry juices, red wine, red grape extract.
- •Cruciferous vegetables (for example broccoli).
- •Chargrilled meat.
- •±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.
排除标准
- •Administration, within 14 days or 5 half-lives (whichever is longer) prior to Day -7, of any medication that is a known inducer or inhibitor of 1 or more of the following CYP enzymes: CYP3A, CYP2C19, CYP2C9, CYD2D6, and CYP1A
- •Subjects who are poor metabolisers of CYP2C9, CYP2C19, or CYP2D6, based on genotyping.
- •Any contraindication to 1 or more of the following drugs, according to the applicable labelling: caffeine, warfarin, omeprazole, metoprolol, or midazolam.
- •Consumption of any 1 or more of the following items in the periods specified:
- •±7 days within each cocktail dosing visit: foods/beverages that affect the CYP system:
- •Grapefruit or grapefruit juice, Seville oranges or orange juice, starfruit, pomegranate and cranberry juices, red wine, red grape extract.
- •Cruciferous vegetables (for example broccoli).
- •Chargrilled meat.
- •±48 hours within each cocktail dosing visit: caffeinated beverages and foods/drugs that contain caffeine.
- •Nausea or diarrhoea 1 week prior to Day -
- •Active dermatologic conditions that may confound the diagnosis of AD.
- •Use of tanning beds or phototherapy within 5 weeks prior to Day -
- •Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 3 weeks prior to Day -
- •Treatment with topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors within 1 week prior to Day -
- •Receipt of any marketed biological therapy or investigational biologic agent (including immunoglobulin, anti-IgE, or dupilumab):
- •Any cell-depleting agents, including but not limited to rituximab: within 6 months prior to Day -7, or until lymphocyte count returns to normal, whichever is longer.
- •Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to Day -
- •Active skin infection within 1 week prior to Day -
- •Clinically significant infection within 4 weeks prior to Day -
- •A helminth parasitic infection within 6 months prior to the date informed consent is obtained.
- •Tuberculosis requiring treatment within 12 months prior to screening.
- •Known primary immunodeficiency disorder.
研究组 & 干预措施
All subjects
Tralokinumab - investigational medicinal product:
Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
Week 2 to Week 14: SC injection of tralokinumab maintenance dose.
CYP substrates - non-investigational medicinal products:
Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
干预措施: Tralokinumab (Drug)
All subjects
Tralokinumab - investigational medicinal product:
Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
Week 2 to Week 14: SC injection of tralokinumab maintenance dose.
CYP substrates - non-investigational medicinal products:
Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
干预措施: Caffeine (Drug)
All subjects
Tralokinumab - investigational medicinal product:
Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
Week 2 to Week 14: SC injection of tralokinumab maintenance dose.
CYP substrates - non-investigational medicinal products:
Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
干预措施: Warfarin (Drug)
All subjects
Tralokinumab - investigational medicinal product:
Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
Week 2 to Week 14: SC injection of tralokinumab maintenance dose.
CYP substrates - non-investigational medicinal products:
Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
干预措施: Omeprazole (Drug)
All subjects
Tralokinumab - investigational medicinal product:
Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
Week 2 to Week 14: SC injection of tralokinumab maintenance dose.
CYP substrates - non-investigational medicinal products:
Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
干预措施: Metoprolol (Drug)
All subjects
Tralokinumab - investigational medicinal product:
Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
Week 2 to Week 14: SC injection of tralokinumab maintenance dose.
CYP substrates - non-investigational medicinal products:
Week -1, Week 1, and Week 15: oral administration of caffeine 100 mg, warfarin sodium 5 mg x2, omeprazole 20 mg, metoprolol tartrate 100 mg, and midazolam hydrochloride 2 mg.
干预措施: Midazolam Hydrochloride (Drug)
结局指标
主要结局
Ratio of the Cmax at Week 15 (after multiple doses of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates
时间窗: Day -7 and Week 15
Cmax = maximum observed plasma concentration
Ratio of the AUC-last at Week 15 (after multiple doses of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates
时间窗: Day -7 and Week 15
AUC-last = area under the plasma concentration curve from time 0 to the last quantifiable observation
次要结局
- Number of adverse events(From Day 1 up to Week 30)
- Ratio of the Cmax on Day 8 (after a single dose of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates(Day -7 and Day 8)
- Ratio of the AUC-inf on Day 8 (after a single dose of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates(Day -7 and Day 8)
- Ratio of the AUC-last on Day 8 (after a single dose of tralokinumab) to that on Day -7 (at baseline) for each of the 5 substrates(Day -7 and Day 8)
- Presence of anti-drug antibodies (yes/no)(From Day 1 up to Week 30)