A Phase I, Open-Label Study to Determine the Effect of Repeat Dosing of Trametinib on the Pharmacokinetics and Safety of a Combined Oral Contraceptive (Norethindrone Plus Ethinyl Estradiol) and to Characterize the Pharmacokinetics of Trametinib's Metabolite M5 in Female Subjects With Solid Tumors

This is a Phase I, open-label, non-randomized, sequential, two-period, repeat-dose study to evaluate the effect of trametinib 2 milligram (mg) once daily on the repeat-dose pharmacokinetic (PK) of an oral contraceptive (OC) containing norethindrone (NE) and ethinyl estradiol (EE) (ORTHO-NOVUM® tablets: 1 mg NE + 0.035 mg EE) in female subjects with solid tumors.
The study will determine PK interaction between trametinib and the components of combination oral contraceptives that would compromise the effectiveness of the contraceptives.
The study will also evaluate the repeat dose PK of trametinib and its metabolite M5 using a validated assay.
The study will enroll approximately 24 subjects. Each subject will participate in the study for approximately up to 13 to 15 weeks which will consist of a 30 day screening period, followed by 2 treatment periods (Period 1: 28 days and Period 2: ranging from 12 days to up to 21 days), and a transition visit or post-treatment follow-up visit. In Period 1, subjects will take one active tablet from the ORTHO-NOVUM® tablet 1/35 dial-pack once daily at approximately the same time each day for 21 days (Days 1 through 21), followed by one inert (referred to as placebo) tablet once daily at approximately the same time each day for 7 days (Days 22 through 28). In addition, subjects will take trametinib 2 mg (1 tablet) once daily at approximately the same time each day for a total of 17 days (Days 12 through 28). In Period 2, subjects will take one active tablet from the ORTHO-NOVUM® tablet 1/35 dial-pack once daily at approximately the same time each day for 11 days (Days 1 through 11). In addition, subjects will continue taking trametinib 2 mg (1 tablet) once daily at approximately the same time each day for 11 days (Days 1 through 11). ORTHO-NOVUM® is a registered trademark of Ortho Pharmaceutical Corporation.

开始日期2016-02-01

申办/合作机构

GSK Plc

NCT01044498 / Completed临床3期

An Open-label, Multi-center, One Sequence Cross-over Drug Interaction Study to Investigate the Effect of Tocilizumab (TCZ, RO4877533) on the Pharmacokinetics and Pharmacodynamics of an Oral Contraceptive (OC) in Female Patients With Active Rheumatoid Arthritis (RA)

This open-label, randomized, cross-over study evaluated the effect of tocilizumab (TCZ) on the pharmacokinetics and pharmacodynamics of a common oral contraceptive (OC) in female patients with active rheumatoid arthritis (RA) and in healthy female volunteers of child bearing age. The RA patients received OC in combination with TCZ, whereas the healthy volunteers received OC only. The RA patients received OC in 3 cycles of 21 days each; TCZ 8 mg/kg was administered once as an intravenous infusion on the first day of Cycle 2. The healthy volunteers received OC for only one 21-day cycle.

开始日期2009-12-01

申办/合作机构

Hoffmann-La Roche, Inc.

NCT00972439 / CompletedN/AIIT

Evaluating the Effect of Oral Contraceptive Progestin Dose on Breast Epithelial Cell Proliferation

The purpose of this research study is to gain a better understanding of the changes that may occur in the breast when a woman uses an oral contraceptive (birth control pill). Some research indicates that women who use birth control pills with lower amounts of progestin (a hormone in the birth control pill) may have lower breast cell growth than women who use birth control pills with a higher amount of progestin; this research will examine that in detail.

开始日期2007-08-01

申办/合作机构

University of Southern California

[+1]

100 项与美雌醇/炔诺酮相关的临床结果

登录后查看更多信息

100 项与美雌醇/炔诺酮相关的转化医学

登录后查看更多信息

100 项与美雌醇/炔诺酮相关的专利（医药）

登录后查看更多信息

项与美雌醇/炔诺酮相关的文献（医药）

2013-12-01·British Journal of Ophthalmology2区 · 医学

Angiographically documented transient monocular blindness: retinal migraine?

2区 · 医学

Article

作者: Kosmorsky, Gregory S

A 30-year-old African–American woman began to experience transient visual loss in the right eye 3 days before presentation on 15 February 1988. These episodes lasted from one to several minutes and consisted of flashing lights, grey-outs and episodes of no light perception (NLP) vision relegated solely to her right eye. She did not experience headache, diplopia or any other focal neurologic phenomena. A total of 8–10 of these episodes had been experienced in the previous 3 days. Concomitantly, she had experienced anorexia and abdominal tenderness without fever, chills or other constitutional symptoms. She had no significant past medical or ophthalmologic history. She did experience migraines with her menses in the preceding 5 years. These episodes usually occurred just preceding or during menses, and were throbbing and associated with nausea without vomiting. The episodes were usually unilateral and mainly on the right side. These episodes could last for several hours or up to several days during the menstrual cycle. She did not experience migrainous aura. Her only medication was Ortho-Novum. She had presented to the retina clinic for evaluation while asymptomatic, and suddenly experienced painless vision loss to the NLP level in the right eye. Being immediately whisked to the neurophthalmology clinic, a 4+afferent pupillary defect was detected in the affected eye and the NLP vision corroborated. Examination of the fundus revealed obvious venous boxcarring indicative of a lack of arterial perfusion. The optic disc appeared pale in comparison with the disc on the left side. No definitive change in the calibre of the blood vessels could be ascertained (figure 1). With firm digital pressure, no arterial or venous pulsations could be induced indicating severe lack of arterial flow. A fluorescein angiogram revealed an almost immediate blush of the choroid, while the central retinal arterial circulation was grossly delayed (figure 2). Her visual acuity …

2011-09-01·The Journal of Clinical Pharmacology3区 · 医学

Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, Does Not Affect the Pharmacokinetics of Ethinyl Estradiol or Norethindrone in Healthy Female Subjects

3区 · 医学

Article

作者: Elizabeth Migoya ; Arthur Bergman ; Kenneth C. Lasseter ; Jutta Miller ; Patrick Larson ; Amy O. Johnson-Levonas ; John A. Wagner

Sitagliptin is a dipeptidyl peptidase-IV (DPP-4) inhibitor used for the treatment of patients with type 2 diabetes mellitus. This randomized, placebo-controlled, 2-period, crossover study evaluated the effect of sitagliptin on the pharmacokinetics of 17 α-ethinyl estradiol (EE(2)) and norethindrone (NET) in healthy female subjects who were receiving oral contraceptives for >3 months prior to enrollment. A total of 18 subjects with normal menstrual cycles received the oral contraceptive pill ORTHO-NOVUM(®) 7/7/7 on days 1 to 28 for 2 successive cycles, and on days 1 to 21 were randomly assigned to receive sitagliptin 200 mg/day (2 × 100 mg tablets) or placebo using a computer-generated allocation schedule. Blood samples for determination of plasma EE(2) and NET concentrations were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdose on day 20 or 21 of each treatment period. The GMRs (90% confidence interval [CI]) for the AUC(0-24 hr) of EE(2) and NET were 0.99 (0.93, 1.06) and 1.03 (0.97, 1.09), respectively, and for C(max) were 0.97 (0.86, 1.10) and 0.98 (0.89, 1.07), respectively. The coadministration of sitagliptin 200 mg/day with an oral contraceptive for 21 days did not lead to clinically meaningful alterations in the pharmacokinetics of EE(2) and NET.

2008-06-01·Psychiatry and Clinical Neurosciences

Atypical depression as a premonitory symptom of migraine managed by an oral contraceptive

Letter

作者: Tomomichi Endo ; Satoshi Kawamura ; Akio Sakai ; Masaki Maruta

Depression and headaches are frequently associated comorbid disorders. In previous reports psychiatrists have tended to regard headaches as an accompanying symptom of depression while neurologists have tended to have the opposite opinion. The following case report characterizes migraine as a prime cause of major depression. A 27-year-old woman presented because of a self-poisoning attempt with 12 mg of alprazolam. She had been suffering from major depression and sporadic headaches from the age of 24. After onset of the symptoms she had often injured herself by cutting her arm and attempted to suicide by self-poisoning. A variety of antidepressants had failed to improve her symptoms and she had been diagnosed as having borderline personality disorder comorbid with major depression. A medical interview at her first visit revealed that her major depressive episode had been predominantly characterized by atypical features in DSM-IV such as overeating hypersomnia leaden paralysis interpersonal rejection sensitivity and mood reactivity. She had also suffered persistent aura and premonitory symptoms of migraine such as scintillating scotomas photopsia and phonophobia.1 Lomerizine a calcium channel antagonist was first administered at 10 mg/day for treatment of the migraine in combination with valproic acid at 600 mg/day. This medication led to prompt resolution of her self-injury and suicidal behaviors but depressive mood with a series of migraine attacks paralleling each menstrual period persisted. Therefore additionally the patient was prescribed Ortho-Novum®7/7/7 an oral contraceptive containing ethinyl estradiol and norethindrone to prevent ovulation. With this medication all the symptoms immediately disappeared. Lomerizine and valproic acid were gradually withdrawn and no recurrence has been noted for over 1 year. Depression is one of the common premonitory symptoms of migraine and a first-line treatment strategy for migraine showed some degree of clinical effectiveness on the depressive episode in the present case.12 Accordingly it was considered that the patients major depression was also a premonitory symptom of migraine. Ovarian hormones can alter neurotransmitter system theorized to play an important role in the pathogenesis of migraine.3 Although hormonal treatment of migraine is not a first-line strategy due to an increased risk of ischemic stroke oral contraceptives can have a broad effect on the character and frequency of migraine.45 We suggest that clinicians should check for the complication of migraine in depressive patients. Depressive patients with migraine might show a preferential response to management of migraine rather than medication with common antidepressants. In female patients it is also prudent to be aware of any symptomatic relevance to the menstrual cycle and that oral contraceptives have the potential to treat such problems. (full-text)

项与美雌醇/炔诺酮相关的新闻（医药）

2023-09-04

·药时代

超越曲妥珠单抗！再鼎这款HER2单抗国内获批上市！

2023年9月1日，根据中国国家药监局（NMPA）官网公示，再鼎医药的马吉妥昔单抗（margetuximab）注射液已在中国获批上市，此次获批的适应症为联合化疗治疗已经接受过至少两种抗HER2治疗方案的复发、转移性HER2阳性乳腺癌成人患者。乳腺癌是女性高发的癌症，乳腺癌患者中，多存在肿瘤细胞的人类表皮生长因子受体2（HER2）存在过表达现象，HER2的过表达可导致癌细胞的加速生长，约25%的转移性HER2阳性乳腺癌患者会发生脑转移，对患者的威胁较大。马吉妥昔单抗是一种作用于HER2的Fc优化型单克隆抗体，可减少HER2细胞外域的脱落，并增强抗体依赖性细胞介导的细胞毒性作用（ADCC）。该药于2018年11月由再鼎医药从MacroGenics公司引进。在一项名为SOPHIA（NCT02492711）的随机、开放标签的3期临床研究中，评估了曲妥珠单抗联合化疗与马吉妥昔单抗联合化疗对该类型乳腺癌患者的治疗效果。该研究共纳入受试者536名，按1：1的比例随机分配，曲妥珠单抗（15mg/kg或6mg/kg）和马吉妥昔单抗15mg/kg或6mg/kg）均配合化疗药物每三周进行一次静脉注射。结果显示，相较于曲妥珠单抗，马吉妥昔单抗组获得了更好的中位无进展生存期（PFS）（5.8个月 VS 4.9个月），马吉妥昔单抗联合化疗组显降低了患者的疾病进展或死亡的风险，根据报道，马吉妥昔单抗是唯一在曲妥珠单抗对比研究中表现出可以延长PFS的抗HER2治疗方法。安全性方面，大多数报告为2级以下，1.5％的患者发生3级IRR。在随后的2021年和2022年，再鼎医药又先后宣布了马吉妥昔单抗在大中华区用于治疗晚期HER2阳性乳腺癌的桥接研究达到主要研究终点和相关临床数据。结果与SOPHIA类似，马吉妥昔单抗组同样获得了更好的PFS（5.8个月 VS 4.9个月），证明了马吉妥昔单抗在中国人群中的有效性。总之，既往治疗HER2阳性晚期乳腺癌中，标准治疗手段为化疗药物+曲妥珠单抗/拉帕提尼。不过，近些年来曲妥珠单抗的销售额持续下跌，仅2018年到2022年间，曲妥珠单抗全球销售额由69.82亿瑞士法郎降至21.42亿瑞士法郎，整整下降了69.32%，罗氏也为此做出了许多努力，如开发出了曲妥珠单抗的ADC版本“赫赛莱”等。不过，究其下降的主要原因，还是如马吉妥昔单抗等更优秀的“后浪”上岸，开始抢夺市场。作为乳腺癌领域的基石疗法，曲妥珠单抗很有可能在未来的一段时间仍占据着该领域的“半壁江山”，但“后生可畏”，我们也期待马吉妥昔单抗在中国市场的表现！参考资料：1.再鼎官网2. 国家药监局官网3.其他公开资料封面图来源：123rf8月，23家药企宣布裁员！点击这里，与药时代一起快乐学习！

上市批准临床3期抗体药物偶联物临床结果

100 项与美雌醇/炔诺酮相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	美雌醇/炔诺酮	G03FA01 G03FB05	-

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
月经紊乱	日本	ASKA Pharmaceutical Co., Ltd.	1967-02-15

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00972439 (CTgov)	N/A	避孕	33	Oral Contraceptive: Ortho-Novum® 1/35 (Ortho-Novum® 1/35)	鬱蓋膚鑰窪構膚糧網遞(鹹憲網壓獵壓鹽簾積夢) = 艱夢壓淵構鏇範夢壓顧鹽鏇網夢餘製餘窪蓋廠 (憲廠蓋選鑰壓選遞選壓, 鏇簾鏇繭糧糧鹽衊顧製 ~ 餘襯繭構鹽簾積觸窪繭) 更多	-	2018-02-23
				Oral Contraceptive: Ovcon Fe® (Ovcon Fe®)	鬱蓋膚鑰窪構膚糧網遞(鹹憲網壓獵壓鹽簾積夢) = 醖膚顧網艱築鑰選憲鏇鹽鏇網夢餘製餘窪蓋廠 (憲廠蓋選鑰壓選遞選壓, 糧鹹繭簾網鹽獵壓鬱淵 ~ 顧餘淵齋遞顧選窪遞淵) 更多
NCT01044498 (CTgov)	临床3期	类风湿关节炎	46	tocilizumab+Ortho-Novum® 1/35 (Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1))	衊窪積蓋範蓋鏇簾醖積(窪淵積憲淵範齋窪餘艱) = 廠築鏇鬱襯鹽醖壓選蓋鏇鏇廠醖簾衊齋憲積網 (壓壓淵選齋壓製構構鏇, 鏇膚衊顧鬱襯壓網鏇蓋 ~ 製衊構獵鹹蓋繭範積積) 更多	-	2013-03-12
				Ortho-Novum® 1/35 (Ortho-Novum® 1/35 (Group 2))	衊窪積蓋範蓋鏇簾醖積(窪淵積憲淵範齋窪餘艱) = 襯製簾鹽積鑰鏇壓廠鹹鏇鏇廠醖簾衊齋憲積網 (壓壓淵選齋壓製構構鏇, 製網網糧顧鏇願憲鏇壓 ~ 積壓構選淵襯鑰構齋積) 更多