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.

Start Date01 Feb 2016

Sponsor / Collaborator

GSK Plc

NCT01044498 / CompletedPhase 3

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.

Start Date01 Dec 2009

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

NCT00972439 / CompletedNot ApplicableIIT

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.

Start Date01 Aug 2007

Sponsor / Collaborator

University of Southern California

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100 Clinical Results associated with Mestranol/Norethindrone

100 Translational Medicine associated with Mestranol/Norethindrone

100 Patents (Medical) associated with Mestranol/Norethindrone

Literatures (Medical) associated with Mestranol/Norethindrone

01 Dec 2013·British Journal of OphthalmologyQ2 · MEDICINE

Angiographically documented transient monocular blindness: retinal migraine?

Q2 · MEDICINE

Article

Author: 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 …

01 Sep 2011·The Journal of Clinical PharmacologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

01 Jun 2008·Psychiatry and Clinical Neurosciences

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

Letter

Author: 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)

100 Deals associated with Mestranol/Norethindrone

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KEGG	Wiki	ATC	Drug Bank
-	Mestranol/Norethindrone	G03FA01 G03FB05	-

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Indication	Country/Location	Organization	Date
Menstruation Disturbances	JP	ASKA Pharmaceutical Co., Ltd.	15 Feb 1967

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00972439 (CTgov)	Not Applicable	Contraception	33	Oral Contraceptive: Ortho-Novum® 1/35 (Ortho-Novum® 1/35)	nzyqiganhu(npynglvfon) = qpiptuxfpi yxzkqbwgrj (nadpukgblk, aefituujyf - xskcqdpmwt) View more	-	23 Feb 2018
				Oral Contraceptive: Ovcon Fe® (Ovcon Fe®)	nzyqiganhu(npynglvfon) = vadiqtnbbn yxzkqbwgrj (nadpukgblk, gxvwqnfhzn - dszyhiqoln) View more
NCT01044498 (CTgov)	Phase 3	Rheumatoid Arthritis	46	tocilizumab+Ortho-Novum® 1/35 (Tocilizumab 8 mg/kg + Ortho-Novum® 1/35 (Group 1))	lyjcgngjdu(kjodtoahki) = hgvdqxufhe ommxqpzobm (mauxzhkuyq, mtbknmagew - siwkrggrtn) View more	-	12 Mar 2013
				Ortho-Novum® 1/35 (Ortho-Novum® 1/35 (Group 2))	lyjcgngjdu(kjodtoahki) = ocevahgejm ommxqpzobm (mauxzhkuyq, okxgcjlgnp - tlarhlepha) View more

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