M0001 Effects on Oral Contraceptive Plasma Levels

Study Overview
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Brief Summary
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This is a randomized, open-label, two-way cross-over drug-drug interaction Phase I trial. The objectives of this phase I trial are to investigate in healthy female subjects: the effect of prucalopride on the absorption of ethinylestradiol and norethisterone acetate, the active constituents of several oral contraceptives, after the first dose of prucalopride. the effect of multiple oral dosing of 2 mg prucalopride, for 6 days o.d. (steady state), on the pharmacokinetics of ethinylestradiol and norethisterone acetate. This trial will be conducted in healthy females of child bearing potential, i.e. females aged between 18 and 45 years (pre-menopausal).

Official Title
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The Effect of Prucalopride on the Plasma Levels of Oral Contraceptives (Ethinylestradiol and Norethisterone) in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: prucalopride


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Subjects who meet all of the following criteria are eligible for this trial: Healthy females, aged between 18 and 45 years extremes included, who have regular menstrual cycle of 28 ± 3 days for the last 6 months. Adequate use of non-hormonal birth control (double-barrier method (e.g. condom and spermicide, cervical cap and spermicide) or sterilization or vasectomy of the partner or certified abstinence). Subjects are not smoking for at least 6 months prior to selection. A body mass index (BMI) between 18 and 27 kg/m2, extremes included. The subject is in good health based on a pre-trial physical and gynaecological examination, medical history, anamnesis, electrocardiogram (ECG) and the results of biochemistry, coagulation or haematology tests or a urinalysis carried out within 4 weeks before the start of the trial. If the results of the biochemistry, coagulation or haematology tests or the urinalysis are not within the laboratory's reference ranges the subject will be included only on condition that the investigator judges that the deviations are not clinically significant. Subjects voluntarily signed written Informed Consent Form (ICF) in accordance with the regional laws or regulations, prior to the first trial related activity, indicating an understanding of the purpose of this trial. Subjects are willing to adhere to the treatment regimen and trial procedures described in this protocol. Exclusion criteria Subjects meeting any of the following criteria will be excluded from the trial: History, evidence or suspicion of alcohol or drug abuse (screening and Day -1). History or evidence of cardiac arrhythmias, bronchospastic or cardiovascular disease (e.g. ischemic heart disease or cerebrovascular accident), hepatic or gastrointestinal, renal or endocrine (diabetes mellitus, thyrotoxicosis), or neurological (Parkinsonism) or psychiatric, gynaecological or dermatological disease, drug allergy. Clinical significant abnormal ECG-intervals of morphology of the ECG, QT >500 ms or QTcB>470 ms. Use of concomitant medication or oral contraceptives within 6 weeks prior to screening, or any hormonal depot-device within 6 months prior to screening . All medication, with the exception of paracetamol should be stopped. Participation in an investigational drug trial in 30 days prior to the first visit. Donation of blood in the 60 days preceding the first visit. Pregnancy (as confirmed by a HCG test during screening and at Day 1 of each treatment session before dosing) or breast feeding. Subjects with positive results for HIV, hepatitis B or C at screening. Known allergy to the trial drugs ingredients/excipients. Subject has contraindications for the use of oral contraceptives (known or suspected active venous thrombo-embolic disorder, known or suspected hormone dependent malignancies, undiagnosed vaginal bleeding, coagulation disorders, menstrual cycle depending migraine, lipid metabolism disorders, hepatic disorders)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: oral contraceptives without prucalopride<br> | |
| Active Comparator: oral contraceptives with prucalopride<br>prucalopride | Drug: prucalopride<br>* prucalopride 2 mg oral dosing o.d. for 6 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma levels oral contraceptives |  | first days | 
| Plasma levels oral contraceptives after steady state |  | 5 days |