A phase I, open-label study to assess the pharmacokinetic profile, safety and tolerability of OBE001 after a single oral administration in pregnant women with medically indicated pregnancy terminatio

Withdrawn

Conditions: NA (healthy volunteers)
10010273

Registration Number: NL-OMON40897

Lead Sponsor: ObsEva SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

1.The Subject must provide written informed consent prior to initiation of any study related procedures, as shown by a signature on the volunteer consent form.
2.The Subject must be an adult woman aged from 18 and above at screening.
3.The Subject must be a healthy pregnant female volunteer.
4.The Subject must have a medically indicated pregnancy termination for fetal indication (e.g. genetic abnormality and/or congenital malformation).
5.The Subject must have a pregnancy with a gestational age (confirmed by US scan done prior Week 20+0/7) at the time of planned pregnancy termination being between 14+0/7 (inclusive) week and upper limit for legal pregnancy termination in the center country.
6.The Subject must have a singleton pregnancy.
7.The Subject must be non-smoker or must be a light smoker (less than 5 cigarettes per day). No smoking (or smoking substitute e.g. nicotine patch) is permitted from screening and throughout the study.
8.The Subject must be able to communicate well with the investigator and research staff and to comply with the requirements of the study protocol.

Exclusion Criteria

1.The Subject has a current pregnancy with a dead fetus.
2.The subject has a current pregnancy with an expected high risk of fetal death in the coming days, including severe fetal cardiac malformation, fetal cystic hygroma or hydrops fetalis.
3.The Subject had a BMI >= 35 kg/m2 prior to current pregnancy.
4.The Subject has a current body weight < 50kg.
5.The Subject has any condition, including findings in the medical history or in the pre-trial assessments, which in the opinion of the investigator constitutes a risk or a contraindication for the participation of the subject in the trial or that could interfere with the trial objectives, conduct or evaluation.
6.The Subject has any clinically significant abnormality in the results of the screening safety laboratory tests, including AST, ALT, GGT, alkaline phosphatase or total bilirubin above twice upper limit of normal. In case of isolated GGT increase, a single re-test is allowed.
7.The Subject has any clinically significant abnormality in the results of the screening physical examination which in the opinion of the Investigator could interfere with the trial objectives, conduct and evaluation.
8.The Subject has any clinically significant abnormality in the results of the screening gynaecological examination which in the opinion of the investigator could interfere with the trial objectives, conduct and evaluation.
9.The Subject has any clinically significant abnormality on the 12-lead ECG recording at screening.
10.The Subject has any clinically significant abnormality on arterial blood pressure (BP) or heart rate (HR) at screening.
11.The Subject has a known positive result from virology tests for hepatitis B surface antigen (HBsAg) (not due to vaccination), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2.
12.The Subject has a history or presence of clinically significant hypertension or other significant cardiovascular abnormality.
13.The Subject has a history or presence of significant kidney disease.
14.The Subject has a history of any significant acute infection in the four weeks before dosing.
15.The Subject has a history of serious allergy (i.e. that required hospitalization or systemic treatment), asthma, allergic skin rash or allergy to any of the ingredients of the OBE001 tablet (see list of ingredients in the Investigator*s Brochure).
16.The Subject has been administered with any experimental drug in the 12 weeks before dosing.
17.The Subject has forfeited her freedom by administrative or legal award or was under guardianship.
18.The Subject has known current problems with drug or alcohol abuse (more than 7 units of alcohol per week, one unit = 280 mL of beer (3-4°), 100 mL of wine (10-12°) or 30 mL of spirits (40°).
19.The Subject has lost or donated more than 400 mL of blood in the 12 weeks before dosing.
20.The Subject has used any prescription drugs or over-the-counter drugs (with the exception of paracetamol (up to 4 g per day), multi-vitamins, iron and folic acid) in the week before dosing, without prior approval from the investigator.
21.The Subject has consumed any substances known to be potent inhibitors or inducers of CYP P450s such as grapefruit juice, grapefruit juice-containing products, and herbal remedies or dietary supplements containing St. John*s Wort, in the week before dosing.
22.The Subject has participated in any

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The following pharmacokinetic variables will be calculated for each subject<br /><br>using the actual sampling intervals (relative to medication administration):<br /><br>- Maximum concentration (Cmax).<br /><br>- Area under the plasma drug concentration versus time curve to 24h post-dose<br /><br>time point (AUC 0-24) and to last measured time point (AUC last).<br /><br>- Area under the plasma drug concentration versus time curve with extrapolation<br /><br>to infinity (AUC0-).<br /><br>- Time to the maximum concentration (tmax).<br /><br>- Apparent terminal half-life (t1/2).<br /><br>- Terminal elimination rate (el)<br /><br>- Apparent volume of distribution after non-intravenous administration (Vd/F)<br /><br>- Apparent total clearance of the drug from plasma after oral administration<br /><br>(Cl/F)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Number and proportion of women experiencing treatment-emergent adverse events<br /><br>assessed by safety variables (clinically significant changes in laboratory<br /><br>safety tests, 12-lead ECGs morphology and time intervals, vital signs and other<br /><br>reported adverse events).<br /><br>- Number and proportion of fetus experiencing treatment-emergent major cardiac<br /><br>rhythm changes i.e. severe tachycardia (heart rate >= 160 bpm lasting for >= 5<br /><br>min), bradycardia (heart rate <= 80 bpm lasting for >= 5 min) or cardiac<br /><br>arrest.<br /><br>- Foeto-maternal exposure ratio at the time of delivery, based on time-matched<br /><br>sample collections from mother and fetus (umbilical cord vein).</p><br>