Clinical trial NCT02516631: Comparative Bioavailability Study of Two Misoprostol Formulations
Official title: A Comparative, Open-label, Parallel Design, Bioavailability Study of Two Misoprostol Formulations (Angusta™ 25 µg Dispersible Tablets vs. Cytotec® 200 µg Tablets) Following Single Oral or Sublingual Administration and Comparison of Safety of the Two Formulations Following Repeat Dosing Until Labour
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Labour, Induced
Keywords: Labour, induced
Misoprostol
Pharmacokinetics
Cardiotocography
Safety
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2015-08-06
Enrollment: 72
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare pharmacokinetics of two formulations of misoprostol following single dose administration in adult women being given misoprostol for cervical ripening and induction of labour.

Detailed description: Prostaglandin E2 (dinoprostone) given vaginally or intra-cervically, and oxytocin have been the most commonly used preparations for induction of labour. Misoprostol is a synthetic prostaglandin E1 analogue. Misoprostol has anti-secretory and mucosal protective properties and was originally developed in the 1970s for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers. It is now used much more widely for 'off-label' indications like medication abortion, medical management of miscarriage, cervical ripening before surgical procedures, treatment of postpartum hemorrhage, and induction of labour. The lack of a specific license for Cytotec® to be used in obstetrics and gynecology has led to a number of problems regarding correct dose and dose regime.

The study is an open-label, randomized, single-dose, comparative, parallel design, bioavailability study followed by repeat dosing of of two formulations misoprostol in healthy adult females being induced to go into labour.

The drug shall be administered orally or sublingually.

Eligibility criteria: Inclusion Criteria:

* Adult females
* Women wanting to participate and having given informed consent
* Known to have reached week 37 + 0 days to week 42 + 2 days of gestation
* With a viable fetus in a vertex position
* Age above or equal to 18 years old
* Women opting for vaginal delivery
* BMI between 20 and 30 kg/m2

Exclusion Criteria:

* Women with known allergy to misoprostol or other prostaglandins
* Women with prior caesarean section
* Women with dead or anomalous fetus
* Women with twin pregnancy
* Women with known liver or renal dysfunction

Primary outcomes:
measure: AUC (area under the curve) 0-t misoprostol
timeFrame: For 2 hours regime: pre-dose, 5, 10, 20, 30, 40, 50, 75, 100 and 120 min post-dose. For 4-hours regime at pre-dose, 5, 10, 20, 30, 40, 50, 75, 100,120, 180 and 240 min post-dose
measure: AUC (area under the curve) 0-inf of misoprostol
timeFrame: For 2 hours regime: pre-dose, 5, 10, 20, 30, 40, 50, 75, 100 and 120 min post-dose. For 4-hours regime at pre-dose, 5, 10, 20, 30, 40, 50, 75, 100,120, 180 and 240 min post-dose
Secondary outcomes:
measure: t max (Time to maximum) of misoprostol
timeFrame: For 2 hours regime: pre-dose, 5, 10, 20, 30, 40, 50, 75, 100 and 120 min post-dose. For 4-hours regime at pre-dose, 5, 10, 20, 30, 40, 50, 75, 100,120, 180 and 240 min post-dose
measure: t 1/2 (Elimination half-life) of misoprostol
timeFrame: For 2 hours regime: pre-dose, 5, 10, 20, 30, 40, 50, 75, 100 and 120 min post-dose. For 4-hours regime at pre-dose, 5, 10, 20, 30, 40, 50, 75, 100,120, 180 and 240 min post-dose
measure: APGAR score of infant
timeFrame: At time of birth
measure: Cardiotochographic (CTG) monitoring.
timeFrame: During labour
measure: Adverse event / Serious Adverse event profile.
timeFrame: From screening and until 7 days post treatment.
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital Lund
Study officials:
affiliation: Region Skåne
name: Dag Wide-Swensson
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amini M, Reis M, Wide-Swensson D. A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration. Front Pharmacol. 2020 Feb 12;11:50. doi: 10.3389/fphar.2020.00050. eCollection 2020.