Cycle Control Assessment of a Combined Oral Contraceptive Containing Estetrol and a Progestin P1 or P2 (FIESTA)

A Randomised Open-label Multi-centre Comparative Study to Evaluate Cycle Control of 2 Dosages of Estetrol Combined With Either P1 or P2, Compared to a Combined Oral Contraceptive Containing E2V and DNG

This is an open-label, multi-centre, comparative study in young, healthy, female volunteers of reproductive age.

Primary objective:

- To investigate the effect of 2 dosages of estetrol combined with P1 or P2, on vaginal bleeding patterns (cycle control), in comparison with a combined oral contraceptive containing estradiol valerate and dienogest

Secondary objectives:

• To investigate ovulation inhibition
• To investigate the effect on SHBG
• To assess pregnancy rate
• To evaluate subject satisfaction, dysmenorrhoea, acne, and body weight
• To investigate return of menstruation after treatment
• To evaluate general safety and acceptability

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: estetrol, P 1 and placebo tablets; Drug: estetrol, P2 and placebo tablets; Drug: Estradiol valerate, dienogest and placebo tablets

• Study Type: Interventional
• Enrollment (Actual): 396
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Mehiläinen Helsinki
  • Helsinki, Finland
    • Väestöliitto Helsinki
  • Jyvaskyla, Finland
    • YTHS Jyvaskyla
  • Kuopio, Finland
    • Laboratorio Simpanen
  • Kuopio, Finland
    • Terveystalo Kuopio
  • Kuopio, Finland
    • YTHS Kuopio
  • Oulu, Finland
    • Väestöliitto Oulu
  • Tampere, Finland
    • Tampereen Lääkärikeskus Oy
  • Tampere, Finland
    • YTHS Tampere
  • Turku, Finland
    • Väestöliitto Turku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women willing to use a Combined Oral Contraceptive for 6 subsequent cycles
• Good physical and mental health
• Regular menstrual cycle (24-35 days) prior to screening
• Body mass index between (≥) 18 and (≤) 30 kg/m2

Exclusion Criteria:

• Previous use of any hormonal contraceptive method during the last 3 months prior to randomisation (only applicable for women who are not using a hormonal contraceptive method at the time of screening)
• Previous use of progestogen-only contraceptive methods during the last 3 months or during the last 6 months for depot progestogen preparations or an injectable hormonal method of contraception
• Use of phytoestrogens
• No spontaneous menstruation has occurred following a delivery or abortion
• Breastfeeding or within 2 months after stopping breastfeeding prior to the start of study medication and no spontaneous return of menstruation
• Status post-partum or post-abortion within a period of 2 months before screening
• Pregnancy during accurate hormonal contraceptive use in the past
• Intention to become pregnant during the study
• An abnormal cervical smear within one year before study start
• Untreated Chlamydia infection
• Known or suspected breast cancer or a history of breast cancer
• A history of (within 12 months) alcohol or drug abuse
• Any clinically relevant abnormality
• Contraindications for the contraceptive steroids used in the clinical trial
• Use of antihypertensive drugs or use of medications interacting with the contraceptive steroids used in the clinical trial
• Administration of any other investigational drug within 2 months prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: estetrol dose 1 / P1	Drug: estetrol, P 1 and placebo tablets; 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P1 tablet per day; Days 25-28: two placebo tablets per day
EXPERIMENTAL: estetrol dose 1 / P2	Drug: estetrol, P2 and placebo tablets; 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P2 tablet per day; Days 25-28: two placebo tablets per day
ACTIVE_COMPARATOR: estradiol valerate/dienogest pill	Drug: Estradiol valerate, dienogest and placebo tablets; 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-26: one tablet of Estradiol valerate/dienogest per day; Days 26-28: one placebo tablet per day
EXPERIMENTAL: estetrol dose 2 / P1	Drug: estetrol, P 1 and placebo tablets; 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P1 tablet per day; Days 25-28: two placebo tablets per day
EXPERIMENTAL: estetrol dose 2 / P2	Drug: estetrol, P2 and placebo tablets; 6 treatment cycles each consisting of 28 days of oral administration as follows: Days 1-24: one estetrol tablet and one P2 tablet per day; Days 25-28: two placebo tablets per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recording of vaginal bleeding events (diary) as a measure of Cycle control	6 cycles of 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of pregnandiol glucuronide in urine as a measure of Ovulation inhibition		6 cycles of 28 days
Patient Reported Outcome questionnaire as a measure of Subject satisfaction		6 cycles of 28 days
Contacts patient-investigator to document Return of menstruation	(only in case the patient does not start up a new hormonal contraceptive method or in case of pregnancy wish)	for up to 1 year follow-up
Recording of adverse events, physical examination and laboratory parameters as a measure of Safety and Tolerability		up to 8 months
Measurement of SHBG in blood samples to assess the effect of treatment on SHBG		6 cycles of 28 days
Reporting of in-treatment pregnancies as a measure of pregnancy rate		6 cycles of 28 days

Collaborators and Investigators

• Sponsor: Estetra
• Investigators: Principal Investigator: Dan Apter, M.D., Väestöliitto Helsinki

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: October 13, 2010
• First Submitted That Met QC Criteria: October 14, 2010
• First Posted (ESTIMATE): October 15, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): September 14, 2012
• Last Update Submitted That Met QC Criteria: September 13, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Dienogest
• Other Study ID Numbers: ES-C02; 2010-019865-26 (EUDRACT_NUMBER)