Feasibility Study Into the Contraceptive Effect of Estetrol - Full Text View

Sponsor:	Pantarhei Bioscience
Information provided by:	Pantarhei Bioscience
ClinicalTrials.gov Identifier:	NCT00563472

Purpose

This is an open study in 50 young, healthy, female volunteers. Women who want to participate and who are using hormonal contraception stop using their hormonal contraceptive and wait for their first spontaneous menstruation (i.e. after a wash-out cycle). Women who do not use hormonal contraception wait for their next menstruation. From the 9th day after start of the menstruation onwards follicle growth will be monitored by ultrasonography until ovulation occurs or until day 24 after start of their menses. Women who ovulate within 24 days after start of their menses will be eligible to participate and will be stratified in one of 4 groups: 10 mg estetrol (E4) alone, 20 mg E4 alone, 20 mg E4 combined with 150 mcg desogestrel and 20 mg E4 combined with 200 mg progesterone. The subjects will be treated for 28 days. Treatment will start on the first day of their menses after the pre-treatment cycle.

During the study period (28 days) the activity of the hypothalamic-pituitary-ovarian (HPO) axis will be investigated by measuring follicular development using ultrasonography and by determining serum concentrations of Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), estradiol (E2) and Progesterone (P).

Condition	Intervention	Phase
Healthy	Drug: estetrol Drug: estetrol and desogestrel Drug: estetrol and progesterone	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	A Feasibility Study Into the Contraceptive Effect of Estetrol Alone or Combined With Either Progesterone or Desogestrel by Daily Oral Administration to Healthy Female Volunteers for 28 Days.

Resource links provided by NLM:

MedlinePlus related topics: Menstruation

Drug Information available for: Progesterone Desogestrel

U.S. FDA Resources

Further study details as provided by Pantarhei Bioscience:

Primary Outcome Measures:

ovulation inhibition [ Time Frame: during treatment ]

Secondary Outcome Measures:

endocrine parameters [ Time Frame: during treatment ]

Estimated Enrollment:	50
Study Start Date:	November 2007
Estimated Study Completion Date:	May 2008

Arms	Assigned Interventions
1: Active Comparator 10 mg estetrol	Drug: estetrol 10 mg orally per day for 28 days
2: Active Comparator 20 mg estetrol	Drug: estetrol 20 mg orally per day for 28 days
3: Active Comparator 20 mg estetrol and 150 microg desogestrel	Drug: estetrol and desogestrel 20 mg estetrol and 150 microg desogestrel orally per day for 28 days
4: Active Comparator 20 mg E4 and 200 mg progesterone	Drug: estetrol and progesterone 20 mg estetrol and 200 mg progesterone orally per day for 28 days

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

At least 18 years and not older than 40 years of age
Willing to use a barrier method of contraception during the wash-out cycle, the pre-treatment cycle, the period of study drug administration, the period of lynestrenol intake (if applicable), and 14 days thereafter or until the follow-up visit if this 14-days period ends before the follow-up visit.
Women who ovulate in the pre-treatment cycle before or on day 24 (±1) after start of their menses, who have a subsequent P concentration of > 16 nmol/l and whose next menstruation does not start within 6 days after ovulation
Body Mass Index > 18 and <30 kg/m2
Good physical and mental health
Both ovaries visible upon ultrasonography
Willing to give informed consent in writing

Exclusion Criteria:

Clinically significant abnormal results of routine hematology, serum biochemistry, urinanalysis, and/or ECG in the opinion of the Investigator at screening.
Known or suspected pregnancy
Lactation
Pregnancy during accurate hormonal contraceptive use
Known or suspected breast cancer or a history of breast cancer
Clinically significant abnormalities of the uterus and/or ovaries detected by examination and/or ultrasound (non-physiological ovarian mass or significant uterine pathology).
A cervical smear with clinically relevant abnormal cytology within one year before study start.
Previous use of depot progestogen preparations in the last 6 months.
Contraindications for contraceptive steroids:
- a history of, or existing thromboembolic, cardiovascular or cerebrovascular disorder
- a history of, or existing conditions predisposing to, or being prodromi of, a thrombosis
- a known defect in the blood coagulation system (e.g. deficiencies in AT-III, protein C, S, and APC resistance)
- heterozygous for a mutation in coagulation factor II and/or positive for factor V Leiden
- the presence of a severe or more than one risk factor for vascular disease (e.g. dyslipoproteinaemia; diabetes mellitus; hyperhomocysteinaemia; systemic lupus erythematosus; chronic inflammatory bowel disease; antiphospholipid antibodies; smoking; venous thromboembolism in sibling or parent below the age of 50, or arterial disease in sibling or parent below the age of 35; within 2 weeks after full remobilisation following surgery)
- hypertension, i.e. systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg
- disturbance of liver function: e.g. cholestatic jaundice, a history of jaundice of pregnancy or jaundice due to previous oestrogen use, Rotor syndrome and Dubin-Johnson syndrome
- known or suspected hormone-dependent tumours or endometrial hyperplasia
- undiagnosed vaginal bleeding
- porphyria
- a history during pregnancy or previous hormone-use of severe pruritus, herpes gestationis or deterioration of otosclerosis
Use of one or more of the following medications:
- sex steroids other than the medication of study
- use at present or within 2 months before start study medication:
- hydantoins, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, troglitazone, felbamate, rifampicin, rifabutin, griseofulvin and St. John's wort (Hypericum perforatum)
Status post-partum or post-abortion within a period of 2 months before study start
Administration of investigational drugs within 3 months before start study medication
A history of (within 12 months) alcohol or drug abuse
A known hypersensitivity for one of the components of the study medication (eg arachisoil and lactosis)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00563472

Locations

Netherlands
Dinox	Recruiting
Groningen, Netherlands, 9713 GZ
Contact: I. Duijkers, MD, PhD +31 50 3610900
Contact: C. Klipping, MD, PhD +31 50 3610900
Principal Investigator: C. Klipping, MD, PhD
Principal Investigator: I. Duijkers, MD, PhD

Sponsors and Collaborators

Pantarhei Bioscience

Investigators

Study Director:

H. Coelingh Bennink, MD, PhD

Pantarhei Bioscience

More Information

No publications provided

Study ID Numbers:	PR3081
Study First Received:	November 22, 2007
Last Updated:	November 23, 2007
ClinicalTrials.gov Identifier:	NCT00563472 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Pantarhei Bioscience:

Healthy female volunteers will participate in this study

Additional relevant MeSH terms:

Progesterone
Contraceptive Agents
Physiological Effects of Drugs
Contraceptives, Oral
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female
Reproductive Control Agents

Hormones
Pharmacologic Actions
Desogestrel
Therapeutic Uses
Progestins
Contraceptives, Oral, Synthetic

ClinicalTrials.gov processed this record on February 08, 2010