Endometrial Effects of Daily Progesterone s.c. 25 and 50 Mg Aqueous Formulation to Female Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy

• Registration Number: NCT00377923
• Lead Sponsor: IBSA Institut Biochimique SA

Brief Summary

This is a multiple dose, observer blind, randomised, parallel groups pharmacodynamic and pharmacokinetic study to assess the endometrial effects (predecidual changes) of a new aqueous progesterone formulation administered s.c. at the dose of 25 and 50 mg/day.

Detailed Description

This study is designed in order to assess the efficacy of the investigational product (Progesterone acqueous s.c. formulation) when it is administered at the dose of 25 and 50 mg. The induced predecidual changes will be evaluated through endometrial bioptic samplings, performed on day 11 and will be compared between the two treatment groups.

The pharmacokinetic evaluation was designed according to internationally recognised guidelines for PK studies.

Study Timeline

• Study Start: 2005-08
• Study Completion: 2006-03
• Status Verified: 2006-09
• Study First Submitted: 2006-09-18
• Study First Submitted QC: 2006-09-18
• Study First Posted: 2006-09-19
• Last Update Submitted: 2006-09-19
• Last Update Posted: 2006-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 24

Inclusion Criteria

• BMI: 19</=BMI</=25 kg/m2;
• Proper estrogen priming; absence of progesterone exposure prior to exogenous progesterone administration;
• normal pelvic ultrasound;
• absence of active follicular growth following initiation of E2 treatment;
• Complete suppression of ovarian function;
• Vital signs: SBP 100-139 mmHg, DBP 50-89, HR 50-90 bpm;
• Full comprehension of the nature and purpose of the study and possible risks and side effects;
• signed written informed consent prior to inclusion in the study

Exclusion Criteria

• pregnant or lactating women;
• ECG: clinically relevant abnormalities;
• clinical relevant abnormal physical findings which could interfere with the objectives of the study;
• clinical relevant abnormal laboratory values indicative of physical illness, ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients;
• history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study;
• history of uterine pathologies (fibroids, polyps, adenomyosis, etc), history of dysfunctional bleeding, relevant history of renal, hepatic, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases, history of neoplasias (genital apparatus, breast, liver or hormone-dependent cancer) severe liver failure, acute or chronic liver dysfunction, cholestatic jaundice, hypertension, thrombo-phlebitis, thrombo-embolism, cerebro-vascular insult or severe depression; medication, including OTC, during 2 weeks before the start of the study;
• participation in the evaluation of any drug within 1 month prior to the start of the study;
• blood donations during the 1 month prior to this study;
• history of drug, alcohol [>1 drink/day defined according to USDA Dietary Guidelines 2005 (18)] caffeine (>5 cups/ day of coffee or tea) or tobacco abuse (≥10 cigarettes/day);
• Abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits within the past 4 weeks.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
partial and full predecidual changes in endometrial samples on the 11th day of exposure to the IMP compared to the findings on the 11th day after ovulation in the menstrual cycle, according to Noyes criteria

Secondary Outcome Measures

Name	Time	Method
PK profile of progesterone at the steady-state following the 25 or 50 mg/day of progesterone s.c. at the time of endometrial biopsy, local tolerability