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

NCT00377923 | Completed Phase 1

• 1 other identifier: 05A/Prg05
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Healthy

Keywords

pharmacodynamic and pharmacokinetic study; Progesterone; healthy volunteers; Endometrial decidualisation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Interventions

Progesterone DRUG

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• IBSA Institut Biochimique SA: lead

Related Publications (16)

• de Ziegler D, Bouchard P. Understanding endometrial physiology and menstrual disorders in the 1990s. Curr Opin Obstet Gynecol. 1993 Jun;5(3):378-88.

  PMID: 8329654 BACKGROUND

• de Ziegler D, Bergeron C, Cornel C, Medalie DA, Massai MR, Milgrom E, Frydman R, Bouchard P. Effects of luteal estradiol on the secretory transformation of human endometrium and plasma gonadotropins. J Clin Endocrinol Metab. 1992 Feb;74(2):322-31. doi: 10.1210/jcem.74.2.1730810.

  PMID: 1730810 BACKGROUND

• NOYES RW, HAMAN JO. Accuracy of endometrial dating; correlation of endometrial dating with basal body temperature and menses. Fertil Steril. 1953 Nov-Dec;4(6):504-17. doi: 10.1016/s0015-0282(16)31446-7. No abstract available.

  PMID: 13107761 BACKGROUND

• Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975 May;122(2):262-3. doi: 10.1016/s0002-9378(16)33500-1. No abstract available.

  PMID: 1155504 BACKGROUND

• Soliman S, Daya S, Collins J, Hughes EG. The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials. Fertil Steril. 1994 Jun;61(6):1068-76. doi: 10.1016/s0015-0282(16)56758-2.

  PMID: 8194619 BACKGROUND

• Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002 Sep;17(9):2287-99. doi: 10.1093/humrep/17.9.2287.

  PMID: 12202415 BACKGROUND

• Bourgain C, Smitz J, Devroey P. Meta-analysis on luteal phase support. Hum Reprod. 2003 Mar;18(3):656; author reply 656-7. doi: 10.1093/humrep/deg098. No abstract available.

  PMID: 12615845 BACKGROUND

• Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;(3):CD004830. doi: 10.1002/14651858.CD004830.

  PMID: 15266541 BACKGROUND

• de Ziegler D, Cornel C, Bergeron C, Hazout A, Bouchard P, Frydman R. Controlled preparation of the endometrium with exogenous estradiol and progesterone in women having functioning ovaries. Fertil Steril. 1991 Nov;56(5):851-5. doi: 10.1016/s0015-0282(16)54654-8.

  PMID: 1936317 BACKGROUND

• Lelaidier C, de Ziegler D, Gaetano J, Hazout A, Fernandez H, Frydman R. Controlled preparation of the endometrium with exogenous oestradiol and progesterone: a novel regimen not using a gonadotrophin-releasing hormone agonist. Hum Reprod. 1992 Nov;7(10):1353-6. doi: 10.1093/oxfordjournals.humrep.a137572.

  PMID: 1291558 BACKGROUND

• Fanchin R, De Ziegler D, Bergeron C, Righini C, Torrisi C, Frydman R. Transvaginal administration of progesterone. Obstet Gynecol. 1997 Sep;90(3):396-401. doi: 10.1016/s0029-7844(97)00270-6.

  PMID: 9277651 BACKGROUND

• Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Fertil Steril. 1998 Jan;69(1):96-101. doi: 10.1016/s0015-0282(97)00457-3.

  PMID: 9457941 BACKGROUND

• Jobanputra K, Toner JP, Denoncourt R, Gibbons WE. Crinone 8% (90 mg) given once daily for progesterone replacement therapy in donor egg cycles. Fertil Steril. 1999 Dec;72(6):980-4. doi: 10.1016/s0015-0282(99)00390-8.

  PMID: 10593367 BACKGROUND

• Damario MA, Barmat L, Liu HC, Davis OK, Rosenwaks Z. Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Hum Reprod. 1997 Nov;12(11):2359-65. doi: 10.1093/humrep/12.11.2359.

  PMID: 9436663 BACKGROUND

• de Ziegler D, Fanchin R. Progesterone and progestins: applications in gynecology. Steroids. 2000 Oct-Nov;65(10-11):671-9. doi: 10.1016/s0039-128x(00)00123-9.

  PMID: 11108875 BACKGROUND

• de Ziegler D, Sator M, Binelli D, Leuratti C, Cometti B, Bourgain C, Fu YS, Garhofer G. A randomized trial comparing the endometrial effects of daily subcutaneous administration of 25 mg and 50 mg progesterone in aqueous preparation. Fertil Steril. 2013 Sep;100(3):860-6. doi: 10.1016/j.fertnstert.2013.05.029. Epub 2013 Jun 24.

  PMID: 23806850 DERIVED

MeSH Terms

Interventions

Progesterone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Markus Müller, Prof

  Department of Clinical Pharmacology, AKH, Vienna, Austria.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 18, 2006
• First Posted: September 19, 2006
• Study Start: August 1, 2005
• Study Completion: March 1, 2006
• Last Updated: September 20, 2006

Record last verified: 2006-09