Progesterone Microspheres Pharmacokinetic - Pharmacodynamic (PK-PD) Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roberto Bernardo Escudero, Productos Científicos S. A. de C. V.
ClinicalTrials.gov Identifier:
NCT01176175
First received: August 4, 2010
Last updated: October 12, 2011
Last verified: October 2011
  Purpose

Phase: I pharmacokinetic - pharmacodynamic (PK-PD) study. Main objective: To establish the minimum effective dose of progesterone microspheres suspension, which administered by weekly intramuscular injection, will be able to induce transformation from a proliferative endometrium to a secretory endometrium.

Study design: Randomized, controlled, open-label, parallel, dose-response clinical trial.

Sites: 1 Subjects: 48 postmenopausal women.


Condition Intervention Phase
Infertility
Drug: Progesterone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Controlled, Open-label, Parallel, Clinical Trial to Assess Pharmacokinetics and Endometrial Effect of an Injectable Formulation of Progesterone Microspheres in Doses of 50 mg, 100 mg, 200 mg and 300 mg, in Postmenopausal Women.

Resource links provided by NLM:


Further study details as provided by Productos Científicos S. A. de C. V.:

Primary Outcome Measures:
  • Endometrial dating through histopathologic criteria. [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    Endometrial dating according Noyes criteria as a measure of efficacy. At the moment of the biopsy, study subjects would have received 25 days of estradiol valerate pretreatment and 10 days of progesterone (investigational product); thus simulating the 25th day of a menstrual cycle. Efficacy will be measured as number of biopsies that have histological date according to cronological date.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 0 -60 days. ] [ Designated as safety issue: No ]
    Progesterone plasmatic concentrations and pharmacokinetic parameters.

  • Adverse events [ Time Frame: 0 - 65 days ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events as a Measure of Safety and Tolerability Pain Scores on a Visual Analog Scale


Enrollment: 48
Study Start Date: August 2010
Study Completion Date: February 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 50 mg
Progesterone microspheres injectable suspension 50 mg
Drug: Progesterone
Progesterone microspheres injectable suspension 50 mg, intramuscular weekly injection for a total of 7 doses.
Experimental: 100 mg
Progesterone microspheres injectable suspension 100 mg
Drug: Progesterone
Progesterone microspheres injectable suspension 100 mg, intramuscular weekly injection for a total of 7 doses.
Experimental: 200 mg
Progesterone microspheres injectable suspension 200 mg
Drug: Progesterone
Progesterone microspheres injectable suspension 200 mg, intramuscular weekly injection for a total of 7 doses.
Experimental: 300 mg
Progesterone microspheres injectable suspension 300 mg
Drug: Progesterone
Progesterone microspheres injectable suspension 300 mg, intramuscular weekly injection for a total of 7 doses.

Detailed Description:

Sites: 1 Phase: 1 Main objective:To establish the minimum effective dose of progesterone microspheres suspension, which administered by weekly intramuscular injection, will be able to induce transformation from a proliferative endometrium to a secretory endometrium.

Secondary objectives:

  • To determine and compare the steady-state pharmacokinetic profile of investigational products.
  • To evaluate safety profile of investigational products in the study subjects.
  • To evaluate local tolerability of investigational products in the study subjects.

Study design:Randomized, controlled, open-label, parallel, dose-response clinical trial.

Investigational products:

  • Progesterone microspheres intramuscular injectable suspension 50 mg
  • Progesterone microspheres intramuscular injectable suspension 100 mg
  • Progesterone microspheres intramuscular injectable suspension 200 mg
  • Progesterone microspheres intramuscular injectable suspension 300 mg Study subjects: 48 healthy postmenopausal women, 45 - 60 years. Brief description: After written informed consent, 48 eligible women will receive pretreatment with oral estradiol valerate, then, 14 days later, those with adequate endometrial thickness evaluated through ultrasound will be randomized to study treatments (one IM injection each 7 days, for a total of 7 doses). 10 days after the first progesterone dose, an endometrial biopsy will be obtained. Blood samples will be obtained for pharmacokinetic study.
  Eligibility

Ages Eligible for Study:   45 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female
  • 45 to 60 years old
  • Able to read and write
  • Postmenopausal
  • Body Mass Index equal or below 34.99 kg/m2
  • Healthy
  • Normal uterus
  • Time availability

Exclusion Criteria:

  • Hypersensitivity to progesterone or related compounds
  • Hypersensitivity to estrogens
  • Hysterectomy
  • History or present hormone-dependent tumor
  • History or present uterine cervix dysplasia
  • Abnormal and clinically-significant laboratory test results
  • Family history of breast cancer
  • History of thromboembolic disease
  • Non-controlled hypertension
  • History of stroke
  • History of cardiac valve surgery
  • Renal failure
  • Hepatic failure
  • Non-controlled diabetes
  • Severe gastrointestinal disease
  • History of serious neurologic disease
  • Reduced mobility
  • Anemia
  • Previous or concomitant hormonal therapy
  • Previous or concomitant therapy with inhibitors or inductors of cytochrome
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01176175

Locations
Mexico
Asociación Mexicana para la Investigación Clínica, A. C. (AMIC)
Pachuca, Hidalgo, Mexico, 42090
Sponsors and Collaborators
Productos Científicos S. A. de C. V.
Investigators
Principal Investigator: Roberto Bernardo, MD MSc Asociación Mexicana para la Investigación Clínica, A. C. (AMIC)
  More Information

No publications provided

Responsible Party: Roberto Bernardo Escudero, Principal Investigator, Productos Científicos S. A. de C. V.
ClinicalTrials.gov Identifier: NCT01176175     History of Changes
Other Study ID Numbers: 0908/I/PRO
Study First Received: August 4, 2010
Last Updated: October 12, 2011
Health Authority: Mexico: Ministry of Health

Keywords provided by Productos Científicos S. A. de C. V.:
Progesterone
Microspheres
postmenopausal
Luteal phase support

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014