Progesterone Microspheres Pharmacokinetic - Pharmacodynamic (PK-PD) Study

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.

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.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Progesterone; Drug: Progesterone; Drug: Progesterone; Drug: Progesterone

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Hidalgo
    • Pachuca, Hidalgo, Mexico, 42090
      • Asociación Mexicana para la Investigación Clínica, A. C. (AMIC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.; Drug: Progesterone; Progesterone microspheres injectable suspension 100 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 200 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 300 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 50 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 100 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 200 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 300 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 50 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 100 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 200 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 300 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 50 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 100 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 200 mg, intramuscular weekly injection for a total of 7 doses.; Drug: Progesterone; Progesterone microspheres injectable suspension 300 mg, intramuscular weekly injection for a total of 7 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial dating through histopathologic criteria.	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.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Progesterone plasmatic concentrations and pharmacokinetic parameters.	0 -60 days.
Adverse events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability Pain Scores on a Visual Analog Scale	0 - 65 days

Collaborators and Investigators

• Sponsor: Productos Científicos S. A. de C. V.
• Investigators: Principal Investigator: Roberto Bernardo, MD MSc, Asociación Mexicana para la Investigación Clínica, A. C. (AMIC)

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: August 4, 2010
• First Submitted That Met QC Criteria: August 4, 2010
• First Posted (Estimate): August 5, 2010

Study Record Updates

• Last Update Posted (Estimate): October 13, 2011
• Last Update Submitted That Met QC Criteria: October 12, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: postmenopausal; Microspheres; Progesterone; Luteal phase support
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 0908/I/PRO