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.
Overview
- Phase
- Phase 1
- Intervention
- Progesterone
- Conditions
- Infertility
- Sponsor
- Productos Científicos S. A. de C. V.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Endometrial dating through histopathologic criteria.
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
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.
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.
Investigators
Roberto Bernardo Escudero
Principal Investigator
Productos Científicos S. A. de C. V.
Eligibility Criteria
Inclusion Criteria
- •45 to 60 years old
- •Able to read and write
- •Postmenopausal
- •Body Mass Index equal or below 34.99 kg/m2
- •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
Arms & Interventions
50 mg
Progesterone microspheres injectable suspension 50 mg
Intervention: Progesterone
100 mg
Progesterone microspheres injectable suspension 100 mg
Intervention: Progesterone
200 mg
Progesterone microspheres injectable suspension 200 mg
Intervention: Progesterone
300 mg
Progesterone microspheres injectable suspension 300 mg
Intervention: Progesterone
Outcomes
Primary Outcomes
Endometrial dating through histopathologic criteria.
Time Frame: 10 days
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 Outcomes
- Pharmacokinetics(0 -60 days.)
- Adverse events(0 - 65 days)