Progesterone Microspheres Pharmacokinetic - Pharmacodynamic (PK-PD) Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Infertility

Intervention / Treatment
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* Drug: Progesterone
* Drug: Progesterone
* Drug: Progesterone
* Drug: Progesterone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg<br>Progesterone microspheres injectable suspension 50 mg | Drug: Progesterone<br>* Progesterone microspheres injectable suspension 50 mg, intramuscular weekly injection for a total of 7 doses.<br>|
| Experimental: 100 mg<br>Progesterone microspheres injectable suspension 100 mg | Drug: Progesterone<br>* Progesterone microspheres injectable suspension 100 mg, intramuscular weekly injection for a total of 7 doses.<br>|
| Experimental: 200 mg<br>Progesterone microspheres injectable suspension 200 mg | Drug: Progesterone<br>* Progesterone microspheres injectable suspension 200 mg, intramuscular weekly injection for a total of 7 doses.<br>|
| Experimental: 300 mg<br>Progesterone microspheres injectable suspension 300 mg | Drug: Progesterone<br>* Progesterone microspheres injectable suspension 300 mg, intramuscular weekly injection for a total of 7 doses.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progesterone, Microspheres, postmenopausal, Luteal phase support