Pharmacokinetics of Injectable Estradiol and Progesterone Microspheres Suspension

Multiple-dose Pharmacokinetic Study of Two Aqueous Suspensions of Estradiol and Progesterone Microspheres (1 mg/20 mg & 0.5 mg/15 mg) for Intramuscular Administration, in Postmenopausal Volunteers.

Phase I pharmacokinetic study

Main objective:

To determine plasmatic profiles and pharmacokinetic parameters of estradiol and progesterone on each of the formulations studied, after multiple-dose administration

Study design:

Randomized, controlled, open-label, parallel, pharmacokinetic study

Sites: 1

Subjects: 30 postmenopausal women

Study Overview

• Status: Completed
• Conditions: Menopause
• Intervention / Treatment: Drug: Estradiol + Progesterone; Drug: Estradiol + Progesterone

Detailed Description

Sites: 1

Phase: 1

Main objective:

To determine plasmatic profiles and pharmacokinetic parameters of estradiol and progesterone on each of the formulations studied, after multiple-dose administration.

Secondary objectives:

To determine bioavailability of each of the formulations studied, after multiple-dose-administration. Describe tolerability of each of the formulations studied, after multiple-dose administration.

Study design: Randomized, controlled, open-label, parallel, pharmacokinetic study

Investigational Products:

• Estradiol and progesterone microspheres aqueous suspension (1 mg/20 mg)
• Estradiol and progesterone microspheres aqueous suspension (0.5 mg/15 mg)

Study subjects: 30 postmenopausal women 45 - 65 years old

Brief description: After written informed consent, 30 eligible women will be randomized to study treatments (one IM injection each 28 days, for a total of 4 doses). Blood samples will be obtained for pharmacokinetic study.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• 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 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female
• 45 to 65 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
• History of serious neurologic disease
• Reduced mobility
• Anemia
• Previous or concomitant hormone 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estradiol 0.5 mg/Progesterone 15 mg microspheres; Estradiol 0.5 mg and progesterone 15 mg microspheres injectable aqueous suspension	Drug: Estradiol + Progesterone; Estradiol 1 mg and progesterone 20 mg microspheres injectable aqueous suspension, intramuscular monthly injection for a total of 4 doses.; Drug: Estradiol + Progesterone; Estradiol 0.5 mg and progesterone 15 mg microspheres injectable aqueous suspension, intramuscular monthly injection for a total of 4 doses.
Experimental: Estradiol 1 mg/Progesterone 20 mg microspheres; Estradiol 1 mg and progesterone 20 mg microspheres injectable aqueous suspension	Drug: Estradiol + Progesterone; Estradiol 1 mg and progesterone 20 mg microspheres injectable aqueous suspension, intramuscular monthly injection for a total of 4 doses.; Drug: Estradiol + Progesterone; Estradiol 0.5 mg and progesterone 15 mg microspheres injectable aqueous suspension, intramuscular monthly injection for a total of 4 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Estrogen and progesterone plasma concentrations and pharmacokinetic parameters.	0 - 60 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Number of Participants with Adverse Events as a Measure of Safety and Tolerability. Adverse events will be evaluated through periodic clinical evaluations and laboratory tests (comparison between enrollment and discharge).	0 - 60 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: February 10, 2011
• First Posted (Estimate): February 11, 2011

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: Pharmacokinetics; Menopause; Microspheres; Progesterone; Estrogen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Estradiol; Progesterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 0903/I/PRO