Pharmacokinetics of a Novel Vaginal Delivery System for Testosterone and Dehydroepiandrosterone (DHEA)

Laboratorios Andromaco

Status and phase: Completed; Phase 1

Conditions: Hormone Deficiency; Pharmacokinetics

Treatments: Drug: Dehydroepiandrosterone 2.2 g; Drug: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg; Drug: Testosterone Topical Gel; Drug: Dehydroepiandrosterone Oral Capsule; Drug: Testosterone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03967964

PKAVD+T

EC1503 (Other Identifier)

Details and patient eligibility

About

This study was performed to determine the pharmacokinetic parameters of vaginal rings that contain DHEA, testosterone, or combinations of both androgens, in comparison to the oral administration of DHEA and the transdermal administration of testosterone.

Enrollment: 46 patients

Sex: Female

Ages: 40 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Women between 40 to 60 years old.
• Postmenopausal with spontaneous amenorrhea of 1 year or more, regardless of follicle stimulating hormone (FSH) levels; or amenorrhea of 6 to 12 months, in which the postmenopausal state will be confirmed with a FSH level of 0.040 international units per milliliter or higher.
• Body Mass Index between 19 and 30.
• Intact uterus.
• Not having received hormone therapy in the month prior to selection.
• Adequate veins to conduct serial blood samplings.
• Recent Pap smear (not more than 12 months), with a result negative for malignant neoplastic cells, and that contains sufficient endocervical cells for analysis. If the Pap smear was performed more than 12 months ago or cannot be verified through clinical documentation, it must be repeated during the selection process.
• Normal mammogram, BI.RADS I or II (American College of Radiology), within the last year. If the mammogram was performed more than 12 months ago or cannot be verified through clinical documentation, it must be repeated during the selection process.
• That provide written informed consent.

Exclusion criteria

• Use at randomization of phenytoin, barbiturates, primidone, carbamazepine, rifampin, griseofulvin, ketoconazole, lipid-lowering agents.
• History of diseases such as coronary heart disease, breast cancer, uterine cancer, and/or chronic hepatic disease.
• Unconscious volunteers, severely ill, or with mental disability.
• Allergy and hypersensitivity to DHEA and/or testosterone.
• Untreated or uncontrolled hypertension, with systolic pressure above 140 mm Hg or diastolic pressure above 90 mm Hg.
• Current participation in other research at the moment of the screening visit, or having concluded their participation in a previous research in less than 30 days since their last visit.
• Pregnant or lactating women; pregnancy must be confirmed with a urine positive human chorionic gonadotropin (HCG) test during screening.
• History of vein thrombosis (deep vein thrombosis, pulmonary embolism).
• History of arterial thrombosis (myocardial infarction) or prodromic conditions (e.g. transient ischemic attack, angina pectoris).
• History of stroke.
• History of migraine with focal neurological manifestations.
• History of hepatic tumor (benign or malignant).
• History of clinical atherosclerosis in first grade relatives (parents, siblings, sons [men less than 55 years old and women less than 65 years old]).
• Smoking (5 or more cigarettes a day).
• Diabetes mellitus that will be ruled out at screening if fasting glucose is less than 100 mg/dL or between 100 and 125 mg/dL, with Oral Glucose Tolerance Test that rules out diabetes. Diabetes will be confirmed with blood glucose equal to or above 200 mg/dL or 2 fasting glucose tests equal to or above 126 mg/dL.
• High density lipopolysaccharide (HDL)-cholesterol below 35 mg/dL.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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46 participants in 5 patient groups

Group 1: AVD

Experimental group

Description:

Vaginal ring with 2.2 grams dehydroepiandrosterone (DHEA), wearing time 72 hours

Treatment:

Drug: Dehydroepiandrosterone 2.2 g

Group 2: AVT

Experimental group

Description:

Vaginal ring with 35 mg testosterone, wearing time 72 hours.

Treatment:

Drug: Testosterone

Group 3: AVD+T

Experimental group

Description:

Vaginal ring with 1.5 grams DHEA and 25 mg testosterone, wearing time 72 hours.

Treatment:

Drug: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg

Group 4: DHEA capsule

Active Comparator group

Description:

Capsules with 25 mg DHEA, oral administration every 8 hours for a 72-hour period.

Treatment:

Drug: Dehydroepiandrosterone Oral Capsule

Group 5: Testosterone transdermal gel

Active Comparator group

Description:

Testosterone transdermal gel with dosing valve (pump): administration of 3 pump actuations (equivalent to 5 mg of testosterone each) per day (total daily dose 15 mg), on 3 consecutive days (72 hours).

Treatment:

Drug: Testosterone Topical Gel