Clinical trial NCT03967964: Pharmacokinetics of a Novel Vaginal Delivery System for Testosterone and Dehydroepiandrosterone (DHEA)
Official title: Prospective, Randomized, Open-label and Comparative Study to Determine the Pharmacokinetic Parameters of Vaginal Rings That Contain DHEA, Testosterone, or the Combination of Both Androgens, in Comparison With Oral Administration of DHEA and Transdermal Administration of Testosterone, in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Hormone Deficiency
Keywords: Gynaecology
Obstetrics
Lead sponsor: Laboratorios Andromaco S.A.
Sponsor class: INDUSTRY
First posted: 2019-05-30
Enrollment: 46
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, randomized, open-label comparative, single-site study with 5 treatment groups. Each participant receives a single Treatment for 72 hours. Allocation to Treatment is in a 1:1:1:1:1 order.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Testosterone: Area under the serum concentration time curve (AUC0-72)
timeFrame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
measure: DHEA: Area under the serum concentration time curve (AUC0-72)
timeFrame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
measure: Testosterone: Average serum concentration 0-24 hours
timeFrame: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours
measure: DHEA: Average serum concentration 0-24 hours
timeFrame: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours
measure: Testosterone: Maximum serum concentration (Cmax)
timeFrame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
measure: DHEA: Maximum serum concentration (Cmax)
timeFrame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
measure: Testosterone: Time to achieve maximum serum concentration (tmax)
timeFrame: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
measure: DHEA: Time to achieve maximum serum concentration (tmax)
timeFrame: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Instituto de Investigación Materno Infantil (IDIMI) - Maternidad Hospital San Borja (HCSBA)
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References: