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出境医 / 临床实验 / Pharmacokinetics of a Novel Vaginal Delivery System for Testosterone and Dehydroepiandrosterone (DHEA)

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

Study Description
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.

Condition or disease Intervention/treatment Phase
Pharmacokinetics Hormone Deficiency Drug: Dehydroepiandrosterone 2.2 g Drug: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg Drug: Testosterone Drug: Testosterone Topical Gel Drug: Dehydroepiandrosterone Oral Capsule Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 20, 2015
Actual Primary Completion Date : July 15, 2016
Actual Study Completion Date : July 15, 2016
Arms and Interventions
Arm Intervention/treatment
Experimental: Group 1: AVD
Vaginal ring with 2.2 grams dehydroepiandrosterone (DHEA), wearing time 72 hours
Drug: Dehydroepiandrosterone 2.2 g
Vaginal ring with 2.2 grams DHEA.

Experimental: Group 2: AVT
Vaginal ring with 35 mg testosterone, wearing time 72 hours.
Drug: Testosterone
Vaginal ring with 35 mg testosterone.

Experimental: Group 3: AVD+T
Vaginal ring with 1.5 grams DHEA and 25 mg testosterone, wearing time 72 hours.
Drug: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg
Vaginal ring with DHEA 1.5 grams/Testosterone 25 mg.

Active Comparator: Group 4: DHEA capsule
Capsules with 25 mg DHEA, oral administration every 8 hours for a 72-hour period.
Drug: Dehydroepiandrosterone Oral Capsule
Capsule containing 25 mg DHEA

Active Comparator: Group 5: Testosterone transdermal gel
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).
Drug: Testosterone Topical Gel
Gel containing 1% testosterone.
Other Name: ActiserPump®

Outcome Measures
Primary Outcome Measures :
  1. Testosterone: Area under the serum concentration time curve (AUC0-72) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The AUC0-72 was calculated.

  2. DHEA: Area under the serum concentration time curve (AUC0-72) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum DHEA were measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The AUC0-72 was calculated.

  3. Testosterone: Average serum concentration 0-24 hours [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The average serum concentration achieved in the first 24 hours after administration of the assigned treatment was calculated.

  4. DHEA: Average serum concentration 0-24 hours [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours ]
    Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The average serum concentration achieved in the first 24 hours after administration of the assigned treatment was calculated.

  5. Testosterone: Maximum serum concentration (Cmax) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Cmax was calculated.

  6. DHEA: Maximum serum concentration (Cmax) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Cmax was calculated.

  7. Testosterone: Time to achieve maximum serum concentration (tmax) [ Time Frame: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Tmax was calculated.

  8. DHEA: Time to achieve maximum serum concentration (tmax) [ Time Frame: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Tmax was calculated.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations

Locations
Layout table for location information
Chile
Instituto de Investigación Materno Infantil (IDIMI) - Maternidad Hospital San Borja (HCSBA)
Santiago, Chile
Sponsors and Collaborators
Laboratorios Andromaco S.A.
Investigators
Layout table for investigator information
Study Director: Grünenthal Study Director Grünenthal GmbH
Tracking Information
First Submitted Date  ICMJE May 27, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date May 30, 2019
Actual Study Start Date  ICMJE November 20, 2015
Actual Primary Completion Date July 15, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • Testosterone: Area under the serum concentration time curve (AUC0-72) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The AUC0-72 was calculated.
  • DHEA: Area under the serum concentration time curve (AUC0-72) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum DHEA were measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The AUC0-72 was calculated.
  • Testosterone: Average serum concentration 0-24 hours [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The average serum concentration achieved in the first 24 hours after administration of the assigned treatment was calculated.
  • DHEA: Average serum concentration 0-24 hours [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 24 hours ]
    Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. The average serum concentration achieved in the first 24 hours after administration of the assigned treatment was calculated.
  • Testosterone: Maximum serum concentration (Cmax) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Cmax was calculated.
  • DHEA: Maximum serum concentration (Cmax) [ Time Frame: Pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Cmax was calculated.
  • Testosterone: Time to achieve maximum serum concentration (tmax) [ Time Frame: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum testosterone was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Tmax was calculated.
  • DHEA: Time to achieve maximum serum concentration (tmax) [ Time Frame: pre-dose and from 30 minutes after administration of the assigned treatment to 72 hours ]
    Serum DHEA was measured pre-dose and at 30 minutes, at 1 hour, 2, 4, 6, 8, 24, 48, and 72 hours after vaginal ring insertion, the transdermal application of the testosterone gel, or after taking DHEA capsules. Tmax was calculated.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics of a Novel Vaginal Delivery System for Testosterone and Dehydroepiandrosterone (DHEA)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pharmacokinetics
  • Hormone Deficiency
Intervention  ICMJE
  • Drug: Dehydroepiandrosterone 2.2 g
    Vaginal ring with 2.2 grams DHEA.
  • Drug: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg
    Vaginal ring with DHEA 1.5 grams/Testosterone 25 mg.
  • Drug: Testosterone
    Vaginal ring with 35 mg testosterone.
  • Drug: Testosterone Topical Gel
    Gel containing 1% testosterone.
    Other Name: ActiserPump®
  • Drug: Dehydroepiandrosterone Oral Capsule
    Capsule containing 25 mg DHEA
Study Arms  ICMJE
  • Experimental: Group 1: AVD
    Vaginal ring with 2.2 grams dehydroepiandrosterone (DHEA), wearing time 72 hours
    Intervention: Drug: Dehydroepiandrosterone 2.2 g
  • Experimental: Group 2: AVT
    Vaginal ring with 35 mg testosterone, wearing time 72 hours.
    Intervention: Drug: Testosterone
  • Experimental: Group 3: AVD+T
    Vaginal ring with 1.5 grams DHEA and 25 mg testosterone, wearing time 72 hours.
    Intervention: Drug: Dehydroepiandrosterone 1.5 g/Testosterone 25 mg
  • Active Comparator: Group 4: DHEA capsule
    Capsules with 25 mg DHEA, oral administration every 8 hours for a 72-hour period.
    Intervention: Drug: Dehydroepiandrosterone Oral Capsule
  • Active Comparator: Group 5: Testosterone transdermal gel
    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).
    Intervention: Drug: Testosterone Topical Gel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2019)
46
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 15, 2016
Actual Primary Completion Date July 15, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 40 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03967964
Other Study ID Numbers  ICMJE PKAVD+T
EC1503 ( Other Identifier: Sponsor code )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Laboratorios Andromaco S.A.
Study Sponsor  ICMJE Laboratorios Andromaco S.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Grünenthal Study Director Grünenthal GmbH
PRS Account Laboratorios Andromaco S.A.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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