Comparison of Pharmacokinetics of 17-Beta-Estradiol Via Sublingual Placement Versus Swallowing of 17-Beta-estradiol in Male-to-Female Transgender Patients

Sponsor

MaineHealth (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05428215

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This crossover study will investigate the pharmacokinetics of oral versus sublingual administration of 17-beta-estradiol in the trans-female population.

Condition or Disease	Intervention/Treatment	Phase
Gender Dysphoria	Drug: 17beta Estradiol	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Each subject will take their individualized dose of 17B-estradiol tablet orally for 2 weeks and sublingually for 2 weeks. The subject will then take their same dose of 17B-estradiol via the other means of administration for 2 weeks. The order in which this occurs will be randomized.Each subject will take their individualized dose of 17B-estradiol tablet orally for 2 weeks and sublingually for 2 weeks. The subject will then take their same dose of 17B-estradiol via the other means of administration for 2 weeks. The order in which this occurs will be randomized.

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Comparison of Pharmacokinetics of 17-Beta-Estradiol Via Oral Administration With Sublingual Placement Versus Oral Administration With Swallowing of 17-Beta-estradiol in Male-to-Female Transgender Patients

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PO then SL Subjects will administer 17-beta-estradiol orally (PO) for Study Day 1-14, followed by administration of 17-beta-estradiol sublingually (SL) for Study Day 15-28.	Drug: 17beta Estradiol Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration
Active Comparator: SL then PO Subjects will administer 17-beta-estradiol sublingually (SL) for Study Day 1-14, followed by administration of 17-beta-estradiol orally (PO) for Study Day 15-28.	Drug: 17beta Estradiol Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration

Arm

Intervention/Treatment

Active Comparator: PO then SL

Subjects will administer 17-beta-estradiol orally (PO) for Study Day 1-14, followed by administration of 17-beta-estradiol sublingually (SL) for Study Day 15-28.

Drug: 17beta Estradiol

Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration

Active Comparator: SL then PO

Subjects will administer 17-beta-estradiol sublingually (SL) for Study Day 1-14, followed by administration of 17-beta-estradiol orally (PO) for Study Day 15-28.

Drug: 17beta Estradiol

Subjects will take individualized therapeutic dose of 17-beta-estradiol via sublingual and oral administration

Outcome Measures

Primary Outcome Measures

Estradiol absorption [Over 24 hours]
Mean area under the curve of estradiol

Secondary Outcome Measures

Peak serum estradiol [Peak over 24 hour period]
With subjects as own controls, compare peak E2 with sublingual vs oral administration
Serum estradiol Nadir [24 hours from last estradiol administration]
Baseline serum estradiol level after 2 weeks of oral administration versus sublingual administration at same dose
Suppression of Testosterone [24 hours from last estradiol administration on Study Day 14 and 28]
Testosterone level after 2 weeks of estradiol administration via oral and sublingual method, respectively
Serum estrone to estradiol ratio [Hours from administration of estradiol: 0, 1, 2, 4, 6, and 8 hours]
E1:E2 ratio over 24 hour period with sublingual vs oral administration
Sex hormone binding globulin [0 hours from estradiol administration on Study Day 14 and 28]
SHBG after 2 weeks of estradiol sublingual vs oral administration

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

English speaker
Currently taking 17-beta-estradiol tablet daily via sublingual or oral route on dose therapeutic for gender-affirming therapy; steady dose for at least 4 weeks
Serum estradiol and testosterone levels within target therapeutic range (75-200 pg/mL and <55 ng/dL, respectively)

Exclusion Criteria:

Active or history of deep venous thrombosis/pulmonary embolism
Active or recent (within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction)
Liver dysfunction
History of breast cancer
History of orchiectomy
Known sensitivity or allergy to any components of the study medication
Taking potent CYP3A4 inhibitors or inducers