Study to Evaluate the Pharmacodynamics and Efficacy of Leuprolide Tablets (Ovarest®) in Women With Endometriosis

NCT ID: NCT05096065

Last Updated: 2022-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-18

Study Completion Date

2022-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The pharmacodynamic endpoint of percentage of subjects with suppressed estradiol level (less than 20 pg/mL) on cycle day 29 is the primary endpoint of the study.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Objectives of this study:

1. To determine efficacy and pharmacodynamic effects of various dosing regimens of Ovarest® (within the 60-mg - 120 mg daily dosing range) in women with endometriosis.
2. To determine a minimally effective daily dosing regimen of Ovarest® with pharmacodynamic effects at least comparable to the historical data for marketed Lupron Depot formulations and for GnRH antagonists indicated for the treatment of endometriosis.
3. To evaluate safety and tolerability of the long-term administration of leuprolide within the targeted daily dosing range in women with endometriosis.

The most important goal of this study is to provide adequate dose-response data for the suppression of estradiol (E2) levels below the menopausal threshold of 20 pg/mL. Results of this study in conjunction of Enteris proprietary PK data will support further development of Leuprolide Acetate Oral Tablet for the treatment of reproductive disorders, particularly endometriosis. Another reason for this trial is to support a comparative evaluation of the PD effects across the QD and BID regimens delivering the same overall dose of Ovarest

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Endometriosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment A: Leuprolide Oral Tablet, 120 mg QD

Leuprolide Oral Tablet (Ovarest), 120 mg (2 x 60 mg tablets), administered once daily (QD), for up to 35 consecutive days with food-intake restrictions.

Group Type EXPERIMENTAL

Leuprolide Oral Tablet - 120 mg - QD- Treatment A

Intervention Type DRUG

If the subject during Treatment "A" meets the pharmacodynamic success criterion (estradiol level \<20 pg/mL on Treatment Day 29 of the First Treatment Cycle), in the Second Treatment Cycle, she will be assigned Treatment "B" - 80 mg (2 x 40 mg tablets) (QD), with food-intake restrictions.

If the subject during Treatment "A" fails to meet the pharmacodynamic success criterion (i.e., if estradiol level ≥20 pg/mL on Treatment Day 29 of the First Treatment Cycle), then she will be switched to the Second Treatment Cycle with Treatment "D" - 60 mg (BID) with food intake restrictions.

Treatment B: Leuprolide Oral Tablet, 80 mg QD

Leuprolide Oral Tablet (Ovarest), 80 mg (2 x 40 mg tablets), administered once daily (QD) for up to 35 consecutive days with food-intake restrictions.

Group Type EXPERIMENTAL

Leuprolide Oral Tablet - 80 mg - QD - Treatment B

Intervention Type DRUG

If the subject on Treatment "B" meets the pharmacodynamic success criterion (estradiol level \<20 pg/mL on Treatment Day 29 of the Second Treatment Cycle), then she will be switched to the Third Treatment Cycle with Treatment "C" - 60 mg (QD) with food-intake restrictions.

If the subject on Treatment "B" does not meet the pharmacodynamic success criterion (i.e., if estradiol level ≥20 pg/mL on Treatment Day 29 of the Second Treatment Cycle), then she will be switched to the Third Treatment Cycle with Treatment "E" - 40 mg (BID) with food intake restrictions.

Treatment C: Leuprolide Oral Tablet, 60 mg QD

Leuprolide Oral Tablet (Ovarest), 60 mg, administered once daily (QD) for up to 29 consecutive days with food-intake restrictions.

Group Type EXPERIMENTAL

Leuprolide Oral Tablet - 60 mg - QD - Treatment C

Intervention Type DRUG

For up to 29 consecutive days with food-intake restrictions

Treatment D: Leuprolide Oral Tablet, 60 mg BID

Leuprolide Oral Tablet (Ovarest), 60 mg, administered twice daily (BID), 12 hours apart for up to 35 consecutive days with food-intake restrictions.

Group Type EXPERIMENTAL

Leuprolide Oral Tablet - 60 mg - BID - Treatment D

Intervention Type DRUG

If the subject on Treatment "D" fails to meet the pharmacodynamic success criterion (i.e., if estradiol level ≥20 pg/mL on Treatment Day 29 of the Second Treatment Cycle), she will be discontinued from the study following completion of the Second Treatment Cycle.

If the subject during Treatment "D" meets the pharmacodynamic success criterion (estradiol level \<20 pg/mL on Treatment Day 29 of her Second Treatment Cycle), then she will be switched to the Third Treatment Cycle with Treatment "E" - 40 mg (BID) with food intake restrictions.

Treatment E:Leuprolide Oral Tablet (Ovarest), 40 mg BID

Leuprolide Oral Tablet (Ovarest), 40 mg, administered twice daily (BID), 12 hours apart for up to 29 consecutive days with food-intake restrictions.

Group Type EXPERIMENTAL

Leuprolide Oral Tablet - 40 mg - BID - Treatment E

Intervention Type DRUG

For up to 29 consecutive days with food-intake restrictions

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Leuprolide Oral Tablet - 120 mg - QD- Treatment A

If the subject during Treatment "A" meets the pharmacodynamic success criterion (estradiol level \<20 pg/mL on Treatment Day 29 of the First Treatment Cycle), in the Second Treatment Cycle, she will be assigned Treatment "B" - 80 mg (2 x 40 mg tablets) (QD), with food-intake restrictions.

If the subject during Treatment "A" fails to meet the pharmacodynamic success criterion (i.e., if estradiol level ≥20 pg/mL on Treatment Day 29 of the First Treatment Cycle), then she will be switched to the Second Treatment Cycle with Treatment "D" - 60 mg (BID) with food intake restrictions.

Intervention Type DRUG

Leuprolide Oral Tablet - 80 mg - QD - Treatment B

If the subject on Treatment "B" meets the pharmacodynamic success criterion (estradiol level \<20 pg/mL on Treatment Day 29 of the Second Treatment Cycle), then she will be switched to the Third Treatment Cycle with Treatment "C" - 60 mg (QD) with food-intake restrictions.

If the subject on Treatment "B" does not meet the pharmacodynamic success criterion (i.e., if estradiol level ≥20 pg/mL on Treatment Day 29 of the Second Treatment Cycle), then she will be switched to the Third Treatment Cycle with Treatment "E" - 40 mg (BID) with food intake restrictions.

Intervention Type DRUG

Leuprolide Oral Tablet - 60 mg - QD - Treatment C

For up to 29 consecutive days with food-intake restrictions

Intervention Type DRUG

Leuprolide Oral Tablet - 60 mg - BID - Treatment D

If the subject on Treatment "D" fails to meet the pharmacodynamic success criterion (i.e., if estradiol level ≥20 pg/mL on Treatment Day 29 of the Second Treatment Cycle), she will be discontinued from the study following completion of the Second Treatment Cycle.

If the subject during Treatment "D" meets the pharmacodynamic success criterion (estradiol level \<20 pg/mL on Treatment Day 29 of her Second Treatment Cycle), then she will be switched to the Third Treatment Cycle with Treatment "E" - 40 mg (BID) with food intake restrictions.

Intervention Type DRUG

Leuprolide Oral Tablet - 40 mg - BID - Treatment E

For up to 29 consecutive days with food-intake restrictions

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Ovarest® 60 mg Ovarest® 40 mg Ovarest® 60 mg Ovarest® 60 mg Ovarest® 40 mg

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Women diagnosed with endometriosis and having pelvic pain, both treatment naive or previously treated with GnRH agonists or antagonists with improvement
2. Premenopausal females in general good health, including absence of current COVID infection (positive test or presence of symptoms), aged 18 to 49 years
3. BMI ≥18 and ≤35 kg/m2, and weight ≥110 lb. (≈50 kg).
4. A documented estradiol level ≥ 40 pg/mL at screening or on retest
5. Regular menstrual cycles with a usual length ranging from 21 days to 35 days. If subject has recently used hormonal birth control, historical data prior to use will be used to determine qualification and must also meet this criterion.
6. If of childbearing potential and sexually active with a risk of pregnancy, willing to use acceptable methods of contraception (Note: acceptable methods of contraception are specified in Section 8.1)
7. Willing to refrain from excessive use of alcohol during the entire study and willing to refrain from use of alcohol 24 hours prior to any PK blood draw taken during the study
8. Willing to refrain from the use of any hormone-containing or hormone-altering substances during the study.
9. Willing and able to adhere to medication schedule and to utilize the AiCure medication adherence monitoring platform correctly with the administration of each dose of medication throughout the duration of the 3 treatment cycles comprising this study
10. Willing and capable to give informed consent to participate in study

Exclusion Criteria

Subjects to whom any of the following applies will be excluded from the study:

1. Hypersensitivity to GnRH, GnRH agonist analogs, similar nonapeptides, or any of the excipients in LUPRON DEPOT. Note: This is a contraindication from the Lupron Depot label.
2. Undiagnosed abnormal vaginal bleeding. Note: This is a contraindication from the Lupron Depot label.
3. Known or suspected pregnancy, or subjects who are considering becoming pregnant prior to the conclusion of this study. Note: LUPRON DEPOT is contraindicated in women who are or may become pregnant while receiving the drug. LUPRON DEPOT may cause fetal harm when administered to a pregnant woman…. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
4. Breastfeeding or within 2 months after stopping breastfeeding (relative to the screening visit). Note: Use of LUPRON DEPOT is contraindicated in women who are breastfeeding.
5. Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions. Note: Per the LUPRON DEPOT label, a possible coadministration of norethindrone acetate is contraindicated in women with thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions.
6. Markedly impaired liver function or liver disease. Note: Per the LUPRON DEPOT label, a possible coadministration of norethindrone acetate is contraindicated in women with markedly impaired liver function or liver disease.
7. Known or suspected carcinoma of the breast. Note: Per the LUPRON DEPOT label, a possible coadministration of norethindrone acetate is contraindicated in women with known or suspected carcinoma of the breast.
8. Status postpartum or postabortion within a period of 2 months prior to the screening visit
9. History of significant alcohol or drug abuse within one year prior to the screening visit
10. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mm Hg, diastolic blood pressure lower than 50 or over 90 mm Hg, or heart rate less than 50 or over 100 bpm) at screening (following recheck after five minutes at rest)
11. Any clinically significant history or presence of neurologic, endocrinologic, pulmonary, hematologic, immunologic, or metabolic disease
12. History of severe respiratory depression or pulmonary insufficiency
13. Diabetes mellitus requiring insulin
14. History of headaches with focal neurological symptoms
15. Uncontrolled thyroid disorder
16. Sickle cell anemia
17. Current or history of clinically significant depression in the last year
18. Known disturbance of lipid metabolism
19. Hepatic adenoma or carcinoma
20. Known or suspected endometrial carcinoma or estrogen-dependent neoplasia
21. Clinically significant history or presence of any gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel diseases, history of cholecystectomy), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting) or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug
22. Difficulty in swallowing study medication
23. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in this study
24. Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening
25. Administration of any investigational drug and/or experimental device within 30 days prior to the screening visit
26. Administration of any biologics within 30 days prior to the screening visit. Note: The Covid-19 vaccine is not included in this prohibition.
27. Clinically significant finding on the ECG suggesting participation in the study could pose a risk to the subject
28. A depot injection or an implant of any drug within 1 month prior to the screening visit
29. Use of oral contraceptives or other sex steroid hormones within 1 month prior to the screening visit. Note: A 1-month drug holiday period is mandatory for potential subjects receiving GnRH agonists and GnRH antagonists.
30. Any clinically significant physical or gynecological abnormality at the screening visit
31. Any clinically significant abnormal laboratory test result at the screening visit
32. Hemoglobin \<11.5 g/dL and/or hematocrit \<32%
33. Use of over-the-counter products containing any substances which could have the propensity to impact either estradiol or gonadotropin level
34. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing
35. History of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors
36. Significant risk factors for decreased bone mineral content and/or bone mass, such as family history (in a first degree relative) of osteoporosis, personal history of chronic use of corticosteroids or anticonvulsants
37. Participation in another drug research within 1 month prior to screening
38. Deemed by the Investigator to have questionable ability to comply with the study protocol, including inadequate adherence to both dosing and use of the AiCure medication adherence monitoring platform during the Run-in Period or during the three Treatment Cycles
39. Current use of any prescription medication known to cause delayed gastric emptying (e.g. glucagon-like peptide-1 receptor agonists)
Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Parexel

INDUSTRY

Sponsor Role collaborator

Syneos Health

OTHER

Sponsor Role collaborator

Enteris BioPharma Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Gary A. Shangold, M.D.

Role: STUDY_CHAIR

Enteris BioPharma Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Physician Care Clinical Research, LLC

Sarasota, Florida, United States

Site Status RECRUITING

Complete Healthcare for Women

Columbus, Ohio, United States

Site Status RECRUITING

Tidewater Clinical Research

Norfolk, Virginia, United States

Site Status RECRUITING

Seattle Clinical Research Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Gary A. Shangold, M.D.

Role: CONTACT

862-261-9113

Sreeja Polpully Variam, M. Pharma

Role: CONTACT

9734533523

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Debbie M Hays, CCRC

Role: primary

941-954-2355

Fowzia Maniar

Role: primary

614-882-5182

April Rusch

Role: primary

757-471-3375 ext. 1

: Dominique Barragan, CCRC

Role: primary

206-522-3330 ext. 113

Shann Emerald

Role: backup

206.522.3330

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

LOPDT-ENDO-02

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.