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

NCT05096065 | Unknown Phase 2 FDA Drug

• 1 other identifier: LOPDT-ENDO-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Endometriosis

Keywords

Leuprolide oral tablets; Endometriosis; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 20 pg/mL

  The primary PD metric - suppression of E2 level (E2 \<20 pg/mL) - will be assessed at each on-treatment evaluation timepoint. E2 below 20 pg/mL at Day 29 is a primary endpoint for a given Treatment Cycle.

  Treatment cycle: Day 29

Secondary Outcomes (6)

• Suppression of ovulation (as evidenced by progesterone levels <3 ng/mL)

  Treatment cycle: Day 22 and 29

• Number of vaginal (menstrual) bleeding days

  28 days of therapy and 14 days post study follow up

• Composite Pelvic Signs and Symptoms (CPSS) scores

  Treatment day 29

• (Pre-dose leuprolide level) Subject incidence of Leuprolide below detectable level

  Treatment Cycle: Days 1, 8, 15, 22 and 29 days

• Luteinizing hormone (LH) levels

  Treatment days: 1,8, 15, 22 and 29; Post dosing day 14

Study Arms (5)

Treatment A: Leuprolide Oral Tablet, 120 mg QD

EXPERIMENTAL

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.

Drug: Leuprolide Oral Tablet - 120 mg - QD- Treatment A

Treatment B: Leuprolide Oral Tablet, 80 mg QD

EXPERIMENTAL

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.

Drug: Leuprolide Oral Tablet - 80 mg - QD - Treatment B

Treatment C: Leuprolide Oral Tablet, 60 mg QD

EXPERIMENTAL

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

Drug: Leuprolide Oral Tablet - 60 mg - QD - Treatment C

Treatment D: Leuprolide Oral Tablet, 60 mg BID

EXPERIMENTAL

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

Drug: Leuprolide Oral Tablet - 60 mg - BID - Treatment D

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

EXPERIMENTAL

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

Drug: Leuprolide Oral Tablet - 40 mg - BID - Treatment E

Interventions

Leuprolide Oral Tablet - 120 mg - QD- Treatment A 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.

Also known as: Ovarest® 60 mg

Treatment A: Leuprolide Oral Tablet, 120 mg QD

Leuprolide Oral Tablet - 80 mg - QD - Treatment B 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.

Also known as: Ovarest® 40 mg

Treatment B: Leuprolide Oral Tablet, 80 mg QD

Leuprolide Oral Tablet - 60 mg - QD - Treatment C DRUG

For up to 29 consecutive days with food-intake restrictions

Also known as: Ovarest® 60 mg

Treatment C: Leuprolide Oral Tablet, 60 mg QD

Leuprolide Oral Tablet - 60 mg - BID - Treatment D 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.

Also known as: Ovarest® 60 mg

Treatment D: Leuprolide Oral Tablet, 60 mg BID

Leuprolide Oral Tablet - 40 mg - BID - Treatment E DRUG

For up to 29 consecutive days with food-intake restrictions

Also known as: Ovarest® 40 mg

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

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: Females, aged 18 to 49 years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women diagnosed with endometriosis and having pelvic pain, both treatment naive or previously treated with GnRH agonists or antagonists with improvement
• Premenopausal females in general good health, including absence of current COVID infection (positive test or presence of symptoms), aged 18 to 49 years
• BMI ≥18 and ≤35 kg/m2, and weight ≥110 lb. (≈50 kg).
• A documented estradiol level ≥ 40 pg/mL at screening or on retest
• 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.
• 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)
• 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
• Willing to refrain from the use of any hormone-containing or hormone-altering substances during the study.
• 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
• Willing and capable to give informed consent to participate in study

You may not qualify if:

• Subjects to whom any of the following applies will be excluded from the study:
• 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.
• Undiagnosed abnormal vaginal bleeding. Note: This is a contraindication from the Lupron Depot label.
• 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.
• 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.
• 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.
• 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.
• 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.
• Status postpartum or postabortion within a period of 2 months prior to the screening visit
• History of significant alcohol or drug abuse within one year prior to the screening visit
• 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)
• Any clinically significant history or presence of neurologic, endocrinologic, pulmonary, hematologic, immunologic, or metabolic disease
• History of severe respiratory depression or pulmonary insufficiency
• Diabetes mellitus requiring insulin
• History of headaches with focal neurological symptoms

Sponsors & Collaborators

• Enteris BioPharma Inc.: lead
• Parexel: collaborator
• Syneos Health: collaborator

Study Sites (4)

Physician Care Clinical Research, LLC

Sarasota, Florida, 34239, United States

RECRUITING

Complete Healthcare for Women

Columbus, Ohio, 43231, United States

RECRUITING

Tidewater Clinical Research

Norfolk, Virginia, 23502, United States

RECRUITING

Seattle Clinical Research Center

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Endometriosis

Interventions

Leuprolide

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Gary A. Shangold, M.D.

  Enteris BioPharma Inc.

  STUDY CHAIR

Central Study Contacts

Gary A. Shangold, M.D.

CONTACT

862-261-9113; gshangold@enterisbiopharma.com

Sreeja Polpully Variam, M. Pharma

CONTACT

9734533523; svariam@enterisbiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: October 27, 2021
• Study Start: March 18, 2022
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: March 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)