Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Pharmacokinetic/Pharmacodynamic Profile of Orally Administered Leuprolide in Healthy Female Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02807363
Recruitment Status : Completed
First Posted : June 21, 2016
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Enteris BioPharma Inc.

Tracking Information
First Submitted Date  ICMJE June 14, 2016
First Posted Date  ICMJE June 21, 2016
Last Update Posted Date June 19, 2018
Actual Study Start Date  ICMJE August 23, 2017
Actual Primary Completion Date June 18, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2016)
Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 40 pg/mL [ Time Frame: Treatment day 22 to day 29 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2016)
  • Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 40 pg/mL [ Time Frame: Treatment Day 1 to Day 15; Post-Dosing Day 7 to Day 28 ]
  • Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 20 pg/mL [ Time Frame: Treatment Day 1 to Day 29; Post-Dosing Day 7 to Day 28 ]
  • Adequacy of suppression of ovulation as assessed by the subject incidence of progesterone level below 3 ng /mL [ Time Frame: Treatment Day 1 to Day 29; Post-Dosing Day 7 to Day 28 ]
  • Adequacy of suppression of menstrual periods as assessed by the number of vaginal (menstrual) bleeding days [ Time Frame: : Treatment Day 1 to Day 29; Post-Dosing Day 7 to Day 28 ]
  • Serum concentration, AUC (area under curve) of Leuprolide [ Time Frame: Treatment Days 1 and 28 ]
  • Serum concentration, Css (steady state levels) of Leuprolide [ Time Frame: Treatment Days 28-29 for oral groups; Treatment Days 22-29 for Lupron Depot group ]
  • Number of patients with adverse events [ Time Frame: Treatment Day 1 to Day 29; Post-Dosing Day 1 to Day 28 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2016)
  • Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 40 pg/mL [ Time Frame: Treatment Day 1 to Day 15; Post-Dosing Day 7 to Day 28 ]
  • Adequacy of suppression of estradiol (E2) as assessed by the subject incidence of estradiol level below 20 pg/mL [ Time Frame: Treatment Day 1 to Day 29; Post-Dosing Day 7 to Day 28 ]
  • Adequacy of suppression of ovulation as assessed by the subject incidence of progesterone level below 3 ng /mL [ Time Frame: Treatment Day 1 to Day 29; Post-Dosing Day 7 to Day 28 ]
  • Adequacy of suppression of menstrual periods as assessed by the number of vaginal (menstrual) bleeding days [ Time Frame: : Treatment Day 1 to Day 29; Post-Dosing Day 7 to Day 28 ]
  • Serum concentration, AUC (area under curve) of Leuprolide Acetate [ Time Frame: Treatment Days 1 and 28 ]
  • Serum concentration, Css (steady state levels) of Leuprolide Acetate [ Time Frame: Treatment Days 28-29 for oral groups; Treatment Days 22-29 for Lupron Depot group ]
  • Number of patients with adverse events [ Time Frame: Treatment Day 1 to Day 29; Post-Dosing Day 1 to Day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Pharmacokinetic/Pharmacodynamic Profile of Orally Administered Leuprolide in Healthy Female Volunteers
Official Title  ICMJE A Randomized, Open-label, Parallel-group, Active-control PK/PD Study of Three Doses of Leuprolide Oral Tablets in Comparison to an IM Dose of Leuprolide in Healthy Female Volunteers
Brief Summary This Phase 2a, pharmacokinetic/pharmacodynamic study will determine the safety and provide evaluation of the PK/PD metrics of three different oral doses selected upon the results of the study LOPDT-PH1-01 - 4 mg oral tablets administered over 28 days as QD and BID regimens and 10 mg oral tablets administered over 28 days as a BID regimen. The PK/PD profiles of the study drug will be compared to the leuprolide formulation approved for the treatment of endometriosis (a monthly intramuscular injection, Lupron Depot 3.75 mg). Major PK (e.g., a total exposure to leuprolide) and PD parameters (e.g., rates of the estradiol suppression and cessation of the menstrual period) will also be evaluated against the Lupron Depot historical data.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Endometriosis
Intervention  ICMJE
  • Drug: Leuprolide Oral Tablet 4-mg QD
    4-mg oral tablet once daily for 28 consecutive days.
  • Drug: Leuprolide Oral Tablet 4-mg BID
    4-mg oral tablet twice daily for 28 consecutive days.
  • Drug: Leuprolide Depot
    3.75 mg intramuscular depot injection
    Other Name: Lupron
  • Drug: Leuprolide Oral Tablet 10-mg BID
    10-mg oral tablet twice daily for 28 consecutive days.
Study Arms  ICMJE
  • Experimental: Leuprolide Oral Tablet, 4 mg QD
    Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.
    Intervention: Drug: Leuprolide Oral Tablet 4-mg QD
  • Experimental: Leuprolide Oral Tablet, 4 mg BID
    Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.
    Intervention: Drug: Leuprolide Oral Tablet 4-mg BID
  • Active Comparator: Leuprolide 1 month depot
    Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy
    Intervention: Drug: Leuprolide Depot
  • Experimental: Leuprolide Oral Tablet, 10 mg BID
    Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days
    Intervention: Drug: Leuprolide Oral Tablet 10-mg BID
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: June 16, 2016)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 18, 2018
Actual Primary Completion Date June 18, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy premenopausal female volunteers, aged 18 to 49 years
  2. Body mass index (BMI) ≥18 and ≤ 32 kg/m2, and weight ≥ 110 lbs. (≈50 kg).
  3. 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.
  4. If of childbearing potential and sexually active with a risk of pregnancy, willing to use one of the following acceptable methods of contraception throughout the study and for at least 30 days after the last drug administration:

    1. intra-uterine contraceptive device without hormone release system placed at least 4 weeks prior to the first study drug administration with simultaneous use of condom for the male partner
    2. simultaneous use of diaphragm with intravaginally applied spermicide and condom for the male partner
    3. sterile male partner (vasectomized for at least 6 months);
  5. 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
  6. Willing to refrain from use of prescription medications, over-the-counter medications and natural health products during the entire study
  7. Willing and capable

Exclusion Criteria:

  1. Hypersensitivity to GnRH, GnRH agonist analogs 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 This is a contraindication from the Lupron Depot label
  4. Breast-feeding or within 2 months after stopping breast-feeding (relative to the screening visit) Note: Use of LUPRON DEPOT is contraindicated in women who are breast-feeding.
  5. Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions. Note: Per the LUPRON DEPOT label, a possible co-administration 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 co-administration of Norethindrone acetate is contraindicated in women with markedly impaired liver function or liver disease.
  7. Known or suspected carcinoma of the breast. Per the LUPRON DEPOT label, a possible co-administration of Norethindrone acetate is contraindicated in women with known or suspected carcinoma of the breast.
  8. Status post-partum or post-abortion within a period of 2 months prior to the screening visit
  9. A cervical cytology smear of Papanicolaou (Pap) class III or greater or a Bethesda System report of low grade squamous intraepithelial lesions (SIL) or greater (PAP smear results within last 12 months are acceptable if properly documented)
  10. Use of any tobacco products (including electronic cigarettes) in the 3 months preceding the screening visit or positive urine cotinine test at screening.
  11. History of significant alcohol or drug abuse within one year prior to the screening visit.
  12. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening.
  13. Any clinically significant history or presence of neurologic, endocrinologic, pulmonary, hematologic, immunologic, or metabolic disease
  14. History of severe respiratory depression or pulmonary insufficiency.
  15. Diabetes Mellitus requiring insulin
  16. History of headaches with focal neurological symptoms
  17. Uncontrolled thyroid disorder
  18. Sickle cell anemia
  19. Current or history of clinically significant depression in the last year
  20. Known disturbance of lipid metabolism
  21. Hepatic adenoma or carcinoma
  22. Undiagnosed abnormal genital bleeding
  23. Known or suspected endometrial carcinoma, or estrogen-dependent neoplasia
  24. History of sensitivity to leuprolide acetate or other GnRH agonists
  25. Clinically significant history or presence of any gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), 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.
  26. Difficulty in swallowing study medication
  27. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in this study
  28. Positive test for hepatitis B, hepatitis C, or HIV at screening
  29. Administration of any investigational drug and/or experimental device within 30 days prior to the screening visit
  30. Administration of any biologics within 90 days prior to the screening visit
  31. Clinically significant finding on the ECG suggesting participation in the study could pose a risk to the subject
  32. A depot injection or an implant of any drug within 6 months prior to the screening visit
  33. Use of oral contraceptives or other sex steroid hormones within 3 months prior to the screening visit
  34. Any clinically significant physical or gynecological abnormality at the screening visit
  35. Any clinically significant abnormal laboratory test result at the screening visit
  36. Hemoglobin <115 g/L and/or hematocrit < 0.32 L/L
  37. Use of prescription medication within 14 days prior to the first administration of study medication or over-the-counter products (including natural health products, e.g. food supplements, vitamins, herbal supplements) within 7 days prior to the first administration of study medication, except for topical products without significant systemic absorption
  38. 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
  39. Deemed by the Investigator to have questionable ability to comply with the study protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 49 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02807363
Other Study ID Numbers  ICMJE LOPDT-ENDO-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Enteris BioPharma Inc.
Study Sponsor  ICMJE Enteris BioPharma Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Enteris BioPharma Inc.
Verification Date June 2018

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