A Study of Pharmacokinetic/Pharmacodynamic Profile of Orally Administered Leuprolide in Healthy Female Volunteers
Condition: Endometriosis
MeSH terms: Endometriosis
Study type: Interventional
Phase: Phase 2

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: 
      Site initiation visit of the study site, InVentiv Health Clinique, Inc. by on-site visit and
      teleconference was done and the final report signed 21st July 2017.

      For the demographic and baseline characteristics descriptive statistics consisting of mean,
      median, standard deviation, minimum, maximum and sample size is reported for continuous
      variables like age, body mass index, weight and height. categorical variables like ethnicity,
      gender and race is presented as frequency counts and percentages.

      For PK analysis, Steady state concentration level of leuprolide calculated for oral tablets
      (Treatments A and B) at the end of the fourth treatment week (Treatment Days 28) as the
      24-hour AUCs divided by the duration of the dosing interval i.e., 24 hours.

      For PD analysis, subject incidence of estradiol level below 40 pg/mL was assessed. The
      ovulation rate determined by the extent of progesterone suppression is presented.

      Only observed data is used in the data analysis except for concentration values below the
      lower limit of quantitation (BLQ) and samples with no reportable value occurring prior to
      dosing (on Day 1 only). No attempt is made to impute (i.e., extrapolate or interpolate)
      estimates for missing data.

      For safety analysis, incidence of treatment emergent adverse events both during the dosing
      and post dosing period is presented.

      The Medical Dictionary for Regulatory Activities (MedDRA®) Version 20.1 is used to classify
      all medical history findings and incidences of treatment emergent adverse events (TEAE)
      reported during the study by System Organ Class (SOC) and Preferred Term (PT).
    

Intervention name(s): Leuprolide Oral Tablet 4-mg QD; Leuprolide Oral Tablet 4-mg BID; Leuprolide Depot; Leuprolide Oral Tablet 10-mg BID
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 4-mg Leuprolide oral tablet once daily for 28 consecutive days.; 4-mg Leuprolide oral tablet twice daily for 28 consecutive days.; 3.75 mg intramuscular depot injection; 10-mg Leuprolide oral tablet twice daily for 28 consecutive days.
Other intervention name(s): Ovarest™ 4.0 mg; Ovarest™ 4.0 mg; Lupron Depot® 3.75 mg; Ovarest™ 10.0 mg
Intervention MeSH terms: Leuprolide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: endometriosis; gonadotropin-releasing hormone agonist; healthy volunteers; leuprolide oral tablet