A Study of Pharmacokinetic/Pharmacodynamic Profile of Orally Administered Leuprolide in Healthy Female Volunteers
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|ClinicalTrials.gov Identifier: NCT02807363|
Recruitment Status : Completed
First Posted : June 21, 2016
Results First Posted : February 11, 2022
Last Update Posted : February 11, 2022
|Condition or disease||Intervention/treatment||Phase|
|Endometriosis||Drug: Leuprolide Oral Tablet 4-mg QD Drug: Leuprolide Oral Tablet 4-mg BID Drug: Leuprolide Depot Drug: Leuprolide Oral Tablet 10-mg BID||Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||August 23, 2017|
|Actual Primary Completion Date :||June 27, 2018|
|Actual Study Completion Date :||June 27, 2018|
Experimental: Treatment A: Leuprolide Oral Tablet, 4 mg QD
Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.
Drug: Leuprolide Oral Tablet 4-mg QD
4-mg Leuprolide oral tablet once daily for 28 consecutive days.
Other Name: Ovarest™ 4.0 mg
Experimental: Treatment B: Leuprolide Oral Tablet, 4 mg BID
Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.
Drug: Leuprolide Oral Tablet 4-mg BID
4-mg Leuprolide oral tablet twice daily for 28 consecutive days.
Other Name: Ovarest™ 4.0 mg
Active Comparator: Treatment C: Leuprolide 1 month depot
Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy
Drug: Leuprolide Depot
3.75 mg intramuscular depot injection
Other Name: Lupron Depot® 3.75 mg
Experimental: Treatment D: Leuprolide Oral Tablet, 10 mg BID
Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days
Drug: Leuprolide Oral Tablet 10-mg BID
10-mg Leuprolide oral tablet twice daily for 28 consecutive days.
Other Name: Ovarest™ 10.0 mg
- Number of Participants With Adequacy of Suppression of Estradiol (E2) as Assessed by Estradiol Level Below 40 pg/mL [ Time Frame: Dosing Period: Day 8 to 28, Post-dosing: Day 1 to day 28 of post dosing period; Day 29 is the post dosing day 1 ]
Criterion: E2 level is considered suppressed during the evaluation period if a value below pre-specified threshold was reported at least once during that period.
The days in the row title indicate the evaluation interval.
- Ovulation Rate - Measured by Number of Subjects With Progesterone Levels Not Less Than 3000 pg/mL [ Time Frame: Dosing period: Day 1 to Day 28 and 28 day Post-Dosing Period; 29 day is post dosing day 1 ]
Progesterone level is considered suppressed during the evaluation period if a value below pre-specified threshold (3000 pg/mL) was reported at least once during that period.
The days in row title indicate the evaluation interval.
- Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAE) Excluding Menstrual Disorders [ Time Frame: Dosing Period: Day 1 to day 28 ]
The participant incidence of TEAEs was generally comparable during the dosing period across the treatment groups.
Treatment C is a depot formulation established to release the drug over a period of 1 month. The data for adverse event was collected for day 1 to 28 of the dosing period.
- Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs), Excluding Menstrual Disorders [ Time Frame: Post dosing period (starting day 1 to day 28 post dosing period) ]Treatment C is a depot formulation established to release the drug over a period of 1 month. The data for post dosing adverse event was collected starting from day 1 to 28 post the 28th day of dosing.
- Steady State Concentration Level, (Css) of Leuprolide [ Time Frame: Treatment Day 28 for oral groups; Treatment Days 22-29 for Lupron Depot group ]
Treatment A and B: Steady state concentration level calculated for oral tablets at the end of the fourth treatment week (Treatment Day 28) as the 24-hour AUCs divided by the duration of the dosing interval i.e. 24 hours.
Treatment C: Steady state concentration level calculated for IM injection at the fourth treatment week (a mean of leuprolide levels on Days 22 and 29).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02807363
|inVentiv Health Clinique, Inc.|
|Quebec City, Quebec, Canada, G1P 0A2|
|Study Chair:||Gary Shangold, MD||Enteris BioPharma Inc.|