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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
Results First Posted : February 11, 2022
Last Update Posted : February 11, 2022
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Enteris BioPharma Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Endometriosis
Interventions Drug: Leuprolide Oral Tablet 4-mg QD
Drug: Leuprolide Oral Tablet 4-mg BID
Drug: Leuprolide Depot
Drug: Leuprolide Oral Tablet 10-mg BID
Enrollment 35
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Period Title: Dosing Period
Started 9 9 5 12
Completed 9 8 5 12
Not Completed 0 1 0 0
Reason Not Completed
Adverse Event             0             1             0             0
Period Title: Post- Dosing Period
Started 9 8 5 12
Completed 9 8 5 12
Not Completed 0 0 0 0
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D) Total
Hide Arm/Group Description

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Total of all reporting groups
Overall Number of Baseline Participants 9 9 5 12 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
38.4  (6.1) 38.4  (5.9) 37.8  (6.6) 37.2  (4.9) 37.9  (5.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
Female 9 9 5 12 35
Male 0 0 0 0 0
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
Hispanic or Latino
3
  33.3%
0
   0.0%
1
  20.0%
1
   8.3%
5
  14.3%
Not Hispanic or Latino
6
  66.7%
9
 100.0%
4
  80.0%
11
  91.7%
30
  85.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  11.1%
0
   0.0%
0
   0.0%
2
  16.7%
3
   8.6%
White
8
  88.9%
9
 100.0%
5
 100.0%
10
  83.3%
32
  91.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Inches
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
63.93  (2.14) 63.60  (1.10) 65.28  (2.69) 64.05  (2.15) 64.1  (2.0)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
25.734  (3.292) 26.054  (3.262) 24.242  (3.255) 24.988  (3.235) 25.3  (3.2)
Weight  
Mean (Standard Deviation)
Unit of measure:  Lbs
Number Analyzed 9 participants 9 participants 5 participants 12 participants 35 participants
149.41  (22.36) 149.63  (20.63) 147.40  (17.47) 146.64  (22.38) 148.15  (20.4)
1.Primary Outcome
Title Number of Participants With Adequacy of Suppression of Estradiol (E2) as Assessed by Estradiol Level Below 40 pg/mL
Hide Description

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.

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description:

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Overall Number of Participants Analyzed 9 8 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Days 8,15, 22, 28 and 29
6
  66.7%
7
  87.5%
5
 100.0%
12
 100.0%
Days 15, 22, 28 and 29
5
  55.6%
7
  87.5%
5
 100.0%
12
 100.0%
Days 22, 28 and 29
4
  44.4%
6
  75.0%
5
 100.0%
9
  75.0%
Days 22 and 29
4
  44.4%
6
  75.0%
5
 100.0%
9
  75.0%
Entire 28-day Dosing Period
7
  77.8%
8
 100.0%
5
 100.0%
12
 100.0%
28-day Post-dosing Period
7
  77.8%
6
  75.0%
5
 100.0%
9
  75.0%
2.Primary Outcome
Title Ovulation Rate - Measured by Number of Subjects With Progesterone Levels Not Less Than 3000 pg/mL
Hide Description

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.

Time Frame Dosing period: Day 1 to Day 28 and 28 day Post-Dosing Period; 29 day is post dosing day 1
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description:

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month (28 day cycle) of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Overall Number of Participants Analyzed 9 8 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Days 8, 15, 22, 28 and 29
4
  44.4%
3
  37.5%
3
  60.0%
10
  83.3%
Days 15, 22, 28 and 29
2
  22.2%
2
  25.0%
0
   0.0%
0
   0.0%
Days 22, 28 and 29
2
  22.2%
2
  25.0%
0
   0.0%
0
   0.0%
Days 22 and 29
2
  22.2%
1
  12.5%
0
   0.0%
0
   0.0%
Entire 28-day Dosing Period
8
  88.9%
5
  62.5%
4
  80.0%
12
 100.0%
28-day Post-dosing Period
9
 100.0%
7
  87.5%
2
  40.0%
12
 100.0%
3.Primary Outcome
Title Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAE) Excluding Menstrual Disorders
Hide Description

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.

Time Frame Dosing Period: Day 1 to day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description:

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Overall Number of Participants Analyzed 9 9 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Number of subjects with at least one TEAE
7
  77.8%
9
 100.0%
4
  80.0%
8
  66.7%
Number of subjects who discontinued due to TEAE
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs), Excluding Menstrual Disorders
Hide Description 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.
Time Frame Post dosing period (starting day 1 to day 28 post dosing period)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot(Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description:

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Overall Number of Participants Analyzed 9 8 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Number of subjects with at least one TEAE
1
  11.1%
2
  25.0%
1
  20.0%
3
  25.0%
Number of subject who discontinued due to TEAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Steady State Concentration Level, (Css) of Leuprolide
Hide Description

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).

Time Frame Treatment Day 28 for oral groups; Treatment Days 22-29 for Lupron Depot group
Hide Outcome Measure Data
Hide Analysis Population Description
Treatment D: Css determination along with most other pharmacokinetic parameters was not done for this treatment arm as fewer blood samples were planned for this treatment arm.
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description:

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

Overall Number of Participants Analyzed 8 8 5 0
Mean (Standard Deviation)
Unit of Measure: pg/mL
357.80  (367.37) 688.27  (258.01) 180.95  (101.04)
Time Frame Dosing period (day 1 to day 28) and post dosing period (day 1 to day 28)
Adverse Event Reporting Description Treatment C being a 1 month (28 day cycle) depot formulation is mentioned as a 1 month therapy but the adverse event monitoring was done for the same time frame as treatment A, B and D.
 
Arm/Group Title Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Hide Arm/Group Description

Leuprolide Oral Tablet QD: 4 mg for 28 consecutive days.

Leuprolide Oral Tablet 4-mg QD: 4-mg Leuprolide oral tablet once daily for 28 consecutive days.

Leuprolide Oral Tablet BID: 4 mg, 12 hours apart for 28 consecutive days.

Leuprolide Oral Tablet 4-mg BID: 4-mg oral tablet twice daily for 28 consecutive days.

Leuprolide Depot : intramuscular (IM) 3.75 mg depot injection administered for one month of therapy

Leuprolide Depot: 3.75 mg intramuscular depot injection

Leuprolide Oral Tablet BID: 10 mg, 12 hours apart for 28 consecutive days

Leuprolide Oral Tablet 10-mg BID: 10-mg oral tablet twice daily for 28 consecutive days.

All-Cause Mortality
Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)      0/9 (0.00%)      0/5 (0.00%)      0/12 (0.00%)    
Hide Serious Adverse Events
Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/9 (0.00%)      0/5 (0.00%)      0/12 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Leuprolide Oral Tablet, 4 mg QD (Treatment A) Leuprolide Oral Tablet, 4 mg BID (Treatment B) Leuprolide 1 Month Depot (Treatment C) Leuprolide Oral Tablet, 10 mg BID (Treatment D)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/9 (77.78%)      9/9 (100.00%)      4/5 (80.00%)      8/12 (66.67%)    
Gastrointestinal disorders         
Nausea, Vomiting, Abdominal pain, abdominal pain upper, dry mouth, faeces soft * 1  0/9 (0.00%)  0 5/9 (55.56%)  6 1/5 (20.00%)  2 2/12 (16.67%)  5
General disorders         
Axillary pain * 1  0/9 (0.00%)  0 0/9 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations         
Nasopharyngitis, gastroenteritis, vaginitis gardnerella * 1  0/9 (0.00%)  0 1/9 (11.11%)  1 1/5 (20.00%)  1 2/12 (16.67%)  2
Injury, poisoning and procedural complications         
Procedural dizziness * 1  0/9 (0.00%)  0 1/9 (11.11%)  1 0/5 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Myalgia * 1  1/9 (11.11%)  1 0/9 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders         
Headache, disturbance in attention, dizziness, presyncope * 1  4/9 (44.44%)  6 8/9 (88.89%)  10 3/5 (60.00%)  3 4/12 (33.33%)  4
Psychiatric disorders         
Depressed mood, Insomnia * 1  1/9 (11.11%)  1 0/9 (0.00%)  0 1/5 (20.00%)  1 0/12 (0.00%)  0
Reproductive system and breast disorders         
Breast tenderness. Metrorrhagia,  1  1/9 (11.11%)  1 3/9 (33.33%)  3 0/5 (0.00%)  0 4/12 (33.33%)  4
Respiratory, thoracic and mediastinal disorders         
Cough, Oropharyngeal pain * 1  1/9 (11.11%)  1 1/9 (11.11%)  1 0/5 (0.00%)  0 1/12 (8.33%)  1
Skin and subcutaneous tissue disorders         
Acne, erythema * 1  1/9 (11.11%)  1 1/9 (11.11%)  1 1/5 (20.00%)  1 1/12 (8.33%)  2
Vascular disorders         
hot flush * 1  1/9 (11.11%)  1 3/9 (33.33%)  3 1/5 (20.00%)  1 3/12 (25.00%)  4
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Paul Shields, Ph.D
Organization: Enteris Biopharma Inc.
Phone: 9734533520
EMail: pshields@enterisbiopharma.com
Layout table for additonal information
Responsible Party: Enteris BioPharma Inc.
ClinicalTrials.gov Identifier: NCT02807363    
Other Study ID Numbers: LOPDT-ENDO-01
First Submitted: June 14, 2016
First Posted: June 21, 2016
Results First Submitted: October 27, 2021
Results First Posted: February 11, 2022
Last Update Posted: February 11, 2022