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Equivalence of Intramuscular (IM) Versus Subcutaneous (SC) Applications of Long Acting Pamorelin 11.25 mg (PAMIS)

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ClinicalTrials.gov Identifier: NCT01257425
Recruitment Status : Completed
First Posted : December 9, 2010
Results First Posted : May 26, 2014
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Intervention Drug: Triptorelin Pamoate (Pamorelin® LA 11.25 mg)
Enrollment 109
Recruitment Details Patients diagnosed with advanced prostate cancer (locally advanced or metastatic, histologically proven) recruited at 23 investigational sites in Germany.
Pre-assignment Details 109 patients screened and 6 of these did not fulfil randomisation criteria therefore 103 patients were randomised to either group of treatment with triptorelin pamoate 3-month formulation applied intramuscularly or subcutaneously.
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85. Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Period Title: Overall Study
Started 52 51
Completed 46 45
Not Completed 6 6
Reason Not Completed
Lack of Efficacy             3             3
Adverse Event             1             1
Protocol Violation             1             1
Withdrawal by Subject             0             1
Death             1             0
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM. Total
Hide Arm/Group Description Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85. Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85. Total of all reporting groups
Overall Number of Baseline Participants 52 51 103
Hide Baseline Analysis Population Description
Analysed from intent-to-treat (ITT) population comprised of 103 patients (SC: 52 and IM: 51 patients).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 51 participants 103 participants
73.4  (6.7) 73.3  (7.0) 73.3  (6.8)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
50 to < 60 years 2 2 4
60 to < 70 years 10 11 21
70 to < 80 years 30 31 61
80 to < 90 years 10 7 17
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
52
 100.0%
51
 100.0%
103
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
52
 100.0%
51
 100.0%
103
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Karnofsky index (%)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
100% 21 27 48
90% 18 12 30
80% 13 12 25
[1]
Measure Description: Karnofsky index is a measure of performance status to quantify cancer patients' general well-being and activities of daily life. Karnofsky scores run from 100% (perfect health) to 0% (death). Analysed from Intent-to-treat (ITT) population comprised of 103 patients (SC:52 patients and IM:51 patients).
Prostate specific antigen (PSA) level   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 52 participants 51 participants 103 participants
47.1  (174.9) 97.2  (368.0) 71.7  (286.0)
[1]
Measure Description: Analysed from Intent-to-treat (ITT) population with one missing value in the IM group.
Testosterone serum level   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 52 participants 51 participants 103 participants
3.23  (1.28) 3.12  (1.36) 3.18  (1.31)
[1]
Measure Description: Analysed from Intent-to-treat (ITT) population comprised of 103 patients (SC:52 patients and IM:51 patients).
Tumour-related pain   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 52 participants 51 participants 103 participants
0.25  (0.58) 0.37  (0.99) 0.31  (0.81)
[1]
Measure Description: Analysed from modified ITT population comprised of 98 patients (SC: 49 and IM: 49 patients). Tumour-related pain at baseline was rated by the patient by means of a 10-cm visual analogue scale (VAS), ranging from 0 (no pain) to 10 (maximum pain).
1.Primary Outcome
Title Area Under the Curve of Testosterone Serum Concentration Between D1 and D85 (AUC1-85d).
Hide Description Area under the curve (AUC) calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 85 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.
Time Frame 1, 3, 5, 8, 15, 22, 29, 57, 85 days post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysed from ITT population.
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 52 51
Mean (Standard Deviation)
Unit of Measure: log(ng*day/mL)
4.24  (0.40) 4.23  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC., Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence margin defined as 0.8 to 1.25
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of AUC values
Estimated Value 0.977
Confidence Interval (2-Sided) 90%
0.88 to 1.08
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Area Under the Curve of Testosterone Serum Concentration Between D1 and D169 (AUC1-169d)
Hide Description Area under the curve calculated from serum testosterone concentration taken at intervals between the first administration (Day 1) of the study drug and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.
Time Frame 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 52 51
Mean (Standard Deviation)
Unit of Measure: log(ng*day/mL)
4.49  (0.42) 4.52  (0.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC., Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence margin is 0.8 to 1.25
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of AUC values
Estimated Value 0.932
Confidence Interval (2-Sided) 90%
0.82 to 1.06
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Area Under the Curve of Testosterone Serum Concentration Between D85 and D169 (AUC85-169d)
Hide Description Area under the curve calculated from serum testosterone concentration taken at intervals between Day 85 and Day 169 after dosing. From the curve describing serum testosterone concentration levels (ng/mL) over time, the AUC was calculated using numerical integration methods. This value was log-transformed to more closely meet the assumption of the statistical method.
Time Frame 85, 87, 113, 141 and 169 days post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
95 patients (IM: 47 patients, SC: 48 patients) received a second injection of the study drug.
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 48 47
Mean (Standard Deviation)
Unit of Measure: log(ng*day/mL)
2.80  (0.45) 2.88  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC., Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Equivalence margin is 0.8 to 1.25
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of AUC values
Estimated Value 0.910
Confidence Interval (2-Sided) 90%
0.81 to 1.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Maximum Concentration of Serum Testosterone [Cmax] - Raw Data
Hide Description Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169.
Time Frame 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 52 51
Mean (Standard Deviation)
Unit of Measure: ng/mL
5.74  (2.33) 5.50  (2.35)
5.Secondary Outcome
Title Maximum Concentration of Serum Testosterone [Cmax] - Log-transformed Data
Hide Description Cmax was assessed as the maximum testosterone serum concentration between the first administration of the study drug and Day 169.
Time Frame 1, 3, 5, 8, 15, 22, 29, 57, 85, 87, 113, 141 and 169 days post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 52 51
Mean (Standard Deviation)
Unit of Measure: log(ng/mL)
1.67  (0.42) 1.62  (0.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC., Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.09 to 0.11
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Castration [Tcast] - Testosterone Level Less Than or Equal to 0.5 ng/mL
Hide Description tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than or equal to 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: days
22.0
(22.0 to 23.0)
22.0
(22.0 to 23.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC., Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Time to Castration [Tcast] - Testosterone Level Less Than 0.5 ng/mL
Hide Description tcast is the number of days between day of first administration of the study drug and the day the testosterone level reaches the limit of castration defined as testosterone level less than 0.5 ng/mL for the first time. Analysis of tcast was based on the Kaplan-Meier estimator.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysed for intent-to-treat (ITT) population comprised of 103 patients (IM: 51 and SC: 52 patients).
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description:
Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: days
22.0
(22.0 to 23.0)
22.0
(22.0 to 23.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC., Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Time Frame Throughout the treatment period: 169 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Hide Arm/Group Description Subcutaneous (SC) application of triptorelin pamoate (Pamorelin LA 11.25 mg)administered on Day 1 and Day 85. Intramuscular (IM) application of triptorelin pamoate (Pamorelin LA 11.25 mg) administered on Day 1 and Day 85.
All-Cause Mortality
Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/52 (21.15%)      7/51 (13.73%)    
Cardiac disorders     
Angina pectoris * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Coronary artery disease * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Coronary artery stenosis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Gastrointestinal disorders     
Inguinal hernia * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Inguinal hernia, obstructive * 1  1/52 (1.92%)  1 1/51 (1.96%)  1
Umbilical hernia * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Vomiting * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Infections and infestations     
Bronchitis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Cellulitis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Mediastinitis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Peritonitis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Rectal abscess * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Sepsis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Urosepsis * 1  1/52 (1.92%)  1 1/51 (1.96%)  1
Injury, poisoning and procedural complications     
Subdural haematoma * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Lymphoma * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Metastasis * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Plasmacytoma * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Nervous system disorders     
Cerebrovascular accident * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Transient ischaemic attack * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Renal and urinary disorders     
Bladder outlet obstruction * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Haematuria * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Pyuria * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Renal failure * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Renal failure acute * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Urethral stenosis * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
Urinary retention * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Respiratory Failure * 1  1/52 (1.92%)  1 0/51 (0.00%)  0
Vascular disorders     
Hypertension * 1  0/52 (0.00%)  0 1/51 (1.96%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Triptorelin Pamoate (Pamorelin® LA 11.25 mg) SC. Triptorelin Pamoate (Pamorelin® LA 11.25 mg) IM.
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/52 (61.54%)      25/51 (49.02%)    
General disorders     
Fatigue * 1  0/52 (0.00%)  0 3/51 (5.88%)  3
Infections and infestations     
Urinary tract infection * 1  3/52 (5.77%)  3 3/51 (5.88%)  3
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  3/52 (5.77%)  3 1/51 (1.96%)  1
Psychiatric disorders     
Sleep disorder * 1  3/52 (5.77%)  3 0/51 (0.00%)  0
Renal and urinary disorders     
Nocturia * 1  3/52 (5.77%)  3 0/51 (0.00%)  0
Skin and subcutaneous tissue disorders     
Hyperhidrosis * 1  5/52 (9.62%)  5 4/51 (7.84%)  4
Vascular disorders     
Hot flush * 1  15/52 (28.85%)  15 14/51 (27.45%)  14
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Director, Uro-oncology
Organization: Ipsen
Phone: clinical.trials@ipsen.com
EMail: clinical.trials@ipsen.com
Layout table for additonal information
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01257425     History of Changes
Other Study ID Numbers: A-94-52014-178
2010-019632-12 ( EudraCT Number )
First Submitted: December 8, 2010
First Posted: December 9, 2010
Results First Submitted: September 27, 2013
Results First Posted: May 26, 2014
Last Update Posted: February 8, 2019