Trial Outcomes & Findings for PGL4001 Versus GnRH-agonist in Uterine Myomas (NCT NCT00740831)
NCT ID: NCT00740831
Last Updated: 2012-12-17
Results Overview
Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Patients recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Monthly scores range from 0 (amenorrhea) to more than 500, with higher numbers indicating more bleeding. A slightly stained tampon/towel scores 1, a partially stained tampon/towel scores 5, a completely saturated tampon scores 10 and a completely saturated towel scores 20. Small clots/flooding (2cm) score 1. Large clots/flooding (3cm) score 5. Menorrhagia is defined as a PBAC \> 100 during one menstrual period which approximates to a blood loss of \> 80 mL. A PBAC of 400 corresponds to a blood loss of around 300 mL or approximately 80 tampons/towels used. The week 13 PBAC score was calculated using the last 28 days of treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
301 participants
Primary outcome timeframe
3 months
Results posted on
2012-12-17
Participant Flow
Participant milestones
| Measure |
A (PGL4001 5mg)
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Overall Study
STARTED
|
97
|
103
|
101
|
|
Overall Study
COMPLETED
|
93
|
100
|
95
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
6
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PGL4001 Versus GnRH-agonist in Uterine Myomas
Baseline characteristics by cohort
| Measure |
A (PGL4001 5mg)
n=97 Participants
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=103 Participants
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=101 Participants
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
Total
n=301 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
97 Participants
n=5 Participants
|
103 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
301 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age Continuous
|
40.1 years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
40.7 years
STANDARD_DEVIATION 6.3 • n=7 Participants
|
40.3 years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
40.3 years
STANDARD_DEVIATION 6.2 • n=4 Participants
|
|
Sex: Female, Male
Female
|
97 Participants
n=5 Participants
|
103 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
301 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
Austria
|
8 participants
n=5 Participants
|
12 participants
n=7 Participants
|
8 participants
n=5 Participants
|
28 participants
n=4 Participants
|
|
Region of Enrollment
Belgium
|
12 participants
n=5 Participants
|
16 participants
n=7 Participants
|
13 participants
n=5 Participants
|
41 participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
4 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
21 participants
n=5 Participants
|
28 participants
n=7 Participants
|
18 participants
n=5 Participants
|
67 participants
n=4 Participants
|
|
Region of Enrollment
Israel
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
2 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
20 participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
42 participants
n=5 Participants
|
34 participants
n=7 Participants
|
50 participants
n=5 Participants
|
126 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: Per protocol
Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Patients recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Monthly scores range from 0 (amenorrhea) to more than 500, with higher numbers indicating more bleeding. A slightly stained tampon/towel scores 1, a partially stained tampon/towel scores 5, a completely saturated tampon scores 10 and a completely saturated towel scores 20. Small clots/flooding (2cm) score 1. Large clots/flooding (3cm) score 5. Menorrhagia is defined as a PBAC \> 100 during one menstrual period which approximates to a blood loss of \> 80 mL. A PBAC of 400 corresponds to a blood loss of around 300 mL or approximately 80 tampons/towels used. The week 13 PBAC score was calculated using the last 28 days of treatment.
Outcome measures
| Measure |
A (PGL4001 5mg)
n=93 Participants
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=95 Participants
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=92 Participants
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Percentage of Subjects With Reduction of Uterine Bleeding at Week 13 Visit Defined as Pictorial Blood-loss Assessment Chart (PBAC) Score < 75 at End-of-treatment Visit (Week 13 Visit)
|
90.3 percentage of patients
|
97.9 percentage of patients
|
89.1 percentage of patients
|
PRIMARY outcome
Timeframe: Week 13 visitPopulation: Safety population
Measured by log 10 (log pg/ml) transformed values for estradiol (E2) in blood samples
Outcome measures
| Measure |
A (PGL4001 5mg)
n=97 Participants
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=103 Participants
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=101 Participants
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Co-primary Safety Endpoint: Serum Estradiol Levels at End of Treatment Visit (Week 13 Visit) for PGL4001 Compared With GnRHagonist
|
1.897 log 10 (log pg/ml) E2
Standard Error 0.041 • Interval 45.0 to 110.0
|
1.843 log 10 (log pg/ml) E2
Standard Error 0.041 • Interval 35.0 to 121.0
|
1.381 log 10 (log pg/ml) E2
Standard Error 0.041 • Interval 10.0 to 36.0
|
PRIMARY outcome
Timeframe: Up to week 17Population: Safety population
Difference in percentage of subjects reporting moderate or severe hot flushes: Frequency and severity of this adverse event(as spontaneously reported by patients or elicited by nonleading questions) were recorded on standard forms at every visit up to week 17.
Outcome measures
| Measure |
A (PGL4001 5mg)
n=97 Participants
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=103 Participants
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=101 Participants
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Co-primary Safety Endpoint: % of Subjects Reporting Moderate or Severe Hot Flushes as Adverse Events Throughout the Treatment Period for PGL4001 Compared With GnRH-agonist
|
11.3 percentage of patients
Interval -40.6 to -14.6
|
9.7 percentage of patients
Interval -42.0 to -16.6
|
39.6 percentage of patients
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: Per protocol
Assessment of PGL4001 capacity to decrease volume of the three largest myomas was performed at each center by means of ultrasonography at baseline and at week 13. The total volume of the three largest myomas assessed at screening and at end-of-treatment visit (Week 13) was analysed on a logarithm transformed scale (to base 10).
Outcome measures
| Measure |
A (PGL4001 5mg)
n=89 Participants
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=91 Participants
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=91 Participants
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Change in the Total Volume of the Three Largest Myomas From Baseline to Week 13
|
-0.179 Log 10 (Log cm3) Total volume
Standard Error 0.037 • Interval -58.0 to -11.0
|
-0.220 Log 10 (Log cm3) Total volume
Standard Error 0.036 • Interval -69.0 to -14.0
|
-0.268 Log 10 (Log cm3) Total volume
Standard Error 0.037 • Interval -69.0 to -36.0
|
Adverse Events
A (PGL4001 5mg)
Serious events: 5 serious events
Other events: 75 other events
Deaths: 0 deaths
B (PGL4001 10mg)
Serious events: 4 serious events
Other events: 79 other events
Deaths: 0 deaths
C (GnRH-agonist)
Serious events: 4 serious events
Other events: 85 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
A (PGL4001 5mg)
n=97 participants at risk
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=103 participants at risk
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=101 participants at risk
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
1.0%
1/97 • Number of events 1
|
0.00%
0/103
|
0.00%
0/101
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
1.0%
1/97 • Number of events 1
|
0.00%
0/103
|
0.00%
0/101
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sarcoma
|
1.0%
1/97 • Number of events 1
|
0.00%
0/103
|
0.00%
0/101
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
1.0%
1/97 • Number of events 1
|
0.00%
0/103
|
0.00%
0/101
|
|
Injury, poisoning and procedural complications
Operative hemorrhage
|
1.0%
1/97 • Number of events 1
|
0.00%
0/103
|
0.00%
0/101
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leiomyoma
|
0.00%
0/97
|
0.97%
1/103 • Number of events 1
|
0.00%
0/101
|
|
Reproductive system and breast disorders
Uterine hemorrhage
|
0.00%
0/97
|
0.97%
1/103 • Number of events 1
|
0.99%
1/101 • Number of events 1
|
|
Reproductive system and breast disorders
Uterine polyp
|
0.00%
0/97
|
0.97%
1/103 • Number of events 1
|
0.00%
0/101
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hemangioma
|
0.00%
0/97
|
0.97%
1/103 • Number of events 1
|
0.00%
0/101
|
|
Infections and infestations
Lung infection
|
0.00%
0/97
|
0.00%
0/103
|
0.99%
1/101 • Number of events 1
|
|
Infections and infestations
Choriomeningitis lymphocytic
|
0.00%
0/97
|
0.00%
0/103
|
0.99%
1/101 • Number of events 1
|
|
Vascular disorders
Wound hemorrhage
|
0.00%
0/97
|
0.00%
0/103
|
0.99%
1/101 • Number of events 1
|
Other adverse events
| Measure |
A (PGL4001 5mg)
n=97 participants at risk
Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
B (PGL4001 10mg)
n=103 participants at risk
Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection)
|
C (GnRH-agonist)
n=101 participants at risk
PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection)
|
|---|---|---|---|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
40.2%
39/97 • Number of events 50
|
42.7%
44/103 • Number of events 61
|
69.3%
70/101 • Number of events 103
|
|
Reproductive system and breast disorders
Hot flush
|
25.8%
25/97 • Number of events 26
|
24.3%
25/103 • Number of events 26
|
65.3%
66/101 • Number of events 79
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
4.1%
4/97 • Number of events 6
|
4.9%
5/103 • Number of events 5
|
2.0%
2/101 • Number of events 2
|
|
Reproductive system and breast disorders
Pelvic pain
|
3.1%
3/97 • Number of events 4
|
4.9%
5/103 • Number of events 5
|
3.0%
3/101 • Number of events 3
|
|
Reproductive system and breast disorders
Ovarian cyst
|
1.0%
1/97 • Number of events 1
|
4.9%
5/103 • Number of events 5
|
2.0%
2/101 • Number of events 3
|
|
Reproductive system and breast disorders
Breast pain
|
4.1%
4/97 • Number of events 4
|
0.97%
1/103 • Number of events 1
|
2.0%
2/101 • Number of events 2
|
|
Nervous system disorders
Nervous system disorders
|
30.9%
30/97 • Number of events 47
|
26.2%
27/103 • Number of events 33
|
33.7%
34/101 • Number of events 62
|
|
Nervous system disorders
Headache
|
25.8%
25/97 • Number of events 38
|
18.4%
19/103 • Number of events 24
|
28.7%
29/101 • Number of events 49
|
|
Nervous system disorders
Migraine
|
2.1%
2/97 • Number of events 3
|
2.9%
3/103 • Number of events 3
|
3.0%
3/101 • Number of events 6
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
17.5%
17/97 • Number of events 19
|
20.4%
21/103 • Number of events 33
|
21.8%
22/101 • Number of events 35
|
|
Gastrointestinal disorders
Abdominal pain
|
3.1%
3/97 • Number of events 3
|
8.7%
9/103 • Number of events 10
|
8.9%
9/101 • Number of events 9
|
|
Gastrointestinal disorders
Nausea
|
6.2%
6/97 • Number of events 6
|
6.8%
7/103 • Number of events 7
|
5.9%
6/101 • Number of events 6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.1%
3/97 • Number of events 3
|
2.9%
3/103 • Number of events 3
|
5.0%
5/101 • Number of events 7
|
|
Gastrointestinal disorders
Diarrhoea
|
2.1%
2/97 • Number of events 2
|
1.9%
2/103 • Number of events 2
|
3.0%
3/101 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
3.1%
3/97 • Number of events 3
|
1.9%
2/103 • Number of events 2
|
0.99%
1/101 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
1.0%
1/97 • Number of events 1
|
0.97%
1/103 • Number of events 1
|
4.0%
4/101 • Number of events 4
|
|
Infections and infestations
Infections and infestations
|
14.4%
14/97 • Number of events 20
|
15.5%
16/103 • Number of events 19
|
15.8%
16/101 • Number of events 23
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
6/97 • Number of events 6
|
3.9%
4/103 • Number of events 4
|
2.0%
2/101 • Number of events 2
|
|
Infections and infestations
Influenza
|
2.1%
2/97 • Number of events 2
|
1.9%
2/103 • Number of events 2
|
5.0%
5/101 • Number of events 5
|
|
Infections and infestations
Pharyngitis
|
5.2%
5/97 • Number of events 5
|
0.00%
0/103
|
2.0%
2/101 • Number of events 2
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/97
|
1.9%
2/103 • Number of events 2
|
3.0%
3/101 • Number of events 3
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
12.4%
12/97 • Number of events 13
|
16.5%
17/103 • Number of events 18
|
11.9%
12/101 • Number of events 15
|
|
Injury, poisoning and procedural complications
Procedural pain
|
9.3%
9/97 • Number of events 10
|
14.6%
15/103 • Number of events 15
|
8.9%
9/101 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
8.2%
8/97 • Number of events 10
|
12.6%
13/103 • Number of events 15
|
9.9%
10/101 • Number of events 15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.1%
4/97 • Number of events 4
|
2.9%
3/103 • Number of events 3
|
4.0%
4/101 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.1%
2/97 • Number of events 2
|
3.9%
4/103 • Number of events 4
|
3.0%
3/101 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.1%
2/97 • Number of events 2
|
1.9%
2/103 • Number of events 2
|
3.0%
3/101 • Number of events 3
|
|
General disorders
General disorders and administration site conditions
|
7.2%
7/97 • Number of events 7
|
16.5%
17/103 • Number of events 21
|
8.9%
9/101 • Number of events 11
|
|
General disorders
Fatigue
|
4.1%
4/97 • Number of events 4
|
6.8%
7/103 • Number of events 8
|
3.0%
3/101 • Number of events 3
|
|
General disorders
Asthenia
|
0.00%
0/97
|
3.9%
4/103 • Number of events 4
|
0.99%
1/101 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
5.2%
5/97 • Number of events 5
|
10.7%
11/103 • Number of events 12
|
12.9%
13/101 • Number of events 14
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/97
|
4.9%
5/103 • Number of events 6
|
5.0%
5/101 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.0%
1/97 • Number of events 1
|
0.00%
0/103
|
3.0%
3/101 • Number of events 3
|
|
Psychiatric disorders
Psychiatric disorders
|
4.1%
4/97 • Number of events 5
|
3.9%
4/103 • Number of events 6
|
12.9%
13/101 • Number of events 15
|
|
Psychiatric disorders
Insomnia
|
2.1%
2/97 • Number of events 2
|
1.9%
2/103 • Number of events 2
|
5.0%
5/101 • Number of events 5
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
6.2%
6/97 • Number of events 6
|
2.9%
3/103 • Number of events 3
|
5.0%
5/101 • Number of events 5
|
|
Blood and lymphatic system disorders
Anemia
|
5.2%
5/97 • Number of events 5
|
2.9%
3/103 • Number of events 3
|
5.0%
5/101 • Number of events 5
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
6.2%
6/97 • Number of events 6
|
2.9%
3/103 • Number of events 3
|
4.0%
4/101 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypercholesterolemia
|
4.1%
4/97 • Number of events 4
|
0.97%
1/103 • Number of events 1
|
0.99%
1/101 • Number of events 1
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders
|
4.1%
4/97 • Number of events 4
|
4.9%
5/103 • Number of events 5
|
3.0%
3/101 • Number of events 3
|
|
Ear and labyrinth disorders
Vertigo
|
4.1%
4/97 • Number of events 4
|
4.9%
5/103 • Number of events 5
|
3.0%
3/101 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place