Appendix 1. Patient disposition. PBO, placebo; UPA, ulipristal acetate; AE, adverse event; WC, withdrew consent; LFU, lost to follow-
up; PV, protocol violation; LOE, lack of efficacy.
Appendix 2. Patient global impression of improvement in menstrual bleeding after Course 1 (intent-to-treat population).
Patient-described bleeding during treatment compared with prior to treatment with study drug on a 7-point Likert scale ranging from
“very much better” to “very much worse.” UPA, ulipristal acetate; n, patients with analysis values at the specified analysis visit.
Appendix 3. Serum Levels of Markers of Bone Formation and Resorption (Safety Population)
Course 1: Course 2
Placebo:
Ulipristal 5 mg N1=42
Placebo:
Ulipristal 10 mg N1=44
Ulipristal 5 mg:
Ulipristal 5 mg N1=84
Ulipristal 5mg:
Placebo N1=40
Ulipristal 10 mg:
Ulipristal 10 mg N1=82
Ulipristal 10mg:
Placebo N1=33
Markers of Bone Formation
BSAP (µg/L) n
Baseline, mean±SD
End of Course 2,*† mean±SD
End of Study,‡ mean±SD
41
10.3±3.2
11.5±3.6
10.5±3.5
41
9.3±3.7
10.2±3.5
9.5±3.7
81
9.7±3.3
10.8±3.3
10.2±3.2
38
11.5±4.0
11.5±4.2
11.4±5.0
78
9.5±3.4
10.6±3.8
10.7±4.2
31
9.2±2.8
9.5±2.8
8.7±2.8
P1NP (ng/mL)
n
Baseline, mean±SD
End of Course 2,*§ mean±SD
41
47.1±17.1
53.2±17.9
40
50.8±20.5
60.4±31.7
81
46.2±14.2
52.0±18.3
38
51.6±19.7
56.2±27.6
78
48.4±19.6
55.4±22.7
32
45.1±16.0
49.7±29.3
End of Study,‡ mean±SD 54.0±17.9 56.5±20.2 51.8±20.0 55.6±24.7 56.2±20.5 50.4±25.6
Marker of Bone Resorption CTX (ng/L)
n
Baseline, mean±SD
End of Course 2,*|| mean±SD
End of Study,‡ mean±SD
41
312.3±130.5
335.9±126.8
328.8±150.1
39
348.1±153.8
362.7±153.5
313.5±138.3
81
311.2±123.6
322.4±151.8
305.2±152.5
38
330.9±142.1
343.0±171.0
333.6±183.1
77
299.6±162.1
343.4±168.9
303.0±135.8
32
275.1±129.7
296.3±161.5
226.5±90.3
* Samples collected at the end of the 12-week treatment period of Course 2.
† n’s at End of Course 2 were 39, 37, 76, 36, 70, and 26, respectively.
‡ Samples collected at the end of the 12-week off-treatment follow-up period following Course 2 or upon early study termination.
§ n’s at End of Course 2 were 40, 36, 76, 36, 71, and 27, respectively.
|| n’s at End of Course 2 were 37, 35, 74, 36, 69, and 26, respectively.
All BSAP and CTX values, and 97.9% of P1NP values, were within the normal ranges at baseline and end of study as defined by the central laboratory (BSAP, 3-19 μg/L; P1NP, 20-108 ng/mL; CTX, 64-640 ng/L for ages 18-29, 60-650 ng/L for ages 30-39, 40-465 ng/L for ages 40-49).
N1, patients who received ≥1 dose of study drug in Course 2; BSAP, bone specific alkaline phosphatase; n, number of patients with analysis values at both baseline and end of study; SD, standard deviation; P1NP, epitope of type I N-terminal propeptide; CTX, C-terminal telopeptide of Type I collagen.
Appendix 4. Change in Hemoglobin Levels from Baseline to End of Course 1 (Safety Population)
Course 1 Placebo
N=116
Ulipristal 5 mg N=161
Ulipristal 10 mg N=155 Hemoglobin (g/dL)
Baseline n
Mean±SD Median End of Course 1*
Mean±SD Median
98 10.6±1.9
10.7
10.9±1.9 11.0
147 11.0±1.8
11.2
11.9±1.7 12.2
133 10.5±1.7
10.4
11.7±1.7 11.8
* Samples collected at the end of the 12-week treatment period of Course 1.
Data includes only patients with analysis values at both baseline and end of Course 1.
SD, standard deviation.
Appendix 5. Progesterone Receptor Modulator
-Associated Endometrial Changes [PAEC]† (Safety Population)
Course 1Placebo N=116
Ulipristal 5 mg N=161
Ulipristal 10 mg N=155
Baseline, n1 116 160 155
PAEC, n (%) 18 (15.5) 18 (11.2) 19 (12.3)
Following 1st Menses Off-Treatment, n1
88 133 118
PAEC, n (%) 6 (6.8) 18 (13.5) 17 (14.4)
† as assessed by ≥2 of 3 independent pathologists.
n1, number of patients with non-missing diagnosis at study visit.
Appendix 6. Progesterone Receptor Modulator
-Associated Endometrial Changes [PAEC]† (Safety Population)
Course 2 (Course 1: Course 2)Placebo:
Ulipristal 5 mg N1=42
Placebo:
Ulipristal 10 mg N1=44
Ulipristal 5 mg:
Ulipristal 5 mg N1=84
Ulipristal 5mg:
Placebo N1=40
Ulipristal 10 mg:
Ulipristal 10 mg N1=82
Ulipristal 10mg:
Placebo N1=33
Baseline, n1 42 44 83 40 82 33
PAEC, n (%) 7 (16.7) 6 (13.7) 8 (9.6) 6 (15.0) 9 (11.0) 7 (21.2) Following 1st Menses
Off-Treatment, n1
34 35 66 33 61 19
PAEC, n (%) 3 (8.8) 5 (14.3) 7 (10.6) 4 (12.1) 8 (13.1) 3 (15.8)
End of Study, n1 39 37 72 38 72 25
PAEC, n (%) 5 (12.8) 4 (10.8) 5 (6.9) 4 (10.5) 10 (13.9) 1 (4.0)
