Trial Outcomes & Findings for A Phase 3 Comparative Study of TAP-144-SR(6M) in Prostate Cancer Patients Previously Treated With Hormonal Therapy (NCT NCT01546623)

NCT ID: NCT01546623

Last Updated: 2015-07-21

Results Overview

Comparison of the proportion of patients maintained at castration level (≤100 ng/dL)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

160 participants

Primary outcome timeframe

From the start of study drug administration through Week 48

Results posted on

2015-07-21

Participant Flow

Participants took part in the study at 23 investigative sites in Japan from 11 April 2012 to 04 April 2014.

Prostate cancer patients previously treated with hormonal therapy were enrolled in 1 of 2 treatment groups. Two patients withdrew from the period between randomization and starting study drugs (1 in TAP-144-SR(6M) arm and 1 in TAP-144-SR(3M) arm).

Participant milestones

Participant milestones
Measure	TAP-144-SR(6M) TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Overall Study STARTED	82	80
Overall Study Received Study Drug	81	79
Overall Study COMPLETED	76	74
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	TAP-144-SR(6M) TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Overall Study Adverse Event	2	3
Overall Study Major Protocol Deviation	1	1
Overall Study High Prostate specific antigen	2	1
Overall Study Did Not Receive Study Drug	1	1

Baseline Characteristics

A Phase 3 Comparative Study of TAP-144-SR(6M) in Prostate Cancer Patients Previously Treated With Hormonal Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAP-144-SR(6M) n=82 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=80 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.	Total n=162 Participants Total of all reporting groups
Age, Continuous	73.3 Years STANDARD_DEVIATION 6.32 • n=5 Participants	72.6 Years STANDARD_DEVIATION 6.49 • n=7 Participants	73.0 Years STANDARD_DEVIATION 6.39 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants	80 Participants n=7 Participants	162 Participants n=5 Participants
Weight	64.03 kg STANDARD_DEVIATION 8.689 • n=5 Participants	65.83 kg STANDARD_DEVIATION 8.098 • n=7 Participants	64.92 kg STANDARD_DEVIATION 8.424 • n=5 Participants
Body Mass Index (BMI)	23.61 kg/m^2 STANDARD_DEVIATION 2.731 • n=5 Participants	24.32 kg/m^2 STANDARD_DEVIATION 2.769 • n=7 Participants	23.96 kg/m^2 STANDARD_DEVIATION 2.764 • n=5 Participants
Gleason Score 2	0 Participants 0.0 • n=5 Participants	0 Participants 0.0 • n=7 Participants	0 Participants n=5 Participants
Gleason Score 3	0 Participants 0.0 • n=5 Participants	0 Participants 0.0 • n=7 Participants	0 Participants n=5 Participants
Gleason Score 4	0 Participants 0.0 • n=5 Participants	0 Participants 0.0 • n=7 Participants	0 Participants n=5 Participants
Gleason Score 5	2 Participants 2.4 • n=5 Participants	2 Participants 2.5 • n=7 Participants	4 Participants n=5 Participants
Gleason Score 6	8 Participants 9.8 • n=5 Participants	7 Participants 8.8 • n=7 Participants	15 Participants n=5 Participants
Gleason Score 7	35 Participants 42.7 • n=5 Participants	29 Participants 36.3 • n=7 Participants	64 Participants n=5 Participants
Gleason Score 8	14 Participants 17.1 • n=5 Participants	21 Participants 26.3 • n=7 Participants	35 Participants n=5 Participants
Gleason Score 9	20 Participants 24.4 • n=5 Participants	21 Participants 26.3 • n=7 Participants	41 Participants n=5 Participants
Gleason Score 10	3 Participants 3.7 • n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T T0	0 Participants 0.0 • n=5 Participants	0 Participants 0.0 • n=7 Participants	0 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T T1	17 Participants 20.7 • n=5 Participants	16 Participants 20.3 • n=7 Participants	33 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T T2	32 Participants 39.0 • n=5 Participants	24 Participants 30.4 • n=7 Participants	56 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T T3	29 Participants 35.4 • n=5 Participants	33 Participants 41.8 • n=7 Participants	62 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T T4	4 Participants 4.9 • n=5 Participants	6 Participants 7.6 • n=7 Participants	10 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T TX	0 Participants 0.0 • n=5 Participants	0 Participants 0.0 • n=7 Participants	0 Participants n=5 Participants
Tumor-node-metastasis (TNM) classification at diagnosis: T Unknown	0 Participants 0 • n=5 Participants	0 Participants 0.0 • n=7 Participants	0 Participants n=5 Participants
TNM classification at diagnosis: N N0	69 Participant n=5 Participants	62 Participant n=7 Participants	131 Participant n=5 Participants
TNM classification at diagnosis: N N1	13 Participant n=5 Participants	17 Participant n=7 Participants	30 Participant n=5 Participants
TNM classification at diagnosis: N NX	0 Participant n=5 Participants	0 Participant n=7 Participants	0 Participant n=5 Participants
TNM classification at diagnosis: N Unknown	0 Participant n=5 Participants	0 Participant n=7 Participants	0 Participant n=5 Participants
TNM classification at diagnosis: M M0	63 participants n=5 Participants	62 participants n=7 Participants	125 participants n=5 Participants
TNM classification at diagnosis: M M1	19 participants n=5 Participants	17 participants n=7 Participants	36 participants n=5 Participants
TNM classification at diagnosis: M Unknown	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Period between date of first dianosis and date of informed consent	1.653 Years STANDARD_DEVIATION 2.0866 • n=5 Participants	1.748 Years STANDARD_DEVIATION 2.0410 • n=7 Participants	1.700 Years STANDARD_DEVIATION 2.0583 • n=5 Participants
Period between first dose dates of leuproride acetate (over-the-counter) and the study drug	46.328 Weeks STANDARD_DEVIATION 20.0833 • n=5 Participants	46.595 Weeks STANDARD_DEVIATION 20.8584 • n=7 Participants	46.460 Weeks STANDARD_DEVIATION 20.4056 • n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	73 Participants n=5 Participants	71 Participants n=7 Participants	144 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of study drug administration through Week 48

Population: Full analysis set participants (all randomized participants who received at least 1 dose of study drug) was used.

Comparison of the proportion of patients maintained at castration level (≤100 ng/dL)

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
The Rate of Suppression of Serum Testosterone to Castrate Level Number of participants maintained	81 Participants	78 Participants
The Rate of Suppression of Serum Testosterone to Castrate Level Number of participants who did not maintain	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From baseline to Week 48

Population: Full analysis set participants (all randomized participants who received at least 1 dose of open-label study drug) with both Baseline and a post-baseline value; last observation carried forward was used.

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Time Course of Changes in Serum Testosterone Baseline	8.0 ng/dL Interval 0.0 to 33.0	7.0 ng/dL Interval 0.0 to 388.0
Time Course of Changes in Serum Testosterone Week 1	6.0 ng/dL Interval 0.0 to 33.0	7.0 ng/dL Interval 0.0 to 267.0
Time Course of Changes in Serum Testosterone Week 2	7.0 ng/dL Interval 0.0 to 37.0	6.0 ng/dL Interval 0.0 to 55.0
Time Course of Changes in Serum Testosterone Week 4	7.0 ng/dL Interval 0.0 to 35.0	8.0 ng/dL Interval 0.0 to 33.0
Time Course of Changes in Serum Testosterone Week 8	7.5 ng/dL Interval 0.0 to 53.0	8.0 ng/dL Interval 0.0 to 33.0
Time Course of Changes in Serum Testosterone Week 12	7.0 ng/dL Interval 0.0 to 41.0	8.0 ng/dL Interval 0.0 to 36.0
Time Course of Changes in Serum Testosterone Week 16	7.0 ng/dL Interval 0.0 to 45.0	7.5 ng/dL Interval 0.0 to 34.0
Time Course of Changes in Serum Testosterone Week 20	8.0 ng/dL Interval 0.0 to 43.0	6.0 ng/dL Interval 0.0 to 40.0
Time Course of Changes in Serum Testosterone Week 24	7.0 ng/dL Interval 0.0 to 37.0	6.0 ng/dL Interval 0.0 to 33.0
Time Course of Changes in Serum Testosterone Week 25	6.0 ng/dL Interval 0.0 to 30.0	5.5 ng/dL Interval 0.0 to 30.0
Time Course of Changes in Serum Testosterone Week 26	5.0 ng/dL Interval 0.0 to 35.0	4.0 ng/dL Interval 0.0 to 32.0
Time Course of Changes in Serum Testosterone Week 28	8.0 ng/dL Interval 0.0 to 36.0	6.0 ng/dL Interval 0.0 to 36.0
Time Course of Changes in Serum Testosterone Week 32	9.0 ng/dL Interval 0.0 to 41.0	8.0 ng/dL Interval 0.0 to 30.0
Time Course of Changes in Serum Testosterone Week 36	8.0 ng/dL Interval 0.0 to 34.0	7.0 ng/dL Interval 0.0 to 40.0
Time Course of Changes in Serum Testosterone Week 40	8.0 ng/dL Interval 0.0 to 39.0	8.0 ng/dL Interval 0.0 to 37.0
Time Course of Changes in Serum Testosterone Week 44	7.0 ng/dL Interval 0.0 to 37.0	8.0 ng/dL Interval 0.0 to 33.0
Time Course of Changes in Serum Testosterone Week 48	9.0 ng/dL Interval 0.0 to 42.0	6.0 ng/dL Interval 0.0 to 34.0

SECONDARY outcome

Timeframe: From baseline to Week 48

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Time Course of Changes in Serum Luteinizing Hormone (LH) Baseline	0.000 mIU/mL Interval 0.0 to 1.44	0.000 mIU/mL Interval 0.0 to 12.25
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 1	0.160 mIU/mL Interval 0.0 to 1.03	0.220 mIU/mL Interval 0.0 to 7.57
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 2	0.180 mIU/mL Interval 0.0 to 0.68	0.150 mIU/mL Interval 0.0 to 2.91
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 4	0.120 mIU/mL Interval 0.0 to 0.37	0.110 mIU/mL Interval 0.0 to 0.65
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 8	0.000 mIU/mL Interval 0.0 to 0.33	0.000 mIU/mL Interval 0.0 to 0.67
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 12	0.000 mIU/mL Interval 0.0 to 0.35	0.110 mIU/mL Interval 0.0 to 1.56
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 16	0.000 mIU/mL Interval 0.0 to 0.38	0.055 mIU/mL Interval 0.0 to 0.87
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 20	0.000 mIU/mL Interval 0.0 to 0.36	0.110 mIU/mL Interval 0.0 to 0.58
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 24	0.000 mIU/mL Interval 0.0 to 1.38	0.000 mIU/mL Interval 0.0 to 0.63
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 25	0.150 mIU/mL Interval 0.0 to 0.67	0.185 mIU/mL Interval 0.0 to 0.54
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 26	0.170 mIU/mL Interval 0.0 to 0.84	0.130 mIU/mL Interval 0.0 to 0.48
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 28	0.110 mIU/mL Interval 0.0 to 0.35	0.000 mIU/mL Interval 0.0 to 0.59
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 32	0.000 mIU/mL Interval 0.0 to 0.26	0.000 mIU/mL Interval 0.0 to 0.66
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 36	0.000 mIU/mL Interval 0.0 to 0.24	0.000 mIU/mL Interval 0.0 to 0.76
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 40	0.000 mIU/mL Interval 0.0 to 0.31	0.000 mIU/mL Interval 0.0 to 0.49
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 44	0.000 mIU/mL Interval 0.0 to 0.32	0.000 mIU/mL Interval 0.0 to 0.66
Time Course of Changes in Serum Luteinizing Hormone (LH) Week 48	0.000 mIU/mL Interval 0.0 to 0.42	0.000 mIU/mL Interval 0.0 to 0.84

SECONDARY outcome

Timeframe: From baseline to Week 48

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 26	5.010 mIU/mL Interval 2.34 to 13.14	5.020 mIU/mL Interval 1.96 to 14.69
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Baseline	5.120 mIU/mL Interval 1.93 to 13.31	4.780 mIU/mL Interval 2.02 to 18.52
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 1	5.430 mIU/mL Interval 1.87 to 15.52	4.810 mIU/mL Interval 1.77 to 17.62
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 2	4.890 mIU/mL Interval 1.99 to 13.12	4.710 mIU/mL Interval 1.81 to 16.4
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 4	4.625 mIU/mL Interval 1.72 to 14.11	4.950 mIU/mL Interval 1.49 to 16.19
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 8	5.225 mIU/mL Interval 1.9 to 13.75	5.240 mIU/mL Interval 1.79 to 17.23
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 12	5.340 mIU/mL Interval 2.24 to 14.04	5.110 mIU/mL Interval 1.86 to 15.97
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 16	5.300 mIU/mL Interval 2.07 to 13.87	5.370 mIU/mL Interval 1.81 to 15.65
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 20	5.030 mIU/mL Interval 1.65 to 12.21	5.260 mIU/mL Interval 1.91 to 15.01
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 24	4.990 mIU/mL Interval 1.97 to 13.45	5.150 mIU/mL Interval 2.12 to 16.47
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 25	5.210 mIU/mL Interval 2.16 to 12.92	4.970 mIU/mL Interval 1.84 to 17.02
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 28	5.060 mIU/mL Interval 2.31 to 13.38	5.070 mIU/mL Interval 2.05 to 13.63
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 32	5.210 mIU/mL Interval 2.32 to 13.2	5.030 mIU/mL Interval 2.08 to 12.54
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 36	5.585 mIU/mL Interval 2.01 to 13.0	4.970 mIU/mL Interval 2.09 to 14.08
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 40	5.100 mIU/mL Interval 1.8 to 14.85	4.910 mIU/mL Interval 2.05 to 13.2
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 44	5.150 mIU/mL Interval 1.69 to 12.9	4.990 mIU/mL Interval 2.17 to 14.14
Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) Week 48	5.110 mIU/mL Interval 1.44 to 11.69	4.820 mIU/mL Interval 2.18 to 14.46

SECONDARY outcome

Timeframe: From baseline to Week 48

Evaluation according to the "Criteria for therapeutic effect" from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition (determination of therapeutic effect by prostate-specific antigen \[PSA\])

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Time Course of Change Rate in Serum PSA (FAS) Week 20	-44.740 percent change Interval -100.0 to 932.65	-39.970 percent change Interval -100.0 to 3718.18
Time Course of Change Rate in Serum PSA (FAS) Week 24	-49.270 percent change Interval -100.0 to 2002.04	-31.110 percent change Interval -100.0 to 9900.0
Time Course of Change Rate in Serum PSA (FAS) Week 28	-56.705 percent change Interval -100.0 to 2920.41	-45.875 percent change Interval -100.0 to 15354.55
Time Course of Change Rate in Serum PSA (FAS) Week 32	-57.690 percent change Interval -100.0 to 7389.8	-40.745 percent change Interval -100.0 to 21051.52
Time Course of Change Rate in Serum PSA (FAS) Week 36	-60.710 percent change Interval -100.0 to 9675.51	-50.520 percent change Interval -100.0 to 23506.06
Time Course of Change Rate in Serum PSA (FAS) Week 40	-80.610 percent change Interval -100.0 to 5348.98	-58.520 percent change Interval -100.0 to 21627.27
Time Course of Change Rate in Serum PSA (FAS) Week44	-74.105 percent change Interval -100.0 to 6859.18	-54.585 percent change Interval -100.0 to 24506.06
Time Course of Change Rate in Serum PSA (FAS) Week 48	-72.900 percent change Interval -100.0 to 6818.37	-59.400 percent change Interval -100.0 to 22839.39
Time Course of Change Rate in Serum PSA (FAS) Week 4	-7.930 percent change Interval -100.0 to 181.82	-10.000 percent change Interval -100.0 to 122.95
Time Course of Change Rate in Serum PSA (FAS) Week 8	-14.255 percent change Interval -100.0 to 190.06	-15.880 percent change Interval -100.0 to 184.85
Time Course of Change Rate in Serum PSA (FAS) Week 12	-20.810 percent change Interval -100.0 to 360.84	-21.130 percent change Interval -100.0 to 754.55
Time Course of Change Rate in Serum PSA (FAS) Week 16	-19.720 percent change Interval -100.0 to 634.69	-20.650 percent change Interval -100.0 to 1866.67

SECONDARY outcome

Timeframe: From baseline to Week 48

Evaluation according to the "Criteria for therapeutic effect" from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition (determination of therapeutic effect by PSA)

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=54 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=55 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
The Maximum Rate of Change in PSA Suppression (FAS)	-86.225 percent change Interval -100.0 to 108.73	-67.030 percent change Interval -100.0 to 75.76

SECONDARY outcome

Timeframe: From baseline to Week 48

Evaluation according to the "Criteria for therapeutic effect" from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition (determination of therapeutic effect by PSA)

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=80 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=77 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Percentage of Participants With Progression by PSA (FAS) Presence of disesase progression: Yes	7.5 percentage of participants	92.5 percentage of participants
Percentage of Participants With Progression by PSA (FAS) Presence of disesase progression: No	6.5 percentage of participants	93.5 percentage of participants

SECONDARY outcome

Timeframe: At week 48

Assessment in accordance with the "criteria for therapeutic effect" from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition. Soft tissue response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=79 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=76 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Soft Tissue Response Complete response	0.0 Percentage of participants	0.0 Percentage of participants
Soft Tissue Response Partial Response	0.0 Percentage of participants	0.0 Percentage of participants
Soft Tissue Response Stable Disease	13.9 Percentage of participants	11.8 Percentage of participants
Soft Tissue Response Progressive Disease	0.0 Percentage of participants	2.6 Percentage of participants
Soft Tissue Response Not Evaluable	86.1 Percentage of participants	85.5 Percentage of participants

SECONDARY outcome

Timeframe: At Week 48

Partially revised assessment based on the "criteria for therapeutic effect" from the General Rule for Clinical and Pathological Studies on Prostate Canter, 4th edition. Response is measured using bone scintigraphy. Increase in new (2 or more) bone lesion is considered as progression

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=78 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=75 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Bone Lesion Response Presence of disesase progression: New lesions ≥ 2	1.3 Percentage of participants	1.3 Percentage of participants
Bone Lesion Response Presence of disesase progression: New lesions < 1	98.7 Percentage of participants	98.7 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to Week 48

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Serum Unchanged TAP-144 Level Baseline	0.07113 ng/dL Standard Deviation 0.043808	0.06188 ng/dL Standard Deviation 0.035339
Serum Unchanged TAP-144 Level Week 1	0.1304 ng/dL Standard Deviation 0.16388	0.1869 ng/dL Standard Deviation 0.077198
Serum Unchanged TAP-144 Level Week 2	0.3085 ng/dL Standard Deviation 0.30523	0.1335 ng/dL Standard Deviation 0.083060
Serum Unchanged TAP-144 Level Week 4	0.8845 ng/dL Standard Deviation 0.52695	0.1132 ng/dL Standard Deviation 0.12110
Serum Unchanged TAP-144 Level Week 8	0.1792 ng/dL Standard Deviation 0.10354	0.08374 ng/dL Standard Deviation 0.041078
Serum Unchanged TAP-144 Level Week 12	0.1256 ng/dL Standard Deviation 0.068860	0.08039 ng/dL Standard Deviation 0.056305
Serum Unchanged TAP-144 Level Week 16	0.1024 ng/dL Standard Deviation 0.093951	0.1220 ng/dL Standard Deviation 0.067137
Serum Unchanged TAP-144 Level Week 20	0.06957 ng/dL Standard Deviation 0.053682	0.08450 ng/dL Standard Deviation 0.039532
Serum Unchanged TAP-144 Level Week 24	0.05167 ng/dL Standard Deviation 0.043221	0.07437 ng/dL Standard Deviation 0.045186
Serum Unchanged TAP-144 Level Week 25	0.1353 ng/dL Standard Deviation 0.29809	0.1978 ng/dL Standard Deviation 0.083286
Serum Unchanged TAP-144 Level Week 26	0.4318 ng/dL Standard Deviation 0.63101	0.1418 ng/dL Standard Deviation 0.087312
Serum Unchanged TAP-144 Level Week 28	0.7622 ng/dL Standard Deviation 0.42483	0.1067 ng/dL Standard Deviation 0.054505
Serum Unchanged TAP-144 Level Week 32	0.1524 ng/dL Standard Deviation 0.098308	0.08236 ng/dL Standard Deviation 0.046180
Serum Unchanged TAP-144 Level Week 36	0.1091 ng/dL Standard Deviation 0.057582	0.08407 ng/dL Standard Deviation 0.075147
Serum Unchanged TAP-144 Level Week 40	0.09118 ng/dL Standard Deviation 0.065771	0.1086 ng/dL Standard Deviation 0.051455
Serum Unchanged TAP-144 Level Week 44	0.06958 ng/dL Standard Deviation 0.055624	0.08639 ng/dL Standard Deviation 0.051923
Serum Unchanged TAP-144 Level Week 48	0.04596 ng/dL Standard Deviation 0.030006	0.07945 ng/dL Standard Deviation 0.066980

SECONDARY outcome

Timeframe: At 1 hour, week 24, and week 48 after administration

Population: Safety evaluation was conducted in the safety analysis set (SAS), which includes all 160 patients who received the study drug \[TAP-144-SR (\&M) group: 81 patients, TAP-144-SR (3M) group: 79 patients

Outcome measures

Outcome measures
Measure	TAP-144-SR(6M) n=81 Participants TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 Participants TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
12-lead ECG QTcF interval measurement at Basline	429.0 msec Standard Deviation 15.75	436.2 msec Standard Deviation 15.63
12-lead ECG QTcF interval measurement at 1 hour	422.2 msec Standard Deviation 20.80	432.2 msec Standard Deviation 21.93
12-lead ECG QTcF interval measurement at Week 24	425.0 msec Standard Deviation 20.01	433.4 msec Standard Deviation 18.91
12-lead ECG QTcF interval measurement at Week 48	428.1 msec Standard Deviation 16.42	431.7 msec Standard Deviation 16.05

Adverse Events

TAP-144-SR(6M)

Serious events: 10 serious events

Other events: 74 other events

Deaths: 0 deaths

TAP-144-SR(3M)

Serious events: 8 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Measure	TAP-144-SR(6M) n=81 participants at risk TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 participants at risk TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
Injury, poisoning and procedural complications Femur fracture	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Inguinal hernia	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Large intestine polyp	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic gastric cancer	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary infarction	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dementia with Lewy bodies	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral infarction	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Loss of consciousness	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Calculus bladder	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Appendicitis perforated	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Disuse syndrome	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Cataract	0.00% 0/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Measure	TAP-144-SR(6M) n=81 participants at risk TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks.	TAP-144-SR(3M) n=79 participants at risk TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks.
General disorders Injection site induration	17.3% 14/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.9% 11/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	3.7% 3/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 5/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dental caries	7.4% 6/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Injection site erythema	14.8% 12/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.6% 6/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Injection site pain	7.4% 6/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 5/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	22.2% 18/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	31.6% 25/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	7.4% 6/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 3/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Contusion	7.4% 6/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 1/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatine phosphokinase increased	6.2% 5/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.9% 7/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Weight increased	1.2% 1/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 5/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Diabetes mellitus	6.2% 5/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.5% 2/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 5/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 5/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	2.5% 2/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.1% 8/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	2.5% 2/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.1% 4/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	3.7% 3/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 5/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hot flush	6.2% 5/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 5/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	6.2% 5/81 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.8% 3/79 • From the first dose of study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open-label study drug (up to 56 weeks). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.