Ozono 2018 (3550‐CL‐0010).

Study characteristics
Methods	Study design: parallel‐group randomized controlled clinical trial Study dates: 2013 to 2016 Setting: multicenter, national, outpatient Country: Japan Official title: ASP3550 Phase III study ‐ an open‐label, active‐controlled, parallel‐arm study, comparing ASP3550 with goserelin acetate in patients with prostate cancer Follow‐up: 12 months
Participants	Inclusion criteria: Men, 20 years and older, with histologically confirmed prostate cancer (adenocarcinoma) Patient in whom endocrine treatment is indicated. Patient having undergoing prostatectomy or radiotherapy with curative intention and has a rising serum PSA (PSA ≥ 2 ng/mL at screening) may be included. Has a serum testosterone level above 2.2 ng/mL at screening Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2 at screening Has a serum PSA ≥ 2 ng/mL at screening Has a life expectancy of at least 12 months Exclusion criteria: Healthy volunteers Previous or present endocrine treatment for prostate cancer (e.g. surgical castration, GnRH agonists, GnRH antagonists, antiandrogens or oestrogens, and 5α‐reductase inhibitors) Received a 5α‐reductase inhibitor within 25 weeks preceding screening Is a candidate for curative therapy, i.e. radical prostatectomy or radiotherapy within 12 months Has concurrent or a history of poorly controlled severe asthma, anaphylactic reactions, severe urticaria or angioedema Has hypersensitivity towards mannitol Has a marked prolongation of QT/QTc interval (2 consecutive increases to > 450 ms in QTc interval at retest) at screening Has concurrent or a history of a disease (heart failure, hypokalemia, a family history of QT prolongation syndrome, etc.) that may induce torsade de pointes Sample size: 234 (randomized)/234 (treated) Stage of disease, n (%): localized 124 (53%); locally advanced 63 (27%); advanced (metastasized) 44 (19%); not classifiable 3 (1%)
Interventions	Group 1 (n = 117): degarelix (ASP3550) 240 mg/480 mg; an initial dose of 240 mg (40 mg/mL) degarelix was s.c. administered; after Day 28, a maintenance dose of 480 mg (60 mg/mL) was given once every 84 days. Group 2 (n = 117): goserelin (3.6 mg); an initial dose of 3.6 mg goserelin was s.c. administered; after Day 28, a maintenance dose of 10.8 mg was given once every 84 days.
Outcomes	Primary outcomes: Cumulative castration rate of treatment in terms of serum testosterone level Secondary outcomes: Proportion of castrated men in terms of serum testosterone level Changes in serum levels of PSA over time Safety assessed by the incidence of adverse events
Funding sources	Astellas Pharma Inc
Declarations of interest	Authors had industry relationships.
Notes	This study consisted of 2 parts: PART 1: ASP3550 or goserelin acetate administered for 1 year; PART 2: men assigned to receive ASP3550 and who completed the treatment in PART 1 were eligible for the treatment in PART 2, and received ASP3550 maintenance dose s.c. for long‐term safety and efficacy. We did not include data for PART 2 because of the single‐arm design. Trial ID: NCT01964170
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: “subjects were randomly allocated into a degarelix or goserelin group using a minimization method of adjusting age, cancer stage, pretreatment, and serum PSA” Comment: we assume that randomization was adequately performed.
Allocation concealment (selection bias)	Unclear risk	Quote from publication: “subjects were randomly allocated into a degarelix or goserelin group using a minimization method of adjusting age, cancer stage, pretreatment, and serum PSA” Comment: insufficient information to permit judgment.
Blinding of participants and personnel (performance bias) Subjective outcomes	High risk	Quote from publication: “open‐label, parallel‐arm study”, “For the safety analysis, the incidence of AEs, SAEs, and ADRs were collected and graded according to Common Terminology Criteria for Adverse Events version 4.0.” Comment: we judge that subjective outcomes are influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	Quote from publication: “open‐label trial”; there was no blinding of outcome assessment (or it was not reported) Comment: insufficient information to permit judgment.
Incomplete outcome data (attrition bias) Biochemical progression	Unclear risk	Comment: the study did not address this outcome.
Incomplete outcome data (attrition bias) Adverse events	Low risk	Quote from publication: “degarelix group: withdrawals 19/117 (=16.2 %); goserelin group: withdrawals 23/117 (=19.7 %)” Comment: missing outcome data are balanced in numbers across intervention groups with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Quality of life	Unclear risk	Comment: the study did not address this outcome.
Selective reporting (reporting bias)	Low risk	Comment: the study protocol is available, and all outcomes of interest have been reported.
Other bias	Low risk	Comment: we did not identify other sources of bias.