C3431003 (MDV3100-03)

Pfizer Inc.

235 E 42nd Street, New York, United States, NY 10017

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

No

No

No

Final

10 Jul 2019

No

Yes

14 Feb 2019

No

To determine the benefit of MDV3100 as compared to placebo as assessed by overall survival and by radiographic progression-free survival (rPFS).

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

28 Sep 2010

No

Yes

Australia: 232

Austria: 18

Belgium: 57

Canada: 179

Denmark: 87

Finland: 33

France: 175

Germany: 83

Israel: 25

Italy: 30

Japan: 61

Lithuania: 14

Netherlands: 28

Poland: 39

Russian Federation: 22

Singapore: 9

Slovakia: 27

Korea, Republic of: 78

Spain: 81

Sweden: 39

United Kingdom: 153

United States: 247

1717

864

0

0

0

0

0

0

358

1264

95

Double-blind

Randomised - controlled

Yes

Enzalutamide

PF-04998299

Capsule, soft

Oral use

Subjects received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.

Placebo

Capsule, soft

Oral use

Subjects received placebo, administered as four capsules, once per day by mouth.

Open-label

Non-randomised - controlled

Placebo Crossover to Enzalutamide

Capsule, soft

Oral use

Subjects who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.

Enzalutamide

Placebo

Enzalutamide

Placebo

Placebo Subjects Crossover to Enzalutamide

Overall survival was defined as the time from randomization to death due to any cause. For subjects who were alive at the time of the analysis data cutoff, overall survival was censored at the last date the subject was known to be alive or analysis data cutoff date, whichever was first. This included subjects who were known to have died after the data analysis cutoff date. Subjects with no post-baseline survival information were censored on the date of randomization. The upper limit of the 95% confidence interval was not calculable because an insufficient number of subjects reached the event at the final time point for assessment and has been denoted by '99999'. Intent to Treat (ITT) - All subjects randomly assigned to treatment.

Primary

During study period (up to 3 years)

Enzalutamide v Placebo

1717

Pre-specified

0.706

2-sided

rPFS:time from randomization to the first objective evidence of radiographic disease progression (RDP) assessed by independent central radiology review or death due to any cause within 168 days after treatment discontinuation, whichever was first. RDP was evaluated by CT scan or MRI and radionuclide bone scans at regularly scheduled visits. RDP in bone required a confirmatory scan; in soft tissue did not require a confirmatory scan for purposes of analysis. RDP was evaluated by independent central radiology review using RECIST 1.1 for soft tissue disease and PCWG2 guidelines for bone disease. ITT - All subjects randomly assigned to treatment excluding 84 subjects who were not randomized before the rPFS data cutoff date of 06 May 2012. The median time and its upper 95% confidence limit were not yet reached in the enzalutamide group because an insufficient number of subjects had an event at the time of analysis and has been denoted by '99999'.

Primary

During study period (up to 20 months)

The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.

Enzalutamide v Placebo

1633

Pre-specified

0.186

2-sided

Time to first skeletal-related event (S-RE): time from randomization to date of the first occurrence of a S-RE for each subject. S-RE: radiation therapy or surgery to bone for prostate cancer, pathological bone fracture, spinal cord compression, or initiation/change in antineoplastic therapy to treat bone pain from prostate cancer. S-REs were recorded at each scheduled and unscheduled study visit and during long-term follow-up if a S-RE was not documented previously. Subjects who did not have a S-RE at the time of analysis data cutoff were censored at the date of last assessment indicating no evidence of S-RE. Subjects with no post baseline assessments were censored on the date of randomization. Upper limit of the 95% confidence interval was not calculable because insufficient number of subjects reached the event at the final time point for assessment, has been denoted by '99999'. ITT analysis set included all randomized subjects.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

1717

Pre-specified

0.718

2-sided

The time to initiation of cytotoxic chemotherapy is defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for the treatment of prostate cancer for each subject. For subjects who did not start cytotoxic chemotherapy at the time of the analysis data cutoff, time to initiation of cytotoxic chemotherapy was censored at the date of last assessment where no cytotoxic chemotherapy was indicated or at the analysis data cutoff date, whichever was first. Time to initiation of cytotoxic chemotherapy for subjects with no postbaseline assessments was censored on the date of randomization. The upper limit of the 95% confidence interval was not calculable because an insufficient number of subjects reached the event at the final time point for assessment, and has been denoted by '99999'. ITT analysis set included all randomized subjects.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

1717

Pre-specified

0.349

2-sided

Time to PSA progression was defined as the time from randomization to date of first confirmed observation of PSA progression for each subject. For subjects with PSA declines at week 13, the PSA progression date: date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir was documented, and confirmed 3 or more weeks later. For subjects with no PSA decline at week 13, the PSA progression date: date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above baseline was documented, and confirmed 3 or more weeks later. For subjects who did not have confirmed PSA progression at the time of the analysis data cutoff, time to PSA progression was censored at the date of the last PSA assessment showing no evidence of confirmed PSA progression or the analysis data cutoff date, whichever was first. Time to PSA progression for subjects with no postbaseline assessments was censored on the date of randomization. ITT analysis set included all randomized subjects.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

1717

Pre-specified

0.169

2-sided

PSA response was defined as a >= 50% reduction in PSA from baseline to the lowest post baseline PSA value and required confirmation by a consecutive assessment at least 3 weeks later. Subjects were evaluable for PSA response rate if a subject had a PSA level measured at baseline and at least one post baseline assessment. Evaluable ITT population - All subjects randomly assigned to treatment with PSA values at baseline and at least one post baseline assessment.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

1631

Pre-specified

74.51

2-sided

The best overall soft tissue objective response is defined as partial response [PR] or complete response [CR] while on study treatment based on investigator assessments of target, nontarget, and new lesions using RECIST 1.1. Soft tissue was assessed by CT or MRI at regularly scheduled visits. Only subjects with measurable soft tissue disease (ie, at least 1 target lesion identified per RECIST 1.1) at screening are included in this analysis. All percentages are based on number of subjects with measurable soft tissue disease at screening in each treatment group. ITT population With Measurable Disease - All subjects who were randomly assigned to treatment and had at least one target lesion at screening.

Secondary

During study period (up to 3 years)

Enzalutamide v Placebo

777

Pre-specified

53.85

2-sided

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to a maximum of 6.5 years that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. The safety analysis set included all randomized subjects who received at least 1 dose or partial dose of study drug.

Other pre-specified

Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

An AE is any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =subject to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug up to a maximum duration of 6.5 years. Number of subjects with AEs of any of the Grade 3 or above (Grade 4, 5) were reported. The safety analysis set included all randomized subjects who received at least 1 dose or partial dose of study drug.

Other pre-specified

Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to a maximum duration of 6.5 years that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. The safety analysis set included all randomized subjects who received at least 1 dose or partial dose of study drug.

Other pre-specified

Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Analysis was performed on safety set.

16.1

Enzalutamide

Placebo Subjects Crossover to Enzalutamide

Placebo