SPARTAN: A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer

Sponsor
Aragon Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01946204
Collaborator
(none)
1,207
391
2
109.5
3.1
0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of apalutamide in adult men with high-risk non-metastatic castration-resistant prostate cancer.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This Phase 3 clinical trial is an essential step in the evaluation of an investigational medication to see if it may be useful in treating prostate cancer. The purpose of the SPARTAN study is to compare the safety and effectiveness of the investigational medication to placebo in delaying prostate cancer from spreading to other parts of the body. A placebo is a pill that looks like the investigational medication but does not contain any active medication, a dummy pill.

Phase 3 studies are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in previous Phase 2 studies. These studies are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug.

Study participants will take the oral investigational medication daily. One cycle of study treatment lasts 4 weeks or 28 days. The number of cycles will depend on how you and your cancer respond to the study medication.

In order for the researchers to evaluate and compare the study results, there are two different study groups. Study participants will be randomly (like flipping a coin) assigned to one of these groups:

  • One group will receive their current treatment along with the investigational medication

  • One group will receive their current medications along with a placebo

The investigational medication will be given to 2 out of every 3 study participants. Neither you nor the study staff will know which group you are in. However, in case of a medical emergency, your study doctor can quickly find out which treatment group you are in.

All participants will continue to receive their current treatment along with either the investigational medication or a placebo. The selections will be random, and you may remain on investigational treatment until your disease worsens, or until significant side effects occur or you can no longer tolerate treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
1207 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer
Actual Study Start Date :
Oct 14, 2013
Actual Primary Completion Date :
May 19, 2017
Anticipated Study Completion Date :
Nov 29, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Arm A: Apalutamide

Drug: Apalutamide
240 mg tablets administered by mouth on a continuous once daily dosing regimen

Placebo Comparator: Treatment Arm B: Placebo

Drug: Placebo
Matched placebo tablets administered by mouth on a continuous once daily dosing regimen

Outcome Measures

Primary Outcome Measures

  1. Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR) [Up to approximately 43 Months]

    MFS was defined as the time from randomization to the time of first evidence of BICR-confirmed bone or soft tissue distant metastasis or death due to any cause, whichever occurred first. The MFS data for participants without metastasis or death were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and computerized tomography [CT] or magnetic resonance imaging [MRI] of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.

Secondary Outcome Measures

  1. Time to Metastasis (TTM) [Up to approximately 43 Months]

    Time to metastasis (TTM) was defined as the time from randomization to the time of the scan that showed first evidence of BICR-confirmed radiographically detected bone or soft tissue distant metastasis. The TTM data for participants without metastasis were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and CT or MRI of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.

  2. Progression-free Survival (PFS) [Up to approximately 43 Months]

    PFS defined as time from randomization to first documentation of BICR-confirmed radiographic progressive disease (PD) (development of distant/local/regional metastasis)/death due to any cause whichever occurred first. PFS data for participants without loco-regional disease were performed for US/ex-US regulatory purposes. Radiographic scans (bone scans and CT/MRI of chest,abdomen,pelvis) performed for detection of metastasis throughout study. PD based on RECIST v1.1; Subjects with one measurable lesion, At least 20% increase in sum of diameters of target lesions taking as reference smallest sum on study. In addition, sum must demonstrate an absolute increase of at least 5 millimeter(mm). Also, appearance of one/more new lesions was also considered PD. Subjects with non-measurable disease as per CT/MRI scans, unequivocal progression/appearance of one or more new lesions was considered PD. For new bone lesions detected on bone scans, second imaging (CT/MRI) was required to confirm PD.

  3. Time to Symptomatic Progression [Up to approximately 43 Months]

    Time to symptomatic progression was defined as the time from randomization to documentation in the CRF of any of the following (whichever occurred earlier): a) development of a skeletal-related event (pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone); b) pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy; or c) development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy.

  4. Overall Survival [Up to approximately 43 months]

    Overall survival was defined as the time from randomization to the date of death due to any cause.

  5. Time to Initiation of Cytotoxic Chemotherapy [Up to approximately 43 months]

    Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equal to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous ADT (androgen deprivation therapy)

  • Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises, at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)

  • Maintain castrate levels of testosterone within 4 weeks prior to randomization and throughout the study

  • Patients currently receiving bone loss prevention treatment with bone-sparing agents must be on stable doses for at least 4 weeks prior to randomization

  • Patients who received a first generation anti-androgen (for example, bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washout

  • At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors, estrogens, and any other anti-cancer therapy prior to randomization

  • At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization

  • Eastern Cooperative Oncology Group Performance Status 0 or 1

  • Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade <= 1 or baseline prior to randomization

  • Adequate organ function according to protocol-defined criteria

  • Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility

Exclusion Criteria:
  • Presence of confirmed distant metastases, including central nervous system and vertebral or meningeal involvement

  • Symptomatic local or regional disease requiring medical intervention

  • Prior treatment with second generation anti-androgens

  • Prior treatment with CYP17 inhibitors

  • Prior treatment with radiopharmaceutical agents, or any other investigational agent for non-metastatic castration-resistant prostate cancer

  • Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting

  • History of seizure or condition that may pre-dispose to seizure

  • Concurrent therapy with protocol-defined excluded medications

  • History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months prior to randomization; uncontrolled hypertension; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures

Contacts and Locations

Locations

Site City State Country Postal Code
1 Birmingham Alabama United States
2 Anchorage Alaska United States
3 Chandler Arizona United States
4 Tucson Arizona United States
5 Duarte California United States
6 Fullerton California United States
7 Laguna Woods California United States
8 Los Angeles California United States
9 Orange California United States
10 Roseville California United States
11 Sacramento California United States
12 San Bernardino California United States
13 San Diego California United States
14 San Francisco California United States
15 Santa Monica California United States
16 Sherman Oaks California United States
17 Stanford California United States
18 Tarzana California United States
19 Torrance California United States
20 Denver Colorado United States
21 Englewood Colorado United States
22 Glenwood Springs Colorado United States
23 Grand Junction Colorado United States
24 Washington District of Columbia United States
25 Aventura Florida United States
26 Boca Raton Florida United States
27 Bradenton Florida United States
28 Daytona Beach Florida United States
29 Fort Myers Florida United States
30 Hialeah Florida United States
31 Jacksonville Florida United States
32 Miami Florida United States
33 New Port Richey Florida United States
34 Orlando Florida United States
35 Saint Petersburg Florida United States
36 Sarasota Florida United States
37 Wellington Florida United States
38 Meridian Idaho United States
39 Chicago Illinois United States
40 Decatur Illinois United States
41 Maywood Illinois United States
42 Melrose Park Illinois United States
43 Carmel Indiana United States
44 Jeffersonville Indiana United States
45 Muncie Indiana United States
46 West Des Moines Iowa United States
47 Westwood Kansas United States
48 Wichita Kansas United States
49 Metairie Louisiana United States
50 New Orleans Louisiana United States
51 Annapolis Maryland United States
52 Baltimore Maryland United States
53 Rockville Maryland United States
54 Towson Maryland United States
55 Boston Massachusetts United States
56 Detroit Michigan United States
57 Lansing Michigan United States
58 Minneapolis Michigan United States
59 Royal Oak Michigan United States
60 Duluth Minnesota United States
61 Bay Saint Louis Mississippi United States
62 Southaven Mississippi United States
63 Kansas City Missouri United States
64 Missoula Montana United States
65 Omaha Nebraska United States
66 Las Vegas Nevada United States
67 Hooksett New Hampshire United States
68 Hackensack New Jersey United States
69 Lawrenceville New Jersey United States
70 Morristown New Jersey United States
71 Mount Laurel New Jersey United States
72 New Brunswick New Jersey United States
73 Voorhees New Jersey United States
74 Albuquerque New Mexico United States
75 Albany New York United States
76 Bronx New York United States
77 Mineola New York United States
78 New York New York United States
79 Oneida New York United States
80 Poughkeepsie New York United States
81 Syracuse New York United States
82 Concord North Carolina United States
83 Greensboro North Carolina United States
84 Greenville North Carolina United States
85 Salisbury North Carolina United States
86 Winston-Salem North Carolina United States
87 Cincinnati Ohio United States
88 Cleveland Ohio United States
89 Middleburg Heights Ohio United States
90 Middletown Ohio United States
91 Bend Oregon United States
92 Portland Oregon United States
93 Tualatin Oregon United States
94 Bala-Cynwyd Pennsylvania United States
95 Bryn Mawr Pennsylvania United States
96 Lancaster Pennsylvania United States
97 Philadelphia Pennsylvania United States
98 Pittsburgh Pennsylvania United States
99 Warwick Rhode Island United States
100 Charleston South Carolina United States
101 Greenville South Carolina United States
102 Myrtle Beach South Carolina United States
103 West Columbia South Carolina United States
104 Memphis Tennessee United States
105 Nashville Tennessee United States
106 Abilene Texas United States
107 Amarillo Texas United States
108 Dallas Texas United States
109 Fort Sam Houston Texas United States
110 Houston Texas United States
111 McAllen Texas United States
112 San Antonio Texas United States
113 Norfolk Virginia United States
114 Richmond Virginia United States
115 Virginia Beach Virginia United States
116 Burien Washington United States
117 Edmonds Washington United States
118 Seattle Washington United States
119 Tacoma Washington United States
120 Green Bay Wisconsin United States
121 Madison Wisconsin United States
122 Milwaukee Wisconsin United States
123 Adelaide Australia
124 Box Hill Australia
125 Camperdown Australia
126 Darlinghurst Australia
127 Geelong Australia
128 Gosford Australia
129 Hobart Australia
130 Kogarah Australia
131 Liverpool Australia
132 Melbourne Australia
133 Nedlands Australia
134 Parkville Australia
135 South Woodville Australia
136 Southport Australia
137 Sydney Australia
138 Tweed Heads Australia
139 Wollongong Australia
140 Graz Austria
141 Innsbruck Austria
142 Linz Austria
143 Vienna Austria
144 Brussels Belgium
145 Brussel Belgium
146 Gent Belgium
147 Kortrijk Belgium
148 Leuven Belgium
149 Liege Belgium
150 Ottignies Belgium
151 Calgary Alberta Canada
152 Edmonton Alberta Canada
153 Abbotsford British Columbia Canada
154 Vancouver British Columbia Canada
155 Victoria British Columbia Canada
156 Moncton New Brunswick Canada
157 Saint John New Brunswick Canada
158 Halifax Nova Scotia Canada
159 Barrie Ontario Canada
160 Brampton Ontario Canada
161 Brantford Ontario Canada
162 Hamilton Ontario Canada
163 London Ontario Canada
164 North York Ontario Canada
165 Oakville Ontario Canada
166 Ottawa Ontario Canada
167 Owen Sound Ontario Canada
168 Toronto Ontario Canada
169 Gatineau Quebec Canada
170 Granby Quebec Canada
171 Greenfield Park Quebec Canada
172 Laval Quebec Canada
173 Montreal Quebec Canada
174 Pointe-Claire Quebec Canada
175 Sherbrooke Quebec Canada
176 Kelowna Canada
177 Montrel Canada
178 Quebec Canada
179 Toronto Canada
180 Liberec Czechia
181 Olomouc Czechia
182 Opava Czechia
183 Plzen Czechia
184 Praha 2 Czechia
185 Praha 4 Czechia
186 Praha 5 Czechia
187 Praha Czechia
188 Aalborg C Denmark
189 Copenhagen Denmark
190 Odense N/a Denmark
191 Roskilde Denmark
192 Helsinki Finland
193 Oulu Finland
194 Seinäjoki Finland
195 Tampere Finland
196 Turku Finland
197 Angers Cedex 9 France
198 Angers France
199 Besancon France
200 Bordeaux France
201 Caen Cédex 05 France
202 Clermont Ferrand France
203 Hyers France
204 La Roche sur Yon Cedex 9 France
205 Le Mans France
206 Lille Cedex N/a France
207 Lyon France
208 Marseille cedex 5 France
209 Marseille Cedex 9 France
210 Nice Cedex 2 France
211 Nîmes Cedex 9 France
212 Paris 75 France
213 Paris Cedex 15 France
214 Paris France
215 Reims Cedex France
216 Rennes Cedex France
217 Rouen France
218 Saint Gregoire France
219 Saint Herblain France
220 Strasbourg France
221 Suresnes France
222 Tours, Cedex 9 France
223 Vandoeuvre Les Nancy Cedex France
224 Aachen Germany
225 Bergisch Gladbach Germany
226 Berlin Germany
227 Braunschweig Germany
228 Duisburg Germany
229 Emmendingen Germany
230 Frankfurt / Main Germany
231 Greifswald Germany
232 Göttingen Germany
233 Hamburg Germany
234 Hannover Germany
235 Heidelberg Germany
236 Heinsberg Germany
237 Homburg/Saar Germany
238 Jena Germany
239 Kiel Germany
240 Kirchheim unter Teck Germany
241 Köln Germany
242 Magdeburg Germany
243 Mainz Germany
244 Mannheim Germany
245 Marburg Germany
246 Mettmann Germany
247 Müllheim Germany
248 Münster Germany
249 Nuertingen Germany
250 Regensburg Germany
251 Rostock Germany
252 Tübingen Germany
253 Weiden Germany
254 Wilhelmshaven Germany
255 Wuppertan Germany
256 Zirndorf Germany
257 Budapest Hungary
258 Miskolc Hungary
259 Nyíregyhá Hungary
260 Sopron Hungary
261 Szentes Hungary
262 Haifa Israel
263 Jeruselem Israel
264 Kfar-Saba Israel
265 Petah-Tikva Israel
266 Ramat Gan Israel
267 Tel Aviv Israel
268 Zerifin Israel
269 Akita Japan
270 Fukuoka-shi Japan
271 Gifu Japan
272 Hakodate Japan
273 Hiroshima Japan
274 Hokkaido Japan
275 Kanazawa Japan
276 Kashiwa Japan
277 Kita-Gun Japan
278 Kobe Japan
279 Koshigaya Japan
280 Kumamoto Japan
281 Kurume Japan
282 Matsuyama Japan
283 Nagano Japan
284 Nagasaki Japan
285 Nagoya Japan
286 Niigata Japan
287 Osaka-Sayama Japan
288 Osaka Japan
289 Sagamihara Japan
290 Sakura Japan
291 Sapporo Japan
292 Shinjuku-Ku Japan
293 Tokushima Japan
294 Tokyo Japan
295 Ube Japan
296 Wakayama Japan
297 Yokohama Japan
298 Daegu Korea, Republic of
299 Gwangju-si Korea, Republic of
300 Pusan Korea, Republic of
301 Seongnam Korea, Republic of
302 Seoul Korea, Republic of
303 Alkmaar Netherlands
304 Eindhoven Netherlands
305 Hoofddorp Netherlands
306 Leidschendam Netherlands
307 Nijmegen Netherlands
308 Rotterdam Netherlands
309 Auckland New Zealand
310 Christchurch New Zealand
311 Hamilton New Zealand
312 Nelson City New Zealand
313 Tauranga New Zealand
314 Whangarei New Zealand
315 Nordbyhagen Norway
316 Bialystok Poland
317 Bydgoszcz Poland
318 Gdansk Poland
319 Kutno Poland
320 Lodz Poland
321 Poznan Poland
322 Szczecin Poland
323 Torun Poland
324 Warszawa Poland
325 Wroclaw Poland
326 Baia Mare Romania
327 Brasov Romania
328 Bucharest Romania
329 Cluj- Napoca Romania
330 Targu Mures Romania
331 Barnaul Russian Federation
332 Ekaterinburg Russian Federation
333 Ivanovo Russian Federation
334 Moscow Russian Federation
335 Obninsk, Kaluga Region Russian Federation
336 Omsk Russian Federation
337 Ryazan Russian Federation
338 Saint Petersburg Russian Federation
339 St. Petersburg Russian Federation
340 Ufa Russian Federation
341 Yaroslavl Russian Federation
342 Banska Bystrica Slovakia
343 Bratislava Slovakia
344 Martin Slovakia
345 Nitra Slovakia
346 Trenčín Slovakia
347 Badalona Spain
348 Barcelona Spain
349 Castellon Spain
350 Coruña Spain
351 Girona Spain
352 Guadalajara Spain
353 Jerez de la Frontera Spain
354 Las Palmas De Gran Canaria Spain
355 Madrid Spain
356 Murcia Spain
357 Málaga Spain
358 Palma de Mallorca Spain
359 Pamplona Spain
360 Sabadell Spain
361 Salamanca Spain
362 San Sebastian de los Reyes Spain
363 Santander Spain
364 Sevilla N/a Spain
365 Sevilla Spain
366 Valencia Spain
367 Goteborg Sweden
368 Stockholm Sweden
369 Umea Sweden
370 Uppsala Sweden
371 Örebro Sweden
372 Kaohsiung Taiwan
373 Taichung Taiwan
374 Taipei Taiwan
375 Taoyuan County Taiwan
376 Blackburn United Kingdom
377 Cambridge United Kingdom
378 Cardiff United Kingdom
379 Dundee United Kingdom
380 Glasgow United Kingdom
381 Guildford United Kingdom
382 Leeds United Kingdom
383 London United Kingdom
384 Maidstone United Kingdom
385 Nottingham United Kingdom
386 Plymouth United Kingdom
387 Southampton United Kingdom
388 Surrey United Kingdom
389 Swansea United Kingdom
390 Wirral United Kingdom
391 Wolverhampton United Kingdom

Sponsors and Collaborators

  • Aragon Pharmaceuticals, Inc.

Investigators

  • Study Director: Aragon Pharmaceuticals, Inc. Clinical Trial, Aragon Pharmaceuticals, Inc.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01946204
Other Study ID Numbers:
  • CR102931
  • ARN-509-003
  • 2012-004322-24
First Posted:
Sep 19, 2013
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Aragon Pharmaceuticals, Inc.
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Period Title: Overall Study
STARTED 401 806
Treated 398 803
COMPLETED 0 0
NOT COMPLETED 401 806

Baseline Characteristics

Arm/Group Title Placebo Apalutamide Total
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Total of all reporting groups
Overall Participants 401 806 1207
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
74.1
(7.92)
73.7
(8.07)
73.9
(8.02)
Sex: Female, Male (Count of Participants)
Female
0
0%
0
0%
0
0%
Male
401
100%
806
100%
1207
100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
5
1.2%
11
1.4%
16
1.3%
Not Hispanic or Latino
338
84.3%
659
81.8%
997
82.6%
Unknown or Not Reported
58
14.5%
136
16.9%
194
16.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
4
0.5%
4
0.3%
Asian
47
11.7%
93
11.5%
140
11.6%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
20
5%
48
6%
68
5.6%
White
276
68.8%
524
65%
800
66.3%
More than one race
0
0%
1
0.1%
1
0.1%
Unknown or Not Reported
58
14.5%
136
16.9%
194
16.1%
Region of Enrollment (Count of Participants)
Australia
11
2.7%
30
3.7%
41
3.4%
Austria
2
0.5%
4
0.5%
6
0.5%
Belgium
3
0.7%
4
0.5%
7
0.6%
Canada
21
5.2%
61
7.6%
82
6.8%
Czech Republic
14
3.5%
20
2.5%
34
2.8%
Denmark
7
1.7%
14
1.7%
21
1.7%
Finland
5
1.2%
7
0.9%
12
1%
France
21
5.2%
39
4.8%
60
5%
Germany
20
5%
31
3.8%
51
4.2%
Hungary
1
0.2%
4
0.5%
5
0.4%
Israel
7
1.7%
7
0.9%
14
1.2%
Italy
12
3%
24
3%
36
3%
Japan
21
5.2%
34
4.2%
55
4.6%
Netherlands
11
2.7%
8
1%
19
1.6%
New Zealand
2
0.5%
6
0.7%
8
0.7%
Norway
3
0.7%
4
0.5%
7
0.6%
Poland
6
1.5%
28
3.5%
34
2.8%
Romania
5
1.2%
7
0.9%
12
1%
Russia
11
2.7%
24
3%
35
2.9%
Slovakia
6
1.5%
11
1.4%
17
1.4%
South Africa
17
4.2%
35
4.3%
52
4.3%
Spain
36
9%
95
11.8%
131
10.9%
Sweden
3
0.7%
10
1.2%
13
1.1%
Taiwan, Province Of China
5
1.2%
14
1.7%
19
1.6%
United Kingdom
38
9.5%
61
7.6%
99
8.2%
United States
113
28.2%
224
27.8%
337
27.9%

Outcome Measures

1. Secondary Outcome
Title Time to Metastasis (TTM)
Description Time to metastasis (TTM) was defined as the time from randomization to the time of the scan that showed first evidence of BICR-confirmed radiographically detected bone or soft tissue distant metastasis. The TTM data for participants without metastasis were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and CT or MRI of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.
Time Frame Up to approximately 43 Months

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Measure Participants 401 806
US Regulatory
16.59
40.51
EX-US Regulatory
15.70
40.51
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for TTM by BICR (US Regulatory)
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.271
Confidence Interval (2-Sided) 95%
0.219 to 0.335
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for TTM by BICR (Ex-US Regulatory)
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.279
Confidence Interval (2-Sided) 95%
0.227 to 0.342
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Progression-free Survival (PFS)
Description PFS defined as time from randomization to first documentation of BICR-confirmed radiographic progressive disease (PD) (development of distant/local/regional metastasis)/death due to any cause whichever occurred first. PFS data for participants without loco-regional disease were performed for US/ex-US regulatory purposes. Radiographic scans (bone scans and CT/MRI of chest,abdomen,pelvis) performed for detection of metastasis throughout study. PD based on RECIST v1.1; Subjects with one measurable lesion, At least 20% increase in sum of diameters of target lesions taking as reference smallest sum on study. In addition, sum must demonstrate an absolute increase of at least 5 millimeter(mm). Also, appearance of one/more new lesions was also considered PD. Subjects with non-measurable disease as per CT/MRI scans, unequivocal progression/appearance of one or more new lesions was considered PD. For new bone lesions detected on bone scans, second imaging (CT/MRI) was required to confirm PD.
Time Frame Up to approximately 43 Months

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Measure Participants 401 806
US Regulatory
14.72
40.51
EX-US Regulatory
14.65
40.51
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for PFS by BICR (US Regulatory)
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.291
Confidence Interval (2-Sided) 95%
0.238 to 0.356
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for PFS by BICR (EX-US Regulatory)
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.300
Confidence Interval (2-Sided) 95%
0.247 to 0.364
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Time to Symptomatic Progression
Description Time to symptomatic progression was defined as the time from randomization to documentation in the CRF of any of the following (whichever occurred earlier): a) development of a skeletal-related event (pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone); b) pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy; or c) development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy.
Time Frame Up to approximately 43 Months

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Measure Participants 401 806
Median (95% Confidence Interval) [Months]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for Time to Symptomatic Progression
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.447
Confidence Interval (2-Sided) 95%
0.315 to 0.634
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Overall Survival
Description Overall survival was defined as the time from randomization to the date of death due to any cause.
Time Frame Up to approximately 43 months

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Measure Participants 401 806
Median (95% Confidence Interval) [Months]
39.03
NA
5. Secondary Outcome
Title Time to Initiation of Cytotoxic Chemotherapy
Description Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
Time Frame Up to approximately 43 months

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Measure Participants 401 806
Median (95% Confidence Interval) [Months]
NA
NA
6. Primary Outcome
Title Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR)
Description MFS was defined as the time from randomization to the time of first evidence of BICR-confirmed bone or soft tissue distant metastasis or death due to any cause, whichever occurred first. The MFS data for participants without metastasis or death were performed for US or ex-US regulatory purposes. Radiographic scans (bone scans and computerized tomography [CT] or magnetic resonance imaging [MRI] of the chest, abdomen, and pelvis) were performed for detection of metastasis throughout the study.
Time Frame Up to approximately 43 Months

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
Measure Participants 401 806
US Regulatory
16.20
40.51
Ex-US Regulatory
15.70
40.51
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for MFS by BICR (US Regulatory)
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.280
Confidence Interval (2-Sided) 95%
0.227 to 0.346
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Apalutamide
Comments Statistical Analysis for MFS by BICR (Ex-US Regulatory)
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.297
Confidence Interval (2-Sided) 95%
0.244 to 0.362
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Up to approximately 43 months
Adverse Event Reporting Description Safety population included all participants who received at least one dose of study drug.
Arm/Group Title Placebo Apalutamide
Arm/Group Description Participants received apalutamide matched placebo tablets orally on a continuous once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death. Participants received apalutamide orally at a starting dose of 240 milligram (mg) (8 x 30 mg capsules then 4 x 60 mg tablets) in a continuous treatment cycles (each treatment cycle is of 28 days) once daily dosing regimen along with androgen deprivation therapy (ADT) until disease progression, withdrawal of consent or unacceptable toxicity or death.
All Cause Mortality
Placebo Apalutamide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/398 (0.3%) 10/803 (1.2%)
Serious Adverse Events
Placebo Apalutamide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 92/398 (23.1%) 199/803 (24.8%)
Blood and lymphatic system disorders
Anaemia 2/398 (0.5%) 2/803 (0.2%)
Haemolytic Uraemic Syndrome 1/398 (0.3%) 0/803 (0%)
Neutropenia 0/398 (0%) 1/803 (0.1%)
Pancytopenia 0/398 (0%) 1/803 (0.1%)
Thrombocytopenia 1/398 (0.3%) 2/803 (0.2%)
Cardiac disorders
Acute Coronary Syndrome 1/398 (0.3%) 1/803 (0.1%)
Acute Myocardial Infarction 1/398 (0.3%) 1/803 (0.1%)
Angina Pectoris 1/398 (0.3%) 1/803 (0.1%)
Angina Unstable 0/398 (0%) 1/803 (0.1%)
Aortic Valve Incompetence 0/398 (0%) 1/803 (0.1%)
Atrial Fibrillation 2/398 (0.5%) 7/803 (0.9%)
Atrial Flutter 0/398 (0%) 1/803 (0.1%)
Bradycardia 0/398 (0%) 1/803 (0.1%)
Cardiac Failure 0/398 (0%) 3/803 (0.4%)
Cardiac Failure Acute 1/398 (0.3%) 0/803 (0%)
Cardiac Failure Congestive 1/398 (0.3%) 4/803 (0.5%)
Cardiomyopathy 0/398 (0%) 2/803 (0.2%)
Coronary Artery Disease 1/398 (0.3%) 3/803 (0.4%)
Coronary Artery Occlusion 0/398 (0%) 1/803 (0.1%)
Myocardial Infarction 0/398 (0%) 3/803 (0.4%)
Myocardial Ischaemia 1/398 (0.3%) 1/803 (0.1%)
Right Ventricular Dysfunction 0/398 (0%) 1/803 (0.1%)
Sinus Node Dysfunction 0/398 (0%) 1/803 (0.1%)
Stress Cardiomyopathy 1/398 (0.3%) 0/803 (0%)
Supraventricular Tachycardia 0/398 (0%) 1/803 (0.1%)
Ventricular Tachycardia 0/398 (0%) 1/803 (0.1%)
Congenital, familial and genetic disorders
Hydrocele 1/398 (0.3%) 0/803 (0%)
Ear and labyrinth disorders
Vertigo 2/398 (0.5%) 1/803 (0.1%)
Endocrine disorders
Hypothyroidism 0/398 (0%) 1/803 (0.1%)
Eye disorders
Choroidal Haemorrhage 1/398 (0.3%) 0/803 (0%)
Open Angle Glaucoma 0/398 (0%) 1/803 (0.1%)
Retinal Detachment 0/398 (0%) 1/803 (0.1%)
Gastrointestinal disorders
Abdominal Hernia 0/398 (0%) 1/803 (0.1%)
Abdominal Pain 2/398 (0.5%) 2/803 (0.2%)
Chronic Gastritis 0/398 (0%) 1/803 (0.1%)
Colitis 1/398 (0.3%) 0/803 (0%)
Diarrhoea 1/398 (0.3%) 5/803 (0.6%)
Enteritis 0/398 (0%) 1/803 (0.1%)
Erosive Duodenitis 0/398 (0%) 1/803 (0.1%)
Gastrointestinal Haemorrhage 1/398 (0.3%) 2/803 (0.2%)
Gastrooesophageal Reflux Disease 1/398 (0.3%) 1/803 (0.1%)
Gingival Bleeding 0/398 (0%) 1/803 (0.1%)
Ileus 1/398 (0.3%) 1/803 (0.1%)
Incarcerated Umbilical Hernia 0/398 (0%) 1/803 (0.1%)
Inguinal Hernia 1/398 (0.3%) 0/803 (0%)
Inguinal Hernia Strangulated 0/398 (0%) 1/803 (0.1%)
Intestinal Haemorrhage 0/398 (0%) 1/803 (0.1%)
Intestinal Mass 1/398 (0.3%) 0/803 (0%)
Large Intestine Polyp 0/398 (0%) 1/803 (0.1%)
Lower Gastrointestinal Haemorrhage 1/398 (0.3%) 1/803 (0.1%)
Melaena 1/398 (0.3%) 1/803 (0.1%)
Mouth Ulceration 0/398 (0%) 1/803 (0.1%)
Nausea 0/398 (0%) 1/803 (0.1%)
Oesophageal Achalasia 0/398 (0%) 1/803 (0.1%)
Pancreatitis 1/398 (0.3%) 0/803 (0%)
Pancreatitis Acute 1/398 (0.3%) 0/803 (0%)
Rectal Haemorrhage 0/398 (0%) 2/803 (0.2%)
Small Intestinal Haemorrhage 1/398 (0.3%) 0/803 (0%)
Small Intestinal Obstruction 1/398 (0.3%) 2/803 (0.2%)
Umbilical Hernia 0/398 (0%) 1/803 (0.1%)
Vomiting 0/398 (0%) 2/803 (0.2%)
General disorders
Asthenia 0/398 (0%) 1/803 (0.1%)
Chest Pain 0/398 (0%) 1/803 (0.1%)
Dystrophic Calcification 0/398 (0%) 1/803 (0.1%)
Gait Disturbance 1/398 (0.3%) 1/803 (0.1%)
General Physical Health Deterioration 0/398 (0%) 2/803 (0.2%)
Hyperthermia 0/398 (0%) 1/803 (0.1%)
Multiple Organ Dysfunction Syndrome 0/398 (0%) 1/803 (0.1%)
Non-Cardiac Chest Pain 1/398 (0.3%) 3/803 (0.4%)
Oedema Peripheral 0/398 (0%) 1/803 (0.1%)
Pain 0/398 (0%) 1/803 (0.1%)
Pyrexia 0/398 (0%) 5/803 (0.6%)
Soft Tissue Inflammation 0/398 (0%) 1/803 (0.1%)
Hepatobiliary disorders
Cholangitis Acute 1/398 (0.3%) 0/803 (0%)
Cholecystitis 0/398 (0%) 3/803 (0.4%)
Cholelithiasis 1/398 (0.3%) 0/803 (0%)
Hyperbilirubinaemia 0/398 (0%) 1/803 (0.1%)
Infections and infestations
Anal Abscess 0/398 (0%) 1/803 (0.1%)
Appendiceal Abscess 1/398 (0.3%) 0/803 (0%)
Appendicitis 0/398 (0%) 2/803 (0.2%)
Bronchitis 0/398 (0%) 1/803 (0.1%)
Cellulitis 1/398 (0.3%) 3/803 (0.4%)
Cellulitis Streptococcal 0/398 (0%) 1/803 (0.1%)
Cellulitis of Male External Genital Organ 0/398 (0%) 1/803 (0.1%)
Clostridium Difficile Infection 0/398 (0%) 2/803 (0.2%)
Cystitis 1/398 (0.3%) 1/803 (0.1%)
Diverticulitis 0/398 (0%) 1/803 (0.1%)
Erysipelas 0/398 (0%) 1/803 (0.1%)
Gastroenteritis Clostridial 0/398 (0%) 1/803 (0.1%)
H1n1 Influenza 0/398 (0%) 1/803 (0.1%)
Influenza 0/398 (0%) 1/803 (0.1%)
Necrotising Fasciitis 1/398 (0.3%) 0/803 (0%)
Osteomyelitis 0/398 (0%) 2/803 (0.2%)
Pneumonia 2/398 (0.5%) 9/803 (1.1%)
Pneumonia Parainfluenzae Viral 0/398 (0%) 1/803 (0.1%)
Prostatic Abscess 0/398 (0%) 1/803 (0.1%)
Pulmonary Tuberculosis 0/398 (0%) 1/803 (0.1%)
Sepsis 0/398 (0%) 7/803 (0.9%)
Severe Fever with Thrombocytopenia Syndrome 0/398 (0%) 1/803 (0.1%)
Skin Infection 0/398 (0%) 1/803 (0.1%)
Staphylococcal Skin Infection 0/398 (0%) 1/803 (0.1%)
Urinary Tract Infection 3/398 (0.8%) 10/803 (1.2%)
Urinary Tract Infection Bacterial 0/398 (0%) 1/803 (0.1%)
Urosepsis 0/398 (0%) 5/803 (0.6%)
Injury, poisoning and procedural complications
Acetabulum Fracture 0/398 (0%) 2/803 (0.2%)
Anastomotic Complication 0/398 (0%) 1/803 (0.1%)
Ankle Fracture 0/398 (0%) 1/803 (0.1%)
Avulsion Fracture 1/398 (0.3%) 0/803 (0%)
Compression Fracture 0/398 (0%) 1/803 (0.1%)
Craniocerebral Injury 0/398 (0%) 1/803 (0.1%)
Facial Bones Fracture 0/398 (0%) 1/803 (0.1%)
Fall 1/398 (0.3%) 6/803 (0.7%)
Femoral Neck Fracture 1/398 (0.3%) 0/803 (0%)
Femur Fracture 1/398 (0.3%) 3/803 (0.4%)
Foot Fracture 0/398 (0%) 2/803 (0.2%)
Gastrointestinal Stoma Complication 1/398 (0.3%) 0/803 (0%)
Hip Fracture 0/398 (0%) 2/803 (0.2%)
Humerus Fracture 0/398 (0%) 2/803 (0.2%)
Joint Injury 0/398 (0%) 1/803 (0.1%)
Ligament Sprain 0/398 (0%) 1/803 (0.1%)
Lower Limb Fracture 0/398 (0%) 1/803 (0.1%)
Lumbar Vertebral Fracture 0/398 (0%) 3/803 (0.4%)
Perirenal Haematoma 0/398 (0%) 1/803 (0.1%)
Pneumothorax Traumatic 0/398 (0%) 1/803 (0.1%)
Procedural Pain 0/398 (0%) 1/803 (0.1%)
Pubis Fracture 0/398 (0%) 2/803 (0.2%)
Radius Fracture 0/398 (0%) 1/803 (0.1%)
Rib Fracture 0/398 (0%) 2/803 (0.2%)
Road Traffic Accident 0/398 (0%) 1/803 (0.1%)
Seroma 0/398 (0%) 1/803 (0.1%)
Spinal Fracture 0/398 (0%) 3/803 (0.4%)
Subdural Haematoma 0/398 (0%) 1/803 (0.1%)
Thoracic Vertebral Fracture 0/398 (0%) 1/803 (0.1%)
Toxicity to Various Agents 0/398 (0%) 1/803 (0.1%)
Upper Limb Fracture 0/398 (0%) 1/803 (0.1%)
Investigations
Alanine Aminotransferase Increased 0/398 (0%) 2/803 (0.2%)
Aspartate Aminotransferase Increased 0/398 (0%) 2/803 (0.2%)
Blood Bilirubin Increased 0/398 (0%) 1/803 (0.1%)
Blood Urine Present 1/398 (0.3%) 0/803 (0%)
Eastern Cooperative Oncology Group Performance Status Worsened 0/398 (0%) 1/803 (0.1%)
Weight Decreased 0/398 (0%) 2/803 (0.2%)
Metabolism and nutrition disorders
Decreased Appetite 0/398 (0%) 1/803 (0.1%)
Dehydration 0/398 (0%) 3/803 (0.4%)
Hyperglycaemia 0/398 (0%) 3/803 (0.4%)
Hyponatraemia 1/398 (0.3%) 1/803 (0.1%)
Metabolic Alkalosis 0/398 (0%) 1/803 (0.1%)
Musculoskeletal and connective tissue disorders
Arthritis 0/398 (0%) 1/803 (0.1%)
Back Pain 1/398 (0.3%) 2/803 (0.2%)
Gouty Arthritis 0/398 (0%) 1/803 (0.1%)
Joint Swelling 0/398 (0%) 1/803 (0.1%)
Lumbar Spinal Stenosis 0/398 (0%) 1/803 (0.1%)
Muscular Weakness 0/398 (0%) 1/803 (0.1%)
Musculoskeletal Chest Pain 0/398 (0%) 2/803 (0.2%)
Osteoarthritis 0/398 (0%) 5/803 (0.6%)
Osteonecrosis 0/398 (0%) 1/803 (0.1%)
Pain in Extremity 1/398 (0.3%) 0/803 (0%)
Pathological Fracture 1/398 (0.3%) 0/803 (0%)
Periarthritis 1/398 (0.3%) 0/803 (0%)
Periostitis 0/398 (0%) 1/803 (0.1%)
Polyarthritis 0/398 (0%) 1/803 (0.1%)
Polymyalgia Rheumatica 1/398 (0.3%) 0/803 (0%)
Pseudarthrosis 0/398 (0%) 1/803 (0.1%)
Spinal Flattening 0/398 (0%) 1/803 (0.1%)
Symphysiolysis 0/398 (0%) 1/803 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of Colon 0/398 (0%) 1/803 (0.1%)
Benign Neoplasm of Bladder 1/398 (0.3%) 0/803 (0%)
Bladder Cancer 1/398 (0.3%) 2/803 (0.2%)
Colon Cancer 1/398 (0.3%) 0/803 (0%)
Colon Cancer Stage Ii 0/398 (0%) 1/803 (0.1%)
Gastric Cancer 0/398 (0%) 2/803 (0.2%)
Lung Neoplasm Malignant 0/398 (0%) 2/803 (0.2%)
Malignant Melanoma 2/398 (0.5%) 0/803 (0%)
Malignant Neoplasm of Renal Pelvis 0/398 (0%) 1/803 (0.1%)
Prostate Cancer Recurrent 1/398 (0.3%) 0/803 (0%)
Rectal Cancer 1/398 (0.3%) 0/803 (0%)
Renal Cell Carcinoma 0/398 (0%) 1/803 (0.1%)
Squamous Cell Carcinoma of Lung 0/398 (0%) 1/803 (0.1%)
Transitional Cell Carcinoma 0/398 (0%) 2/803 (0.2%)
Nervous system disorders
Amnesia 1/398 (0.3%) 0/803 (0%)
Aphasia 0/398 (0%) 2/803 (0.2%)
Balance Disorder 0/398 (0%) 1/803 (0.1%)
Central Nervous System Lesion 1/398 (0.3%) 0/803 (0%)
Cerebellar Infarction 1/398 (0.3%) 0/803 (0%)
Cerebral Infarction 1/398 (0.3%) 0/803 (0%)
Cerebrovascular Accident 1/398 (0.3%) 3/803 (0.4%)
Dizziness 0/398 (0%) 1/803 (0.1%)
Haemorrhage Intracranial 1/398 (0.3%) 0/803 (0%)
Haemorrhagic Stroke 0/398 (0%) 1/803 (0.1%)
Headache 0/398 (0%) 2/803 (0.2%)
Ischaemic Stroke 0/398 (0%) 1/803 (0.1%)
Lacunar Stroke 0/398 (0%) 1/803 (0.1%)
Loss of Consciousness 0/398 (0%) 1/803 (0.1%)
Paraparesis 1/398 (0.3%) 0/803 (0%)
Polyneuropathy 0/398 (0%) 1/803 (0.1%)
Presyncope 1/398 (0.3%) 0/803 (0%)
Seizure 0/398 (0%) 2/803 (0.2%)
Spinal Cord Compression 1/398 (0.3%) 0/803 (0%)
Syncope 1/398 (0.3%) 5/803 (0.6%)
Thrombotic Cerebral Infarction 0/398 (0%) 1/803 (0.1%)
Transient Ischaemic Attack 0/398 (0%) 3/803 (0.4%)
Product Issues
Device Occlusion 0/398 (0%) 1/803 (0.1%)
Psychiatric disorders
Alcoholism 1/398 (0.3%) 0/803 (0%)
Anxiety 0/398 (0%) 1/803 (0.1%)
Confusional State 0/398 (0%) 1/803 (0.1%)
Delirium 0/398 (0%) 1/803 (0.1%)
Major Depression 0/398 (0%) 1/803 (0.1%)
Suicidal Ideation 0/398 (0%) 1/803 (0.1%)
Renal and urinary disorders
Acute Kidney Injury 4/398 (1%) 6/803 (0.7%)
Azotaemia 0/398 (0%) 1/803 (0.1%)
Bladder Mass 1/398 (0.3%) 0/803 (0%)
Bladder Neck Sclerosis 1/398 (0.3%) 0/803 (0%)
Bladder Necrosis 0/398 (0%) 1/803 (0.1%)
Calculus Urethral 0/398 (0%) 1/803 (0.1%)
Calculus Urinary 1/398 (0.3%) 0/803 (0%)
Cystitis Haemorrhagic 0/398 (0%) 1/803 (0.1%)
Dysuria 0/398 (0%) 3/803 (0.4%)
Haematuria 8/398 (2%) 13/803 (1.6%)
Hydronephrosis 8/398 (2%) 8/803 (1%)
Lower Urinary Tract Symptoms 1/398 (0.3%) 0/803 (0%)
Micturition Disorder 0/398 (0%) 1/803 (0.1%)
Pollakiuria 0/398 (0%) 1/803 (0.1%)
Renal Failure 3/398 (0.8%) 3/803 (0.4%)
Renal Impairment 0/398 (0%) 1/803 (0.1%)
Strangury 0/398 (0%) 1/803 (0.1%)
Ureteric Obstruction 0/398 (0%) 1/803 (0.1%)
Ureterolithiasis 1/398 (0.3%) 1/803 (0.1%)
Urethral Stenosis 1/398 (0.3%) 2/803 (0.2%)
Urinary Bladder Haemorrhage 1/398 (0.3%) 0/803 (0%)
Urinary Retention 15/398 (3.8%) 10/803 (1.2%)
Urinary Tract Obstruction 4/398 (1%) 2/803 (0.2%)
Reproductive system and breast disorders
Prostatic Mass 0/398 (0%) 1/803 (0.1%)
Prostatitis 0/398 (0%) 1/803 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure 0/398 (0%) 2/803 (0.2%)
Chronic Obstructive Pulmonary Disease 1/398 (0.3%) 0/803 (0%)
Chronic Respiratory Failure 0/398 (0%) 1/803 (0.1%)
Dyspnoea 1/398 (0.3%) 2/803 (0.2%)
Epistaxis 0/398 (0%) 1/803 (0.1%)
Hypoxia 1/398 (0.3%) 0/803 (0%)
Lung Disorder 0/398 (0%) 2/803 (0.2%)
Pleural Effusion 0/398 (0%) 1/803 (0.1%)
Pneumonia Aspiration 0/398 (0%) 1/803 (0.1%)
Pulmonary Embolism 1/398 (0.3%) 1/803 (0.1%)
Pulmonary Oedema 0/398 (0%) 1/803 (0.1%)
Respiratory Failure 0/398 (0%) 1/803 (0.1%)
Skin and subcutaneous tissue disorders
Eczema 0/398 (0%) 1/803 (0.1%)
Erythema Multiforme 0/398 (0%) 1/803 (0.1%)
Granuloma Annulare 0/398 (0%) 1/803 (0.1%)
Vascular disorders
Aortic Aneurysm 0/398 (0%) 2/803 (0.2%)
Arterial Occlusive Disease 1/398 (0.3%) 0/803 (0%)
Arteriosclerosis 1/398 (0.3%) 1/803 (0.1%)
Deep Vein Thrombosis 0/398 (0%) 2/803 (0.2%)
Haematoma 0/398 (0%) 1/803 (0.1%)
Hypertension 3/398 (0.8%) 1/803 (0.1%)
Hypertensive Crisis 1/398 (0.3%) 0/803 (0%)
Hypotension 0/398 (0%) 2/803 (0.2%)
Peripheral Arterial Occlusive Disease 1/398 (0.3%) 0/803 (0%)
Peripheral Ischaemia 0/398 (0%) 1/803 (0.1%)
Venous Aneurysm 0/398 (0%) 1/803 (0.1%)
Venous Thrombosis 0/398 (0%) 1/803 (0.1%)
Other (Not Including Serious) Adverse Events
Placebo Apalutamide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 329/398 (82.7%) 716/803 (89.2%)
Blood and lymphatic system disorders
Anaemia 15/398 (3.8%) 51/803 (6.4%)
Endocrine disorders
Hypothyroidism 5/398 (1.3%) 48/803 (6%)
Gastrointestinal disorders
Abdominal Discomfort 22/398 (5.5%) 37/803 (4.6%)
Abdominal Pain 33/398 (8.3%) 64/803 (8%)
Abdominal Pain Upper 32/398 (8%) 44/803 (5.5%)
Constipation 52/398 (13.1%) 87/803 (10.8%)
Diarrhoea 60/398 (15.1%) 159/803 (19.8%)
Dyspepsia 22/398 (5.5%) 58/803 (7.2%)
Nausea 63/398 (15.8%) 145/803 (18.1%)
Vomiting 24/398 (6%) 43/803 (5.4%)
General disorders
Asthenia 33/398 (8.3%) 89/803 (11.1%)
Fatigue 84/398 (21.1%) 244/803 (30.4%)
Oedema Peripheral 29/398 (7.3%) 68/803 (8.5%)
Infections and infestations
Nasopharyngitis 25/398 (6.3%) 78/803 (9.7%)
Upper Respiratory Tract Infection 21/398 (5.3%) 44/803 (5.5%)
Urinary Tract Infection 37/398 (9.3%) 57/803 (7.1%)
Injury, poisoning and procedural complications
Fall 35/398 (8.8%) 121/803 (15.1%)
Investigations
Weight Decreased 25/398 (6.3%) 128/803 (15.9%)
Metabolism and nutrition disorders
Decreased Appetite 35/398 (8.8%) 99/803 (12.3%)
Hypercholesterolaemia 6/398 (1.5%) 49/803 (6.1%)
Hyperglycaemia 15/398 (3.8%) 44/803 (5.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 30/398 (7.5%) 128/803 (15.9%)
Back Pain 59/398 (14.8%) 100/803 (12.5%)
Pain in Extremity 20/398 (5%) 73/803 (9.1%)
Nervous system disorders
Dizziness 25/398 (6.3%) 74/803 (9.2%)
Dysgeusia 6/398 (1.5%) 57/803 (7.1%)
Headache 25/398 (6.3%) 75/803 (9.3%)
Psychiatric disorders
Insomnia 21/398 (5.3%) 55/803 (6.8%)
Renal and urinary disorders
Dysuria 22/398 (5.5%) 41/803 (5.1%)
Haematuria 34/398 (8.5%) 60/803 (7.5%)
Nocturia 29/398 (7.3%) 39/803 (4.9%)
Pollakiuria 34/398 (8.5%) 45/803 (5.6%)
Urinary Incontinence 15/398 (3.8%) 42/803 (5.2%)
Urinary Retention 24/398 (6%) 28/803 (3.5%)
Respiratory, thoracic and mediastinal disorders
Cough 28/398 (7%) 58/803 (7.2%)
Dyspnoea 15/398 (3.8%) 63/803 (7.8%)
Skin and subcutaneous tissue disorders
Pruritus 6/398 (1.5%) 50/803 (6.2%)
Rash 13/398 (3.3%) 87/803 (10.8%)
Rash Maculo-Papular 2/398 (0.5%) 43/803 (5.4%)
Vascular disorders
Hot Flush 34/398 (8.5%) 113/803 (14.1%)
Hypertension 77/398 (19.3%) 198/803 (24.7%)

Limitations/Caveats

These results are up to clinical cutoff (CCO) date (that is, 19 May 2017).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.

Results Point of Contact

Name/Title Senior Medical Director, WC Clinical Oncology Department
Organization Janssen Research & Development, LLC
Phone 844-434-4210
Email ClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01946204
Other Study ID Numbers:
  • CR102931
  • ARN-509-003
  • 2012-004322-24
First Posted:
Sep 19, 2013
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022