SPARTAN: A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer
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
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
- 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
- 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.
- 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.
- 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.
- 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.
- 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
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.- CR102931
- ARN-509-003
- 2012-004322-24
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
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 |
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 |
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 |
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
|
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
|
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
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 |
ClinicalTrialDisclosure@its.jnj.com |
- CR102931
- ARN-509-003
- 2012-004322-24