Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer (IPATential150)

• ClinicalTrials.gov Identifier: NCT03072238
• Recruitment Status: Active, not recruiting
• First Posted: March 7, 2017
• Results First Posted: April 10, 2023
• Last Update Posted: April 16, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Metastatic Prostate Cancer
• Interventions: Drug: Ipatasertib; Drug: Abiraterone; Drug: Placebo; Drug: Prednisone/Prednisolone
• Enrollment: 1101

Participant Flow

Recruitment Details	The study was conducted at 181 centers in 26 countries.
Pre-assignment Details	A total of 1611 participants were screened, out of which 510 participants failed screening. A total of 1101 participants were enrolled at 181 sites.

Arm/Group Title	Placebo + Abiraterone	Ipatasertib + Abiraterone
Arm/Group Description	Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
Period Title: Overall Study
Started	554	547
Completed	0	0
Not Completed	554	547
Reason Not Completed
Withdrawal by Subject	30	51
Lost to Follow-up	7	4
Physician Decision	1	3
Death	139	121
Other	0	1
Ongoing on study	377	367

Baseline Characteristics

Arm/Group Title		Placebo + Abiraterone	Ipatasertib + Abiraterone	Total
Arm/Group Description		Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Total of all reporting groups
Overall Number of Baseline Participants		554	547	1101
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	554 participants	547 participants	1101 participants
		69.7 (8.2)	69.4 (8.0)	69.5 (8.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	554 participants	547 participants	1101 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	554 100.0%	547 100.0%	1101 100.0%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	554 participants	547 participants	1101 participants
Hispanic or Latino		65	66	131
Not Hispanic or Latino		469	452	921
Not Stated		13	14	27
Unknown		7	15	22
		[1] Measure Description: Ethnicity
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	554 participants	547 participants	1101 participants
American Indian or Alaska Native		16	15	31
Asian		109	110	219
Black or African American		9	10	19
Native Hawaiian or other Pacific Islander		1	1	2
White		386	376	762
Unknown		33	35	68
		[1] Measure Description: Race

Outcome Measures

1. Primary Outcome

Title	Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (PTEN Loss Population)
Description	Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in participants with phosphatase and tensin homolog (PTEN) - loss tumors (using the Ventana PTEN immunohistochemistry (IHC) assay).
Time Frame	Up to approximately 31 months

Outcome Measure Data

Analysis Population Description

The PTEN Loss Population was defined as all randomized participants with PTEN Loss tumours by IHC, regardless of whether or not the participant received the assigned treatment.

Arm/Group Title	Placebo + Abiraterone	Ipatasertib + Abiraterone
Arm/Group Description:	Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
Overall Number of Participants Analyzed	261	260
Median (95% Confidence Interval); Unit of Measure: Months
	16.5; (13.9 to 17.0)	18.5; (16.3 to 22.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Abiraterone, Ipatasertib + Abiraterone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0335
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.61 to 0.98
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (Intent-To-Treat (ITT) Population)
Description	Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in the Intent-to-Treat (ITT) population.
Time Frame	Up to approximately 31 months

Outcome Measure Data

Analysis Population Description

The ITT Population was defined as all randomized participants, whether or not the participant received the assigned treatment. The ITT participants were analyzed according to the treatment assigned at randomization by the IxRS.

Arm/Group Title	Placebo + Abiraterone	Ipatasertib + Abiraterone
Arm/Group Description:	Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
Overall Number of Participants Analyzed	554	547
Median (95% Confidence Interval); Unit of Measure: Months
	16.6; (15.6 to 19.1)	19.2; (16.5 to 22.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Abiraterone, Ipatasertib + Abiraterone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0431
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.71 to 0.99
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) is defined as the time from randomization to death due to any cause. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Time to Pain Progression
Description	Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who are asymptomatic at baseline or pain worsening for those who are mildly symptomatic at baseline. Pain severity will be graded on a 10-point scale, with 0=no pain and 10=severe pain. Pain severity progression is defined as a ≥ 2-point absolute increase from baseline. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Time to Initiation of Cytotoxic Chemotherapy
Description	Time to initiation of cytotoxic chemotherapy is defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for prostate cancer. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Time to Function Deterioration
Description	Time to function deterioration was defined as the time from the date of randomisation to the date of 10-point or more decrease on either the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) PF (Physical Functioning) or RF (Role Functioning) scale scores (range, 0-100) held for two consecutive assessments, or a 10 point or more score decrease followed by death (any cause) within 28 days, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA) Progression
Description	Time to PSA progression is defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression is defined as a PSA increase that is ≥ 25% and ≥ 2 ng/mL above the baseline or the nadir, which is confirmed by a second value ≥ 3 weeks later. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Time to First Opioid Use
Description	Time to first opioid use is defined as the documentation of the first opioid prescription for cancer-related pain followed by the participant's record of opioid intake or availability of an Analgesic Quantification Algorithm (AQA) daily score. Participants reporting use of opioid for cancer-related pain at baseline will be excluded from the analysis. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

9. Secondary Outcome

Title	Time to Symptomatic Skeletal Event (SSE)
Description	Time to SSE is defined as the time interval from the date of randomization to the date of an SSE. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

10. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	An objective response is defined as a complete response (CR) or partial response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria, in participants with measurable disease at baseline. Participants without a post-baseline tumor assessment will be considered non-responders. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

11. Secondary Outcome

Title	PSA Response Rate
Description	PSA response rate is defined as the percentage of participants achieving a PSA decline ≥50% from baseline. Participants without a post-baseline PSA assessment will be considered non-responders. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

12. Secondary Outcome

Title	Investigator-Assessed rPFS Per PCWG3 Criteria in Participants With PTEN-Loss Tumors by Next-Generation Sequencing (NGS)
Description	Investigator-assessed rPFS is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first and will be analyzed in participants with PTEN-loss tumors by NGS. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

13. Secondary Outcome

Title	Duration of Response (DOR)
Description	Duration of Response (DOR) is defined as the time from first occurrence of a documented confirmed objective response until the time of documented disease progression as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Up to approximately 7 years

Outcome Measure Data Not Reported

14. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time Frame	Baseline up until 28 days after the last dose of study drug or initiation of subsequent lines of anti-cancer therapy, whichever occurs first (up to a maximum of 7 years).

Outcome Measure Data Not Reported

15. Secondary Outcome

Title	Plasma Concentrations of Ipatasertib at Specified Timepoints
Description	Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time Frame	1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days)

Outcome Measure Data

Analysis Population Description

The PK Evaluable population was defined as all participants who received Ipatasertib treatment with evaluable PK samples. Number Analyzed was the number of participants with data available for analyses at the specified timepoint.

Arm/Group Title		Ipatasertib + Abiraterone
Arm/Group Description:		Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
Overall Number of Participants Analyzed		544
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Cycle 1 Day 1 Post-dose	Number Analyzed	499 participants
		212; (158%)
Cycle 1 Day 15 Pre-dose	Number Analyzed	467 participants
		46.8; (160%)
Cycle 1 Day 15 Post-dose	Number Analyzed	413 participants
		247; (138%)
Cycle 3 Day 1 Pre-dose	Number Analyzed	407 participants
		35.4; (256%)
Cycle 3 Day 1 Post-dose	Number Analyzed	403 participants
		207; (156%)
Cycle 6 Day 1 Pre-dose	Number Analyzed	372 participants
		46.1; (134%)

16. Secondary Outcome

Title	Plasma Concentrations of Abiraterone at Specified Timepoints
Description	Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time Frame	Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days)

Outcome Measure Data

Analysis Population Description

The PK Evaluable population was defined as all participants who received Abiraterone treatment with evaluable PK samples. Number Analyzed is the number of participants with data available for analyses at the specified timepoint.

Arm/Group Title		Placebo + Abiraterone	Ipatasertib + Abiraterone
Arm/Group Description:		Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
Overall Number of Participants Analyzed		537	520
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Cycle 1 Day 15	Number Analyzed	508 participants	470 participants
		11.2; (124%)	9.40; (159%)
Cycle 3 Day 1	Number Analyzed	492 participants	415 participants
		10.4; (120%)	9.55; (159%)

Adverse Events

Time Frame	Baseline up until 28 days after the last dose of study drug or initiation of subsequent lines of anti-cancer therapy, whichever occurs first (up to a maximum of 7 years).
Adverse Event Reporting Description	In total, 4 participants from both treatment arms did not receive any study treatment. Additionally, 5 participants randomized to the placebo arm took at least one dose of ipatasertib prior to the Clinical Cut-off Date (CCOD) of 16th March 2020 and so as a result, the safety-evaluable population comprised 1097 participants (551 in the Ipat + Abi arm and 546 in the Pbo + Abi arm).
Arm/Group Title	Placebo + Abiraterone		Ipatasertib + Abiraterone
Arm/Group Description	Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.		Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
All-Cause Mortality
	Placebo + Abiraterone		Ipatasertib + Abiraterone
	Affected / at Risk (%)		Affected / at Risk (%)
Total	143/546 (26.19%)		126/551 (22.87%)
Serious Adverse Events
	Placebo + Abiraterone		Ipatasertib + Abiraterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/546 (22.71%)		218/551 (39.56%)
Blood and lymphatic system disorders
Anaemia † 1	2/546 (0.37%)	2	4/551 (0.73%)	4
Bicytopenia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Febrile neutropenia † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Haemolysis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Immune thrombocytopenia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Thrombocytopenia † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Cardiac disorders
Acute coronary syndrome † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Acute left ventricular failure † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Acute myocardial infarction † 1	6/546 (1.10%)	6	3/551 (0.54%)	3
Angina pectoris † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Angina unstable † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Atrial fibrillation † 1	2/546 (0.37%)	2	1/551 (0.18%)	1
Atrial flutter † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Bradycardia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Cardiac arrest † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Cardiac failure † 1	0/546 (0.00%)	0	3/551 (0.54%)	3
Cardiac failure congestive † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Cardiomyopathy † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Cor pulmonale † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Coronary artery stenosis † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Myocardial infarction † 1	1/546 (0.18%)	1	5/551 (0.91%)	5
Myocardial ischaemia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Sinus tachycardia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Eye disorders
Cataract † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Retinal detachment † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Gastrointestinal disorders
Abdominal distension † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Abdominal pain † 1	2/546 (0.37%)	2	0/551 (0.00%)	0
Anal haemorrhage † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Chronic gastritis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Colonic fistula † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Diarrhoea † 1	0/546 (0.00%)	0	12/551 (2.18%)	12
Duodenal ulcer † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Duodenal ulcer haemorrhage † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Dysphagia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Enterocolitis † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Gastritis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Gastritis haemorrhagic † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Gastrointestinal haemorrhage † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Gastrooesophageal reflux disease † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Haematemesis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Ileus † 1	2/546 (0.37%)	2	2/551 (0.36%)	2
Ileus paralytic † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Incarcerated inguinal hernia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Intestinal obstruction † 1	2/546 (0.37%)	2	2/551 (0.36%)	2
Intra-abdominal haematoma † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Ischaemic enteritis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Large intestine polyp † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Nausea † 1	1/546 (0.18%)	1	1/551 (0.18%)	2
Oesophagitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pancreatitis † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Pancreatitis acute † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Rectal haemorrhage † 1	2/546 (0.37%)	2	0/551 (0.00%)	0
Small intestinal obstruction † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Small intestinal perforation † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Volvulus † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Vomiting † 1	1/546 (0.18%)	1	4/551 (0.73%)	4
General disorders
Adverse drug reaction † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Asthenia † 1	1/546 (0.18%)	1	2/551 (0.36%)	2
Chest pain † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Death † 1	2/546 (0.37%)	2	3/551 (0.54%)	3
Fatigue † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
General physical health deterioration † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Hernia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Impaired healing † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Non-cardiac chest pain † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Oedema peripheral † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pain † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Pyrexia † 1	3/546 (0.55%)	4	3/551 (0.54%)	3
Sudden cardiac death † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Hepatobiliary disorders
Bile duct obstruction † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Cholangitis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Cholecystitis † 1	2/546 (0.37%)	2	1/551 (0.18%)	1
Drug-induced liver injury † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Haemobilia † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Hepatic function abnormal † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Hepatitis acute † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Hepatotoxicity † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Hypertransaminasaemia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Infections and infestations
Acute sinusitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Anal abscess † 1	2/546 (0.37%)	2	2/551 (0.36%)	2
Bronchiolitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Bronchitis † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Bullous erysipelas † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
COVID-19 † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Cellulitis † 1	1/546 (0.18%)	1	3/551 (0.54%)	3
Cystitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Diverticulitis † 1	2/546 (0.37%)	2	2/551 (0.36%)	2
Enterocolitis infectious † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Febrile infection † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Gastroenteritis † 1	3/546 (0.55%)	3	1/551 (0.18%)	1
Gastroenteritis bacterial † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Gastroenteritis salmonella † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Gingivitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Infection † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Infectious pleural effusion † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Influenza † 1	3/546 (0.55%)	3	0/551 (0.00%)	0
Localised infection † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Lower respiratory tract infection † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Opportunistic infection † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Osteomyelitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pneumonia † 1	7/546 (1.28%)	7	13/551 (2.36%)	14
Pneumonia bacterial † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Pneumonia influenzal † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pneumonia legionella † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pneumonia pneumococcal † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Pulpitis dental † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pyelonephritis † 1	1/546 (0.18%)	2	2/551 (0.36%)	2
Pyelonephritis acute † 1	1/546 (0.18%)	1	2/551 (0.36%)	2
Rash pustular † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Renal abscess † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Respiratory tract infection † 1	1/546 (0.18%)	1	2/551 (0.36%)	2
Sepsis † 1	3/546 (0.55%)	3	3/551 (0.54%)	3
Septic shock † 1	0/546 (0.00%)	0	4/551 (0.73%)	4
Skin infection † 1	0/546 (0.00%)	0	2/551 (0.36%)	3
Tooth infection † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Tracheobronchitis † 1	2/546 (0.37%)	2	0/551 (0.00%)	0
Upper respiratory tract infection † 1	1/546 (0.18%)	1	2/551 (0.36%)	2
Urinary tract infection † 1	4/546 (0.73%)	4	8/551 (1.45%)	10
Injury, poisoning and procedural complications
Cystitis radiation † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Fall † 1	3/546 (0.55%)	3	2/551 (0.36%)	2
Forearm fracture † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Fracture displacement † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Head injury † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Hip fracture † 1	1/546 (0.18%)	1	2/551 (0.36%)	2
Humerus fracture † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Hypobarism † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Lumbar vertebral fracture † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Patella fracture † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pneumonitis chemical † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Radiation proctitis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Skull fracture † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Spinal compression fracture † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Spinal fracture † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Subdural haematoma † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Subdural haemorrhage † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Tendon rupture † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Traumatic intracranial haemorrhage † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Upper limb fracture † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Investigations
Alanine aminotransferase increased † 1	1/546 (0.18%)	1	7/551 (1.27%)	7
Aspartate aminotransferase increased † 1	1/546 (0.18%)	1	5/551 (0.91%)	5
Blood bilirubin increased † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Glycosylated haemoglobin increased † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Transaminases increased † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Dehydration † 1	0/546 (0.00%)	0	11/551 (2.00%)	12
Diabetes mellitus † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Electrolyte imbalance † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Hyperglycaemia † 1	1/546 (0.18%)	1	23/551 (4.17%)	24
Hypokalaemia † 1	1/546 (0.18%)	1	3/551 (0.54%)	3
Hyponatraemia † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Hypophosphataemia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Metabolic acidosis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Type 2 diabetes mellitus † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Arthritis reactive † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Back pain † 1	6/546 (1.10%)	8	5/551 (0.91%)	5
Bone pain † 1	0/546 (0.00%)	0	2/551 (0.36%)	3
Fasciitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Intervertebral disc protrusion † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Muscular weakness † 1	3/546 (0.55%)	3	2/551 (0.36%)	2
Musculoskeletal pain † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Osteoarthritis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Osteonecrosis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Rhabdomyolysis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Bladder transitional cell carcinoma † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Gastric cancer † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Gastrointestinal stromal tumour † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Lung neoplasm malignant † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Malignant melanoma † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Metastases to meninges † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Pancreatic carcinoma † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Schwannoma † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Tonsil cancer † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Nervous system disorders
Cerebral haemorrhage † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Cerebral ischaemia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Cerebrospinal fluid leakage † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Cerebrovascular accident † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Dysarthria † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Headache † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Paraplegia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Sciatica † 1	2/546 (0.37%)	2	1/551 (0.18%)	1
Seizure † 1	2/546 (0.37%)	2	2/551 (0.36%)	2
Spinal cord compression † 1	2/546 (0.37%)	2	1/551 (0.18%)	1
Syncope † 1	1/546 (0.18%)	1	1/551 (0.18%)	1
Product Issues
Device dislocation † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Psychiatric disorders
Confusional state † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Disorientation † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Psychotic disorder † 1	2/546 (0.37%)	2	0/551 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	3/546 (0.55%)	3	3/551 (0.54%)	3
Dysuria † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Haematuria † 1	4/546 (0.73%)	5	10/551 (1.81%)	10
Hydronephrosis † 1	0/546 (0.00%)	0	2/551 (0.36%)	2
Nephrolithiasis † 1	1/546 (0.18%)	1	3/551 (0.54%)	3
Renal failure † 1	0/546 (0.00%)	0	2/551 (0.36%)	3
Renal tubular necrosis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Ureterolithiasis † 1	2/546 (0.37%)	2	1/551 (0.18%)	1
Urethral stenosis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Urinary retention † 1	2/546 (0.37%)	2	1/551 (0.18%)	1
Urinary tract obstruction † 1	4/546 (0.73%)	4	0/551 (0.00%)	0
Reproductive system and breast disorders
Prostatitis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	2/546 (0.37%)	2	0/551 (0.00%)	0
Epistaxis † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Hypoxia † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Pneumonia aspiration † 1	1/546 (0.18%)	1	0/551 (0.00%)	0
Pneumonitis † 1	2/546 (0.37%)	2	0/551 (0.00%)	0
Pulmonary embolism † 1	1/546 (0.18%)	1	4/551 (0.73%)	4
Skin and subcutaneous tissue disorders
Dermatitis allergic † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Dermatitis exfoliative † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Drug reaction with eosinophilia and systemic symptoms † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Erythema † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Erythema multiforme † 1	0/546 (0.00%)	0	3/551 (0.54%)	3
Rash † 1	0/546 (0.00%)	0	15/551 (2.72%)	17
Rash maculo-papular † 1	0/546 (0.00%)	0	5/551 (0.91%)	5
Stevens-Johnson syndrome † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Toxic skin eruption † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Vascular disorders
Artery dissection † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Deep vein thrombosis † 1	0/546 (0.00%)	0	3/551 (0.54%)	3
Hypertension † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Hypotension † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
Venous thrombosis † 1	0/546 (0.00%)	0	1/551 (0.18%)	1
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo + Abiraterone		Ipatasertib + Abiraterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	486/546 (89.01%)		541/551 (98.19%)
Blood and lymphatic system disorders
Anaemia † 1	65/546 (11.90%)	85	107/551 (19.42%)	147
Gastrointestinal disorders
Abdominal pain † 1	18/546 (3.30%)	20	31/551 (5.63%)	37
Constipation † 1	78/546 (14.29%)	90	44/551 (7.99%)	47
Diarrhoea † 1	123/546 (22.53%)	164	437/551 (79.31%)	914
Dyspepsia † 1	23/546 (4.21%)	28	35/551 (6.35%)	37
Nausea † 1	54/546 (9.89%)	62	154/551 (27.95%)	193
Vomiting † 1	47/546 (8.61%)	57	92/551 (16.70%)	139
General disorders
Asthenia † 1	68/546 (12.45%)	82	99/551 (17.97%)	135
Fatigue † 1	94/546 (17.22%)	114	120/551 (21.78%)	137
Oedema peripheral † 1	48/546 (8.79%)	56	71/551 (12.89%)	80
Pyrexia † 1	20/546 (3.66%)	22	31/551 (5.63%)	37
Infections and infestations
Nasopharyngitis † 1	45/546 (8.24%)	62	44/551 (7.99%)	58
Upper respiratory tract infection † 1	49/546 (8.97%)	58	36/551 (6.53%)	46
Urinary tract infection † 1	39/546 (7.14%)	48	41/551 (7.44%)	58
Injury, poisoning and procedural complications
Fall † 1	45/546 (8.24%)	59	34/551 (6.17%)	45
Investigations
Alanine aminotransferase increased † 1	56/546 (10.26%)	65	110/551 (19.96%)	127
Aspartate aminotransferase increased † 1	59/546 (10.81%)	72	94/551 (17.06%)	101
Blood creatinine increased † 1	18/546 (3.30%)	21	34/551 (6.17%)	39
Weight decreased † 1	16/546 (2.93%)	18	67/551 (12.16%)	81
Metabolism and nutrition disorders
Decreased appetite † 1	51/546 (9.34%)	64	98/551 (17.79%)	113
Hyperglycaemia † 1	85/546 (15.57%)	125	211/551 (38.29%)	330
Hypertriglyceridaemia † 1	22/546 (4.03%)	28	31/551 (5.63%)	35
Hypokalaemia † 1	35/546 (6.41%)	55	43/551 (7.80%)	62
Musculoskeletal and connective tissue disorders
Arthralgia † 1	75/546 (13.74%)	80	65/551 (11.80%)	84
Back pain † 1	107/546 (19.60%)	128	81/551 (14.70%)	94
Bone pain † 1	30/546 (5.49%)	42	39/551 (7.08%)	42
Musculoskeletal pain † 1	34/546 (6.23%)	38	30/551 (5.44%)	36
Pain in extremity † 1	41/546 (7.51%)	50	38/551 (6.90%)	44
Nervous system disorders
Dizziness † 1	34/546 (6.23%)	42	36/551 (6.53%)	41
Headache † 1	42/546 (7.69%)	50	53/551 (9.62%)	60
Psychiatric disorders
Insomnia † 1	41/546 (7.51%)	44	24/551 (4.36%)	25
Renal and urinary disorders
Haematuria † 1	27/546 (4.95%)	32	31/551 (5.63%)	39
Respiratory, thoracic and mediastinal disorders
Cough † 1	45/546 (8.24%)	48	45/551 (8.17%)	49
Dyspnoea † 1	27/546 (4.95%)	28	32/551 (5.81%)	33
Skin and subcutaneous tissue disorders
Pruritus † 1	15/546 (2.75%)	17	45/551 (8.17%)	60
Rash † 1	42/546 (7.69%)	46	141/551 (25.59%)	178
Rash maculo-papular † 1	6/546 (1.10%)	7	47/551 (8.53%)	65
Vascular disorders
Hot flush † 1	36/546 (6.59%)	39	27/551 (4.90%)	29
Hypertension † 1	82/546 (15.02%)	113	76/551 (13.79%)	91
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kotani N, Wilkins JJ, Wade JR, Dang S, Sutaria DS, Yoshida K, Sundrani S, Ding H, Garcia J, Hinton H, Sane R, Chanu P. Characterization of exposure-response relationships of ipatasertib in patients with metastatic castration-resistant prostate cancer in the IPATential150 study. Cancer Chemother Pharmacol. 2022 Dec;90(6):511-521. doi: 10.1007/s00280-022-04488-2. Epub 2022 Oct 28.

Sweeney C, Bracarda S, Sternberg CN, Chi KN, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Parnis F, Atduev V, Buchschacher GL Jr, Gafanov R, Corrales L, Borre M, Stroyakovskiy D, Alves GV, Bournakis E, Puente J, Harle-Yge ML, Gallo J, Chen G, Hanover J, Wongchenko MJ, Garcia J, de Bono JS. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2021 Jul 10;398(10295):131-142. doi: 10.1016/S0140-6736(21)00580-8.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03072238
• Other Study ID Numbers: CO39303; 2016-004429-17 ( EudraCT Number )
• First Submitted: March 2, 2017
• First Posted: March 7, 2017
• Results First Submitted: March 15, 2023
• Results First Posted: April 10, 2023
• Last Update Posted: April 16, 2024