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Clinical Trial Results:
Phase 1/2a dose-escalation and expansion study to evaluate the safety, tolerability, and pharmacokinetics of CORT125281 with enzalutamide in patients with metastatic castration-resistant prostate cancer.

Summary
EudraCT number	2017-003287-12
Trial protocol	GB
Global end of trial date	12 Jan 2023

Results information
Results version number	v1(current)
This version publication date	17 Oct 2026
First version publication date	17 Oct 2026
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CORT125281-601

ISRCTN number

US NCT number

NCT03437941

WHO universal trial number (UTN)

Sponsor organisation name

Corcept Therapeutics

Sponsor organisation address

149 Commonwealth Drive, Menlo Park, United States,

Public contact

Clinical Operations, Corcept Therapeutics, +1 650 3273270, clinicalstudies@corcept.com

Scientific contact

Clinical Operations, Corcept Therapeutics, +1 650 3273270, clinicalstudies@corcept.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Jan 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Jan 2023

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective was to determine the maximum tolerated dose (MTD) and/or biologically active doses of exicorilant in combination with enzalutamide to identify the recommended dose (RD) for Phase 2 studies.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Feb 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

United States: 27

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

By Sponsor decision, no patients were enrolled in the study after the Dose Determination Segment 2; thus, no patients were enrolled in the Dose Expansion arms.

Screening details

Patients were screened 28 days before the first dose of study treatment. A total of 58 patients were screened and 39 were enrolled.

Number of subjects started

Number of subjects completed

Reason: Number of subjects

Death: 1

Reason: Number of subjects

Consent withdrawn by subject: 1

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant

Arm description

Patients in this dose determination cohort received lead-in enzalutamide monotherapy once daily for 28 days. Patients then received combination treatment with twice-daily exicorilant 180 mg (total daily dose 360 mg) and enzalutamide once daily in 28-day dosing cycles.

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant

Arm description

Patients in this dose determination cohort received lead-in enzalutamide monotherapy once daily for 28 days. Patients then received combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant

Arm description

Patients in this dose determination cohort did not receive lead-in enzalutamide monotherapy. Patients received combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Segment 2: Arm A - Maximum Dose 240 mg Exicorilant

Arm description

Patients in this dose determination arm received treatment with once-daily exicorilant starting at 240 mg and titrating to 280 mg and then to 320 mg at 2-week intervals, as tolerated, in combination with enzalutamide once daily in 28-day dosing cycles. Patients in this arm are reported at the highest titrated dose of exicorilant achieved: 240 mg exicorilant.

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Segment 2: Arm A - Maximum Dose 280 mg Exicorilant

Arm description

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Segment 2: Arm A - Maximum Dose 320 mg Exicorilant

Arm description

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Segment 2: Arm B - 240 mg Exicorilant

Arm description

Patients in this dose determination arm received combination treatment with once-daily exicorilant 240 mg, enzalutamide once daily, and placebo in 28-day dosing cycles.

Arm type

Experimental

Investigational medicinal product name

Exicorilant

Investigational medicinal product code

Other name

CORT125281

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Exicorilant was supplied as capsules for oral dosing.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was taken orally.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo capsules matched the appearance of the exicorilant capsules.

Number of subjects in period 1 ^[1]	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Started	2	3	7	8	1	10	6
Completed	0	0	0	0	0	0	0
Not completed	2	3	7	8	1	10	6
Physician decision	1	-	-	-	-	-	-
Consent withdrawn by subject	-	-	-	-	-	2	-
Study terminated by Sponsor	-	2	2	7	1	3	2
Death	1	1	5	1	-	5	4

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Two patients were enrolled in the study but discontinued before being allocated into a treatment group.

Baseline characteristics

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Reporting group title

Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant

Reporting group description

Reporting group title

Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant

Reporting group description

Patients in this dose determination cohort received lead-in enzalutamide monotherapy once daily for 28 days. Patients then received combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.

Reporting group title

Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 240 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 280 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 320 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm B - 240 mg Exicorilant

Reporting group description

Patients in this dose determination arm received combination treatment with once-daily exicorilant 240 mg, enzalutamide once daily, and placebo in 28-day dosing cycles.

Reporting group values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant	Total
Number of subjects	2	3	7	8	1	10	6	37
Age categorical
Units: Subjects
Age continuous
Units: years
median (full range (min-max))	67.5 (59 to 76)	60.0 (53 to 71)	70.0 (58 to 80)	72.0 (60 to 82)	75.0 (75 to 75)	64.0 (53 to 76)	66.0 (55 to 74)	-
Gender categorical
Units: Subjects
Female	0	0	0	0	0	0	0	0
Male	2	3	7	8	1	10	6	37
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	0	0
Not Hispanic or Latino	1	3	7	7	1	8	5	32
Unknown or Not Reported	1	0	0	1	0	2	1	5
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	1	1	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	0	1	0	1	0	2	0	4
White	2	2	7	4	1	5	5	26
More than one race	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	3	0	2	0	5

End points

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Reporting group title

Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant

Reporting group description

Reporting group title

Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant

Reporting group description

Patients in this dose determination cohort received lead-in enzalutamide monotherapy once daily for 28 days. Patients then received combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.

Reporting group title

Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 240 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 280 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 320 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm B - 240 mg Exicorilant

Reporting group description

Patients in this dose determination arm received combination treatment with once-daily exicorilant 240 mg, enzalutamide once daily, and placebo in 28-day dosing cycles.

Primary: Number of Patients With One or More Dose-Limiting Toxicity (DLT)

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End point title

Number of Patients With One or More Dose-Limiting Toxicity (DLT) ^[1]

End point description

Assess the maximum tolerated dose (MTD) and/or biologically active doses of exicorilant in combination with enzalutamide to identify the recommended dose (RD) for Phase 2 studies based on the number of patients who experienced a DLT while receiving exicorilant in combination with enzalutamide. DLTs were defined as any of the protocol-specified toxicities that the Investigator considered possibly or probably related to study drug that occurred during the DLT-evaluation period. The MTD was defined as the highest dose at which the DLT rate was <33%. The DLT-Evaluable Population included all patients in the Dose-Determination cohorts who received at least 1 dose of exicorilant and fulfilled at least 1 of the following: 1) received at least 75% of the study regimen; 2) experienced a DLT within the DLT-evaluation period.

End point type

Primary

End point timeframe

From first dose of exicorilant through completion of Cycle 1 (up to 28 days) for Segment 1 and from first dose of exicorilant through completion of Cycle 3 (up to 84 days) for Segment 2.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were planned for this endpoint.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2	3	6	4	1	5	6
Units: Patients	2	1	0	4	1	0	1

No statistical analyses for this end point

Secondary: Number of Patients With 1 or More Treatment-Emergent Adverse Events

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End point title

Number of Patients With 1 or More Treatment-Emergent Adverse Events

End point description

The safety of each treatment group was assessed by evaluating the incidence of treatment-emergent adverse events. The Safety Population included all patients who received ≥1 dose of exicorilant.

End point type

Secondary

End point timeframe

Up to 27 months for Segment 1 and up to 19 months for Segment 2

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2	3	7	8	1	10	6
Units: Patients	2	3	7	8	1	10	6

No statistical analyses for this end point

Secondary: Area Under the Concentration Versus Time Curve (AUC) of Plasma Exicorilant: Segment 1

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End point title

Area Under the Concentration Versus Time Curve (AUC) of Plasma Exicorilant: Segment 1 ^[2]

End point description

AUC from time zero to 12 hours postdose (AUC0-12) calculated using linear up and log down method. The PK-Evaluable Population included all patients who received active study treatment and had measurable plasma concentration of study treatment at any time point.

End point type

Secondary

End point timeframe

Predose and at time intervals up to 12 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2	3 ^[3]	7 ^[4]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1	387 ( 11.3 )	275 ( 64.2 )	477 ( 82.4 )
Cycle 2 Day 1	433 ( 14.8 )	431 ( 29.0 )	747 ( 82.2 )

Notes
[3] - Patients analyzed in each category: N=3, N=2
[4] - Patients analyzed in each category: N=5, N=5

No statistical analyses for this end point

Secondary: Maximum Observed Concentration (Cmax) of Plasma Exicorilant: Segment 1

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End point title

Maximum Observed Concentration (Cmax) of Plasma Exicorilant: Segment 1 ^[5]

End point description

Maximum observed concentration over the dosing interval. The PK-Evaluable Population included all patients who received active study treatment and had measurable plasma concentration of study treatment at any time point.

End point type

Secondary

End point timeframe

Predose and at time intervals up to 12 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2	3 ^[6]	7 ^[7]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1	84.2 ( 24.5 )	91.6 ( 34.5 )	186.1 ( 70.5 )
Cycle 2 Day 1	108 ( 59.2 )	125 ( 15.4 )	174 ( 68.7 )

Notes
[6] - Patients analyzed in each category: N=3, N=2
[7] - Patients analyzed in each category: N=5, N=5

No statistical analyses for this end point

Secondary: AUC of Plasma Enzalutamide: Segment 1

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End point title

AUC of Plasma Enzalutamide: Segment 1 ^[8]

End point description

AUC from time zero to 24 hours postdose (AUC0-24) calculated using linear up and log down method. The PK-Evaluable Population included all patients who received active study treatment and had measurable plasma concentration of study treatment at any time point.

End point type

Secondary

End point timeframe

Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2 ^[9]	3 ^[10]	7 ^[11]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day -1 lead-in	281499 ( 2.7 )	255623 ( 20.0 )	9999 ( 9999 )
Cycle 1 Day 1	307849 ( 9999 )	278573 ( 25.6 )	36979 ( 21.4 )
Cycle 2 Day 1	334761 ( 3.8 )	410557 ( 16.3 )	386651 ( 15.3 )

Notes
[9] - Patients analyzed in each category: N=2, N=1, N=1. Missing values are indicated by "9999".
[10] - Patients analyzed in each category: N=3, N=2, N=2
[11] - Patients analyzed in each category: N=0, N=6, N=5. Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Cmax of Plasma Enzalutamide: Segment 1

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End point title

Cmax of Plasma Enzalutamide: Segment 1 ^[12]

End point description

End point type

Secondary

End point timeframe

Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2	3 ^[13]	7 ^[14]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 Lead-in	15112 ( 15.5 )	12759 ( 27.5 )	9999 ( 9999 )
Cycle 1 Day 1	15500 ( 0.9 )	14186 ( 13.0 )	4260 ( 36.5 )
Cycle 2 Day 1	16497 ( 2.6 )	19669 ( 7.9 )	19338 ( 11.6 )

Notes
[13] - Patients analyzed in each category: N=3, N=3, N=2
[14] - Patients analyzed in each category: N=0, N=6, N=5. Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: AUC of Plasma N-Desmethyl Enzalutamide: Segment 1

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End point title

AUC of Plasma N-Desmethyl Enzalutamide: Segment 1 ^[15]

End point description

AUC0-24 calculated using linear up and log down method. The PK-Evaluable Population included all patients who received active study treatment and had measurable plasma concentration of study treatment at any time point.

End point type

Secondary

End point timeframe

Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2 ^[16]	3 ^[17]	7 ^[18]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day -1 lead-in	143300 ( 9999 )	121320 ( 26.1 )	9999 ( 9999 )
Cycle 1 Day 1	9999 ( 9999 )	146225 ( 21.0 )	717 ( 9999 )
Cycle 2 Day 1	180628 ( 21.5 )	181855 ( 7.8 )	146580 ( 42.7 )

Notes
[16] - Patients analyzed in each category: N=1, N=0, N=2. Missing values are indicated by "9999".
[17] - Patients analyzed in each category: N=2, N=2, N=2
[18] - Patients analyzed in each category: N=0, N=1, N=5. Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Cmax of Plasma N-Desmethyl Enzalutamide: Segment 1

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End point title

Cmax of Plasma N-Desmethyl Enzalutamide: Segment 1 ^[19]

End point description

End point type

Secondary

End point timeframe

Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1.

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2	3 ^[20]	7 ^[21]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 Lead-in	7835 ( 14.3 )	5812 ( 12.6 )	9999 ( 9999 )
Cycle 1 Day 1	8570 ( 18.3 )	7074 ( 20.4 )	112 ( 1152.2 )
Cycle 2 Day 1	7760 ( 21.2 )	7996 ( 6.8 )	6742 ( 46.1 )

Notes
[20] - Patients analyzed in each category: N=3, N=3, N=2
[21] - Patients analyzed in each category: N=0, N=6, N=5. Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: AUC of Plasma Enzalutamide Carboxylic Acid: Segment 1

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End point title

AUC of Plasma Enzalutamide Carboxylic Acid: Segment 1 ^[22]

End point description

End point type

Secondary

End point timeframe

Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2 ^[23]	3 ^[24]	7 ^[25]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day -1 lead-in	19108 ( 9999 )	34493 ( 9999 )	9999 ( 9999 )
Cycle 1 Day 1	125786 ( 9999 )	52471 ( 26.3 )	1287 ( 9999 )
Cycle 2 Day 1	80970 ( 219.0 )	52579 ( 23.1 )	63388 ( 93.3 )

Notes
[23] - Patients analyzed in each category: N=1, N=1, N=2. Missing values are indicated by "9999".
[24] - Patients analyzed in each category: N=1, N=3, N=2. Missing values are indicated by "9999".
[25] - Patients analyzed in each category: N=0, N=1, N=5. Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 1

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End point title

Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 1 ^[26]

End point description

End point type

Secondary

End point timeframe

Predose and at time intervals up to 24 hours postdose on Cycle 1 Day -1, Cycle 1 Day 1, and Cycle 2 Day 1

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 1 only.

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant
Number of subjects analysed	2	3 ^[27]	7 ^[28]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day -1 lead-in	2286 ( 121.4 )	1930 ( 39.5 )	9999 ( 9999 )
Cycle 1 Day 1	3181 ( 113.8 )	2554 ( 26.6 )	127 ( 180.0 )
Cycle 2 Day 1	3719 ( 235.9 )	2862 ( 31.6 )	3088 ( 88.0 )

Notes
[27] - Patients analyzed in each category: N=3, N=3, N=2
[28] - Patients analyzed in each category: N=0, N=6, N=5. Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: AUC of Plasma Exicorilant: Segment 2

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End point title

AUC of Plasma Exicorilant: Segment 2 ^[29]

End point description

AUC from time zero to 6 hours postdose (AUC0-6) calculated using linear up and log down method. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6. The PK-Evaluable Population included all patients who received active study treatment and had measurable plasma concentration of study treatment at any time point.

End point type

Secondary

End point timeframe

Predose and at time intervals up to 6 hours on Cycle 1 Day 15 (before dose escalation) and at 2 weeks after each dose escalation (Week 4 for escalation from 240 mg to 280 mg exicorilant and Week 6 for escalation from 280 mg to 320 mg exicorilant)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[30]	1 ^[31]	9 ^[32]	5 ^[33]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	1086 ( 43.4 )	511 ( 9999 )	1125 ( 56.1 )	1201 ( 77.0 )
After 240 to 280 mg dose escalation	974 ( 9999 )	9999 ( 9999 )	1424 ( 53.3 )	990 ( 33.2 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	1589 ( 38.8 )	1012 ( 48.3 )

Notes
[30] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[31] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[32] - Patients analyzed in each category: N=9, N=7, N=6
[33] - Patients analyzed in each category: N=5, N=4, N=4

No statistical analyses for this end point

Secondary: Cmax of Plasma Exicorilant: Segment 2

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End point title

Cmax of Plasma Exicorilant: Segment 2 ^[34]

End point description

Maximum observed concentration over the dosing interval. Patients in Arm B did not receive dose escalations, but they were sampled for pharmacokinetic analysis on the same time frame as the Arm A patients: Cycle 1 Day 15, Week 4, and Week 6. The PK-Evaluable Population included all patients who received active study treatment and had measurable plasma concentration of study treatment at any time point.

End point type

Secondary

End point timeframe

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[35]	1 ^[36]	9 ^[37]	5 ^[38]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	402 ( 34.7 )	157 ( 9999 )	418 ( 61.7 )	495 ( 80.7 )
After 240 to 280 mg dose escalation	247 ( 9999 )	9999 ( 9999 )	528 ( 58.6 )	398 ( 63.8 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	534 ( 56.8 )	374 ( 65.9 )

Notes
[35] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[36] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[37] - Patients analyzed in each category: N=9, N=9, N=6
[38] - Patients analyzed in each category: N=5, N=4, N=4

No statistical analyses for this end point

Secondary: AUC of Plasma Enzalutamide: Segment 2

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End point title

AUC of Plasma Enzalutamide: Segment 2 ^[39]

End point description

End point type

Secondary

End point timeframe

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[40]	1 ^[41]	9 ^[42]	5 ^[43]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	93894 ( 27.5 )	90563 ( 9999 )	98157 ( 26.1 )	95735 ( 8.5 )
After 240 to 280 mg dose escalation	150022 ( 9999 )	9999 ( 9999 )	102373 ( 20.3 )	96684 ( 17.6 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	111632 ( 12.4 )	95653 ( 11.8 )

Notes
[40] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[41] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[42] - Patients analyzed in each category: N=9, N=6, N=6
[43] - Patients analyzed in each category: N=4, N=3, N=3

No statistical analyses for this end point

Secondary: Cmax of Plasma Enzalutamide: Segment 2

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End point title

Cmax of Plasma Enzalutamide: Segment 2 ^[44]

End point description

End point type

Secondary

End point timeframe

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[45]	1 ^[46]	9 ^[47]	5 ^[48]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	17609 ( 28.3 )	16800 ( 9999 )	18004 ( 25.6 )	18440 ( 15.2 )
After 240 to 280 mg dose escalation	27000 ( 9999 )	9999 ( 9999 )	18899 ( 17.9 )	18408 ( 22.8 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	20235 ( 13.2 )	18157 ( 17.0 )

Notes
[45] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[46] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[47] - Patients analyzed in each category: N=9, N=6, N=6
[48] - Patients analyzed in each category: N=4, N=3, N=3

No statistical analyses for this end point

Secondary: AUC of Plasma N-Desmethyl Enzalutamide: Segment 2

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End point title

AUC of Plasma N-Desmethyl Enzalutamide: Segment 2 ^[49]

End point description

End point type

Secondary

End point timeframe

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[50]	1 ^[51]	9 ^[52]	5 ^[53]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	67872 ( 7.0 )	34131 ( 9999 )	50752 ( 20.6 )	49744 ( 21.0 )
After 240 to 280 mg dose escalation	49995 ( 9999 )	9999 ( 9999 )	51977 ( 22.0 )	50353 ( 28.2 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	48255 ( 11.2 )	48411 ( 20.6 )

Notes
[50] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[51] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[52] - Patients analyzed in each category: N=9, N=6, N=6
[53] - Patients analyzed in each category: N=4, N=3, N=3

No statistical analyses for this end point

Secondary: Cmax of Plasma N-Desmethyl Enzalutamide: Segment 2

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End point title

Cmax of Plasma N-Desmethyl Enzalutamide: Segment 2 ^[54]

End point description

End point type

Secondary

End point timeframe

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[55]	1 ^[56]	9 ^[57]	5 ^[58]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	12448 ( 7.7 )	6520 ( 9999 )	9350 ( 22.8 )	10116 ( 24.3 )
After 240 to 280 mg dose escalation	8600 ( 9999 )	9999 ( 9999 )	9682 ( 20.4 )	9873 ( 28.4 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	8870 ( 13.4 )	9185 ( 23.8 )

Notes
[55] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[56] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[57] - Patients analyzed in each category: N=9, N=6, N=6
[58] - Patients analyzed in each category: N=4, N=3, N=3

No statistical analyses for this end point

Secondary: AUC of Plasma Enzalutamide Carboxylic Acid: Segment 2

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End point title

AUC of Plasma Enzalutamide Carboxylic Acid: Segment 2 ^[59]

End point description

End point type

Secondary

End point timeframe

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[60]	1 ^[61]	9 ^[62]	5 ^[63]
Units: ng-hr/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	25662 ( 55.7 )	14108 ( 9999 )	24863 ( 41.6 )	19310 ( 56.9 )
After 240 to 280 mg dose escalation	86613 ( 9999 )	9999 ( 9999 )	25995 ( 42.6 )	23393 ( 21.1 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	31814 ( 20.8 )	18047 ( 43.6 )

Notes
[60] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[61] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[62] - Patients analyzed in each category: N=9, N=6, N=6
[63] - Patients analyzed in each category: N=4, N=3, N=3

No statistical analyses for this end point

Secondary: Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 2

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End point title

Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 2 ^[64]

End point description

End point type

Secondary

End point timeframe

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point reports results for Segment 2 only.

End point values	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	5 ^[65]	1 ^[66]	9 ^[67]	5 ^[68]
Units: ng/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 15 before dose escalation	4693 ( 50.8 )	2480 ( 9999 )	4572 ( 40.8 )	3713 ( 58.3 )
After 240 to 280 mg dose escalation	15400 ( 9999 )	9999 ( 9999 )	4821 ( 43.1 )	4745 ( 15.1 )
After 280 to 320 mg dose escalation	9999 ( 9999 )	9999 ( 9999 )	6032 ( 24.8 )	3524 ( 44.1 )

Notes
[65] - Patients analyzed in each category: N=4, N=1, N=0. Missing values are indicated by "9999".
[66] - Patients analyzed in each category: N=1, N=0, N=0. Missing values are indicated by "9999".
[67] - Patients analyzed in each category: N=9, N=6, N=6
[68] - Patients analyzed in each category: N=4, N=3, N=3

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR)

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End point title

Objective Response Rate (ORR)

End point description

Confirmed ORR is defined as the proportion of patients with measurable disease at Baseline who achieved a complete regression (CR) or partial regression (PR) by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) / Modified Response Evaluation Criteria in Solid Tumors v1.1 (mRECIST) criteria, after confirmation. The Response-Evaluable (RE) Population included all patients who received ≥1 dose of the combination (exicorilant + enzalutamide) study treatment and had measurable disease at Baseline.

End point type

Secondary

End point timeframe

Up to 22 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2	0 ^[69]	5	3	0 ^[70]	6	1
Units: Patients	1		1	0		0	0

Notes
[69] - No patients with measurable disease at Baseline
[70] - No patients with measurable disease at Baseline

No statistical analyses for this end point

Secondary: Number of Patients With ≥50% Reduction in Prostate-Specific Antigen (PSA)

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End point title

Number of Patients With ≥50% Reduction in Prostate-Specific Antigen (PSA)

End point description

The Intent-to-treat (ITT) Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 39 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2	3	7	8	1	10	6
Units: Patients	2	0	3	0	0	1	0

No statistical analyses for this end point

Secondary: Time to PSA Progression

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End point title

Time to PSA Progression

End point description

Assess the time to PSA progression defined as the first occurrence of 50% or greater increase in PSA levels. Kaplan-Meier estimates of time to PSA progression were calculated as (earliest date of PSA progression or censoring - date of first study treatment + 1)/30.4375. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 39 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[71]	3 ^[72]	7 ^[73]	8 ^[74]	1 ^[75]	10 ^[76]	6 ^[77]
Units: months
median (confidence interval 95%)	9999 (9999 to 9999)	9999 (0.99 to 9999)	38.90 (0.99 to 9999)	1.43 (0.49 to 9999)	1.41 (-9999 to 9999)	1.41 (0.49 to 9999)	3.25 (0.95 to 9999)

Notes
[71] - Missing values are indicated by "9999".
[72] - Missing values are indicated by "9999".
[73] - Missing values are indicated by "9999".
[74] - Missing values are indicated by "9999".
[75] - Missing values are indicated by "9999".
[76] - Missing values are indicated by "9999".
[77] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Percentage of Patients Who Are Progression-Free by PSA Criteria at 4, 6, and 12 Months

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End point title

Percentage of Patients Who Are Progression-Free by PSA Criteria at 4, 6, and 12 Months

End point description

Assess the percentage of patients who are progression-free by PSA criteria, or death. PSA progression was defined as the first occurrence of 50% or greater increase in PSA levels. Values are Kaplan-Meier estimates of the patients progression free at the time points specified. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

4, 6, and 12 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[78]	3 ^[79]	7	8 ^[80]	1 ^[81]	10	6
Units: Percentage of patients
number (confidence interval 95%)
4 months	0 (-9999 to 9999)	9999 (9999 to 9999)	85.71 (33.41 to 97.86)	0 (-9999 to 9999)	0 (-9999 to 9999)	40.00 (12.27 to 67.02)	50.00 (11.09 to 80.37)
6 months	0 (-9999 to 9999)	9999 (9999 to 9999)	85.71 (33.41 to 97.86)	0 (-9999 to 9999)	0 (-9999 to 9999)	40.00 (12.27 to 67.02)	33.33 (4.61 to 67.56)
12 monthes	0 (-9999 to 9999)	9999 (9999 to 9999)	85.71 (33.41 to 97.86)	0 (-9999 to 9999)	0 (-9999 to 9999)	26.67 (4.76 to 56.34)	16.67 (0.77 to 51.68)

Notes
[78] - Missing values are indicated by "9999".
[79] - Missing values are indicated by "9999".
[80] - Missing values are indicated by "9999".
[81] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Time to First Symptomatic Skeletal Event (SSE)

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End point title

Time to First Symptomatic Skeletal Event (SSE)

End point description

Assess the time to first SSE defined as symptomatic fracture, radiation or surgery to bone, or spinal cord compression. Kaplan-Meier estimates of time to first SSE were calculated as (earliest date of SSE or censoring - date of first study treatment + 1)/30.4375. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 39 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[82]	3 ^[83]	7 ^[84]	8 ^[85]	1 ^[86]	10 ^[87]	6 ^[88]
Units: months
median (confidence interval 95%)	0 (-9999 to 9999)	9999 (2.83 to 9999)	9999 (25.79 to 9999)	9999 (9999 to 9999)	9999 (9999 to 9999)	9999 (9999 to 9999)	9999 (9999 to 9999)

Notes
[82] - Missing values are indicated by "9999".
[83] - Missing values are indicated by "9999".
[84] - Missing values are indicated by "9999".
[85] - Missing values are indicated by "9999".
[86] - Missing values are indicated by "9999".
[87] - Missing values are indicated by "9999".
[88] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Time to Progression by Radiographic Criteria

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End point title

Time to Progression by Radiographic Criteria

End point description

Assess radiographic progression free survival (PFS) defined as the time interval from first dose of study drug (exicorilant and/or enzalutamide) to the date when the first site of disease progression was found on computerized tomography (CT), magnetic resonance imaging (MRI), or radionucleotide bone scan per PCWG3/mRECIST v1.1, or death whichever occured first. The data values are Kaplan-Meier estimates. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 22 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[89]	3 ^[90]	7 ^[91]	8 ^[92]	1 ^[93]	10 ^[94]	6 ^[95]
Units: months
median (confidence interval 95%)	18.46 (-9999 to 9999)	1.81 (0.82 to 9999)	6.21 (0.49 to 9999)	5.55 (1.02 to 9999)	0 (-9999 to 9999)	5.08 (1.02 to 9999)	9999 (3.91 to 9999)

Notes
[89] - Missing values are indicated by "9999".
[90] - Missing values are indicated by "9999".
[91] - Missing values are indicated by "9999".
[92] - Missing values are indicated by "9999".
[93] - Missing values are indicated by "9999".
[94] - Missing values are indicated by "9999".
[95] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Percentage of Patients Who Are Progression-Free by Radiographic Criteria at 4, 6, and 12 Months

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End point title

Percentage of Patients Who Are Progression-Free by Radiographic Criteria at 4, 6, and 12 Months

End point description

Assess the percentage of patients who were progression-free by radiographic criteria per PCWG3/RECIST v1.1, or death whichever occured first. Values are Kaplan-Meier estimates of the patients progression free at the time points specified. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

4, 6, and 12 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[96]	3 ^[97]	7	8 ^[98]	1 ^[99]	10	6
Units: Percentage of patients
number (confidence interval 95%)
4 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	83.33 (27.31 to 97.47)	62.50 (14.19 to 89.31)	0 (-9999 to 9999)	66.67 (28.17 to 87.83)	83.33 (27.31 to 97.47)
6 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	62.50 (14.19 to 89.31)	0 (-9999 to 9999)	0 (-9999 to 9999)	33.33 (5.26 to 66.38)	62.50 (14.19 to 89.31)
12 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	41.67 (5.60 to 76.65)	0 (-9999 to 9999)	0 (-9999 to 9999)	33.33 (5.26 to 66.38)	62.50 (14.19 to 89.31)

Notes
[96] - Missing values are indicated by "9999".
[97] - Missing values are indicated by "9999".
[98] - Missing values are indicated by "9999".
[99] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Time to Progression by Clinical or Radiographic Criteria

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End point title

Time to Progression by Clinical or Radiographic Criteria

End point description

Determine PFS by clinical or radiographic criteria, or death, whichever occured first. Clinical progression was defined as treatment discontinuation due to disease progression by investigator assessment per PCWG3/mRECIST v1.1, or by PSA criteria. The data values are Kaplan-Meier estimates. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 22 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[100]	3 ^[101]	7 ^[102]	8 ^[103]	1 ^[104]	10 ^[105]	6 ^[106]
Units: months
median (confidence interval 95%)	18.46 (-9999 to 9999)	1.81 (0.82 to 9999)	6.21 (0.49 to 9999)	1.84 (0.99 to 9999)	0 (-9999 to 9999)	3.68 (1.02 to 9999)	9999 (3.91 to 9999)

Notes
[100] - Missing values are indicated by "9999".
[101] - Missing values are indicated by "9999".
[102] - Missing values are indicated by "9999".
[103] - Missing values are indicated by "9999".
[104] - Missing values are indicated by "9999".
[105] - Missing values are indicated by "9999".
[106] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Percentage of Patients Who Are Progression-Free by Clinical or Radiographic Criteria at 4, 6, and 12 Months

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End point title

Percentage of Patients Who Are Progression-Free by Clinical or Radiographic Criteria at 4, 6, and 12 Months

End point description

Assess the percentage of patients who were progression-free by clinical or radiographic measures at 4, 6, and 12 months. Values are Kaplan-Meier estimates of the patients progression free at the time points specified. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

4, 6, and 12 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2	3 ^[107]	7	8 ^[108]	1 ^[109]	10	6
Units: Percentage of patients
number (confidence interval 95%)
4 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	83.33 (27.31 to 97.47)	44.44 (6.62 to 78.49)	0 (-9999 to 9999)	50.00 (18.36 to 75.32)	83.33 (27.31 to 97.47)
6 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	62.50 (14.19 to 89.31)	0 (-9999 to 9999)	0 (-9999 to 9999)	33.33 (6.33 to 64.58)	62.50 (14.19 to 89.31)
12 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	41.67 (5.60 to 76.65)	0 (-9999 to 9999)	0 (-9999 to 9999)	33.33 (6.33 to 64.58)	62.50 (14.19 to 89.31)

Notes
[107] - Missing values are indicated by "9999".
[108] - Missing values are indicated by "9999".
[109] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Time to Progression by Clinical or Biochemical Criteria

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End point title

Time to Progression by Clinical or Biochemical Criteria

End point description

Determine PFS by clinical criteria or biochemical criteria (defined as treatment discontinuation due to clinical progression by investigator assessment, or by PSA criteria) PCWG3/mRECIST v1.1, or death whichever occurred first. The data values are Kaplan-Meier estimates. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 33 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[110]	3 ^[111]	7 ^[112]	8 ^[113]	1 ^[114]	10	6 ^[115]
Units: months
median (confidence interval 95%)	32.72 (-9999 to 9999)	5.85 (-9999 to 9999)	11.96 (3.68 to 9999)	3.55 (0.99 to 9999)	0 (-9999 to 9999)	6.77 (1.41 to 16.53)	9999 (4.86 to 9999)

Notes
[110] - Missing values are indicated by "9999."
[111] - Missing values are indicated by "9999."
[112] - Missing values are indicated by "9999."
[113] - Missing values are indicated by "9999."
[114] - Missing values are indicated by "9999."
[115] - Missing values are indicated by "9999."

No statistical analyses for this end point

Secondary: Percentage of Patients Who Are Progression-Free by Clinical or Biochemical Criteria at 4, 6, and 12 Months

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End point title

Percentage of Patients Who Are Progression-Free by Clinical or Biochemical Criteria at 4, 6, and 12 Months

End point description

Assess the percentage of patients who are progression-free by clinical or biochemical criteria (defined as treatment discontinuation due to clinical progression by investigator assessment or by PSA criteria) PCWG3/mRECIST v1.1, or death whichever occurred first at 4, 6, and 12 months. Values are Kaplan-Meier estimates of the patients progression free at the time points specified. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

4, 6, and 12 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2	3 ^[116]	7	8 ^[117]	1 ^[118]	10	6
Units: Percentage of patients
number (confidence interval 95%)
4 months	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	80.00 (20.38 to 96.92)	41.67 (1.12 to 84.31)	0 (-9999 to 9999)	70.00 (32.87 to 89.19)	100.0 (100.0 to 100.0)
6 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	60.00 (12.57 to 88.18)	9999 (9999 to 9999)	0 (-9999 to 9999)	58.33 (22.98 to 82.07)	75.00 (12.79 to 96.05)
12 months	100.0 (100.0 to 100.0)	0 (-9999 to 9999)	40.00 (5.20 to 75.28)	9999 (9999 to 9999)	0 (-9999 to 9999)	35.00 (8.48 to 63.98)	75.00 (12.79 to 96.05)

Notes
[116] - Missing values are indicated by "9999".
[117] - Missing values are indicated by "9999".
[118] - Missing values are indicated by "9999".

No statistical analyses for this end point

Secondary: Duration of Response (DOR)

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End point title

Duration of Response (DOR)

End point description

Determine the DOR as defined as the time from the first occurrence of a documented objective tumor response to the time of radiographic progression (per investigator using PCWG3/mRECIST v1.1 criteria) or death from any cause on study, whichever occurred first. DOR was calculated as (earliest date of progression, death, or censoring - date of first documented objective response +1)/30.4375. The data values are Kaplan-Meier estimates. The population analyzed included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment (ITT Population) and had an uncensored response (CR or PR).

End point type

Secondary

End point timeframe

Up to 11 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	0 ^[119]	0 ^[120]	1 ^[121]	0 ^[122]	0 ^[123]	0 ^[124]	0 ^[125]
Units: months
median (confidence interval 95%)	( to )	( to )	10.97 (-9999 to 9999)	( to )	( to )	( to )	( to )

Notes
[119] - No patients had an uncensored response.
[120] - No patients had an uncensored response.
[121] - Missing values are indicated by "9999".
[122] - No patients had an uncensored response.
[123] - No patients had an uncensored response.
[124] - No patients had an uncensored response.
[125] - No patients had an uncensored response.

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

Determine OS assessed as the time from the first dose of study drug (exicorilant and/or enzalutamide) to the date of death from any cause. The data values are Kaplan-Meier estimates. The ITT Population included all patients who received at least 1 dose of the combination (exicorilant + enzalutamide) study treatment.

End point type

Secondary

End point timeframe

Up to 52 months

End point values	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open-label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Number of subjects analysed	2 ^[126]	3 ^[127]	7 ^[128]	8 ^[129]	1 ^[130]	10 ^[131]	6 ^[132]
Units: months
median (confidence interval 95%)	32.72 (-9999 to 9999)	9999 (5.85 to 9999)	13.73 (4.63 to 9999)	9999 (3.55 to 9999)	9999 (9999 to 9999)	13.96 (4.47 to 9999)	17.23 (10.02 to 9999)

Notes
[126] - Missing values are indicated by "9999".
[127] - Missing values are indicated by "9999".
[128] - Missing values are indicated by "9999".
[129] - Missing values are indicated by "9999".
[130] - Missing values are indicated by "9999".
[131] - Missing values are indicated by "9999".
[132] - Missing values are indicated by "9999".

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Treatment-emergent adverse events were reported from randomization up to 27 months for Segment 1 and up to 19 months for Segment 2. All-cause mortality was reported from enrollment up to 52 months.

Adverse event reporting additional description

The population analyzed was the Safety Population, including all patients who received ≥1 dose of exicorilant.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

≥20.1

Reporting group title

Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant

Reporting group description

Reporting group title

Segment 1 (Open label) Cohort 2 - 280 mg Exicorilant

Reporting group description

Patients in this dose determination cohort received lead-in enzalutamide monotherapy once daily for 28 days. Patients then received combination treatment with twice-daily exicorilant 140 mg (total daily dose 280 mg) and enzalutamide once daily in 28-day dosing cycles.

Reporting group title

Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 240 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 280 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm A - Maximum Dose 320 mg Exicorilant

Reporting group description

Reporting group title

Segment 2: Arm B - 240 mg Exicorilant

Reporting group description

Patients in this dose determination arm received combination treatment with once-daily exicorilant 240 mg, enzalutamide once daily, and placebo in 28-day dosing cycles.

Serious adverse events	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)	2 / 8 (25.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)
number of deaths (all causes)	1	1	5	1	0	5	4
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Spinal fracture
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis acute
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urinary retention
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Sepsis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Segment 1 (Open-label) Cohort 1 - 360 mg Exicorilant	Segment 1 (Open label) Cohort 2 - 280 mg Exicorilant	Segment 1 (Open-label) Cohort 3 - 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 240 mg Exicorilant	Segment 2: Arm A - Maximum Dose 280 mg Exicorilant	Segment 2: Arm A - Maximum Dose 320 mg Exicorilant	Segment 2: Arm B - 240 mg Exicorilant
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 2 (100.00%)	3 / 3 (100.00%)	7 / 7 (100.00%)	8 / 8 (100.00%)	1 / 1 (100.00%)	10 / 10 (100.00%)	6 / 6 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	1	4	1	0	0	2
Deep vein thrombosis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Hot flush
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Hypotension
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Lymphoedema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 2 (100.00%)	0 / 3 (0.00%)	4 / 7 (57.14%)	5 / 8 (62.50%)	0 / 1 (0.00%)	6 / 10 (60.00%)	5 / 6 (83.33%)
occurrences all number	6	0	6	6	0	7	13
Non-cardiac chest pain
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	1	0	1	1
Oedema peripheral
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	2	1	0	0	0	1	0
Asthenia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	0	0	2
Malaise
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Peripheral swelling
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Chills
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Gait disturbance
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Influenza like illness
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Pyrexia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Reproductive system and breast disorders
Pelvic pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	3	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	3	0
Dyspnoea
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	3	0	0	0	1
Wheezing
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	1	0
Bronchospasm
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	0	0
Dyspnoea exertional
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0
Dysphonia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Lower respiratory tract congestion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Productive cough
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Pulmonary fibrosis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	1	0
Irritability
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Investigations
Lipase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	3 / 8 (37.50%)	1 / 1 (100.00%)	0 / 10 (0.00%)	4 / 6 (66.67%)
occurrences all number	0	0	0	5	1	0	4
Weight decreased
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	2	0	2	1	0	3	1
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	3 / 8 (37.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	3	3	0	0	1
Alanine aminotransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	3 / 8 (37.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	3	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 1 (100.00%)	1 / 10 (10.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	1	1	4
Aspartate aminotransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	2 / 8 (25.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	2	0	0	0
Amylase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	1	1
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Blood phosphorus decreased
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	0	0	0
Troponin increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Injury, poisoning and procedural complications
Incision site pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Fall
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Meniscus injury
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Radiation skin injury
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Spinal fracture
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Palpitations
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	1	0	2	0	0	1	1
Peripheral sensory neuropathy
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	1	0	1	1	0	1	2
Dizziness
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	0	0	1	1
Paraesthesia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)
occurrences all number	0	0	3	0	0	3	0
Dysgeusia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	0	0	1
Lethargy
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	0	0
Neuralgia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	2	0
Restless legs syndrome
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	0	0	1
Dysarthria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Dysmetria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Tremor
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Visual field defect
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Aphasia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Memory impairment
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Presyncope
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Sciatica
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Sensory disturbance
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 1 (100.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Syncope
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Transient ischaemic attack
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	1 / 1 (100.00%)	3 / 10 (30.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	3	1	3	2
Ear and labyrinth disorders
Ear congestion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Ear discomfort
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	0
Ear pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Eye disorders
Vision blurred
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	0	0	0	1
Dry eye
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Periorbital oedema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Visual acuity reduced
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	3 / 7 (42.86%)	2 / 8 (25.00%)	0 / 1 (0.00%)	4 / 10 (40.00%)	4 / 6 (66.67%)
occurrences all number	0	1	3	2	0	6	6
Abdominal pain
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 8 (12.50%)	1 / 1 (100.00%)	0 / 10 (0.00%)	3 / 6 (50.00%)
occurrences all number	2	1	1	1	2	0	4
Nausea
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 8 (12.50%)	1 / 1 (100.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)
occurrences all number	0	1	1	1	2	3	1
Diarrhoea
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	1	0
Dry mouth
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	1	0
Dyspepsia
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	1	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	0	0
Abdominal discomfort
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Dental caries
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Dental necrosis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	0	0
Flatulence
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 1 (100.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Vomiting
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 1 (100.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	3	0	0
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	1	1	1	0	0	1
Dry skin
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Skin lesion
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Milia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Nail disorder
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Nail ridging
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	2	1
Pollakiuria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	0
Proteinuria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	3	1
Nocturia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Micturition frequency decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Urinary hesitation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	2 / 2 (100.00%)	1 / 3 (33.33%)	4 / 7 (57.14%)	4 / 8 (50.00%)	1 / 1 (100.00%)	5 / 10 (50.00%)	5 / 6 (83.33%)
occurrences all number	2	1	7	7	3	7	8
Pain in extremity
subjects affected / exposed	2 / 2 (100.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	4 / 8 (50.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	8	1	0	7	0	4	1
Arthralgia
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	2 / 8 (25.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	3 / 6 (50.00%)
occurrences all number	0	1	2	2	0	1	3
Musculoskeletal chest pain
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)
occurrences all number	2	0	1	0	0	2	3
Musculoskeletal pain
subjects affected / exposed	2 / 2 (100.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	3 / 8 (37.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	4	0	0	3	0	0	0
Muscular weakness
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	0	1	1
Myalgia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	2	1
Flank pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	0	0	1
Neck pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	2	0	0	0
Pain in jaw
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Arthritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Groin pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Synovitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	1
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Furuncle
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0
COVID-19
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Laryngitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 2 (50.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 1 (0.00%)	3 / 10 (30.00%)	3 / 6 (50.00%)
occurrences all number	2	2	1	1	0	3	3
Hyperglycaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	0	0	1	1
Hypercalcaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	0	0	4
Hypoalbuminaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	1	1
Hypokalaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Gout
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Hypermagnesaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Hypophosphataemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

29 Sep 2017

– Modified the duration of enzalutamide lead-in for patients in the Dose Escalation Phase from 21 days to 28 days to ensure enzalutamide and its metabolites reach steady state on Cycle 1 Day -1 (Section 3.1) – Clarified that patients who have received prior 2nd generation anti-androgen and require urgent disease stabilization will be excluded from Dose Escalation and Cohort A and patients who require urgent disease stabilization will be excluded from Cohort B (Exclusion Criterion 3) – Revised the dose escalation rules (Table 6) to allow no more than a 50% dose increase after observing a related Grade 2 toxicity or DLT (Section 5.4) – Provided additional rationale to support the selection of the starting dose (Section 1.5.2) – Modified the definition of DLTs to include additional DLT criteria and to include only those toxicities that the investigator believes are possibly or probably related to the study drug (Section 5.5) – Revisions to Dose Modifications or Delays (Section 5.7) – As patients with CRPC may have received glucocorticoids previously, Inclusion Criterion 12 has been added to specify that patients receiving glucocorticoids greater than 2-weeks in duration within 6 months of study entry must have evidence of adequate adrenal function.

19 Dec 2017

- Section 5.6 has been amended to clarify that the recommended Phase 2 dose (RD) will always be less than or equal to the MTD. Thus, the recommended phase 2 dose will have a DLT rate of <33%, in keeping with the European definition of MTD. - Sections 8.1.2 and 8.2.2 have been amended to provide more detail for adverse event reporting for the following: 1) events due to progression, 2) documentation of death, including death due to progression of the cancer under study, and 3) reporting of serious adverse reactions deemed related to study drug. - Section 8.4 has been deleted to remove the statement that progression of the malignancy under study is not an AE, and therefore, not a serious adverse event (SAE) per se. Individual cases of progression deemed related to study drug will be recorded as adverse drug reactions; as consistent with the management of all AEs/SAEs that occur during the study.

09 Jan 2018

- Added clarification that initial dosing for the first 3 patients within a dose level (in Dose Escalation) will have a minimum of one day between Cycle 1 Day 1 for each patient. - Updated protocol and title to Phase 1/2a, and clarified the focus of the statistical methods on estimation of safety, tolerability and preliminary efficacy - Clarified that the number of patients in the Dose Escalation phase will depend on the number of dose levels assessed and the DLTs observed. Updated the study sample size section to state the statistical power of the study and the level of evidence in the data that will support further evaluation of the regimen in the clinical program. - Modified starting dose of CORT125281 to 180mg twice daily (360mg total daily dose) based upon the latest data from the ongoing Phase 1 study in healthy subjects. - Added 12 hour PK collection timepoints in the Dose Escalation and Dose Expansion cohorts to align with the latest data from the ongoing Phase 1 study in healthy subjects and the change to twice daily dosing of CORT125281. - Clarified the following: 1) Survival follow up period to continue every 4 months until 2 years from the date that the last patient enrolls in the study or until all patients have completed follow-up for radiographic disease progression (whichever is later). 2) Added dosing timing and windows along with instructions for missed doses. 3) Clarified procedures for collecting vital signs blood samples, and quality of life (FACT-P questionnaire). 4) Corrected collection of on-study radiographic tumor assessments to occur every 8 weeks from the first dose of CORT125281 or enzalutamide, whichever is earlier.

25 Jul 2018

- Refine criteria within Section 4: Study Population, specifically Inclusion Criteria 7, 8, and 9 and Exclusion Criterion 13, to select patients for whom protocol treatment is considered appropriate and avoid excluding patients appropriate for the study -Modify Section 4: Study Population to specify windows for restricted medications relative to the first dose of CORT125281, and not enzalutamide (Exclusion Criteria 1, 4, 5, 11) - Clarify eligibility for patients in the Dose Escalation Phase (Exclusion Criterion 3) such that patients who have received enzalutamide, but who did not experience disease progression during treatment, may be considered eligible - Modify collection of Pharmacogenomics sample from optional to mandatory, due to data indicative of a possible relevant genetic polymorphism in a drug metabolizing pathway in the ongoing Phase 1 study in healthy volunteers. Inclusion Criterion 10 has been added to align with this change. - Modify the excluded period (washout) for restricted concomitant medications, to allow patients time to transition to alternative therapies during the screening period, with consideration for concomitant medication half-life and the timing of pharmacokinetic assessments (Exclusion Criteria 1, 10, 11) - Modify Inclusion Criterion 13 such that patients with clinical evidence of adrenal insufficiency will require demonstration of adequate adrenal function to be eligible. For patients receiving systemic corticosteroids prior to enrolling in CORT125281-601, the window for which demonstration of adequate adrenal function is required has been decreased from within 6 months to within 3 months, to better capture patients most likely to have adrenal suppression from treatment with corticosteroids.

21 Feb 2020

- Added a double-blind portion (Segment 2) to the Dose-Determination Phase to determine the recommended dose (RD) for CORT125281 administered once daily (QD) under fed conditions - Revised the wording for the other portions of the study for clarity, upon addition of Dose-Determination Phase Segment 2: 1) Changed the name for the “Dose-Escalation Phase” to “Dose-Determination Phase” to better capture the intent for this part of the study and renamed the first portion of the Dose-Determination Phase (the open-label portion) as “Segment 1” now that there are 2 segments in the Dose-Determination Phase. 2) Changed the name for the Expansion Phase cohorts to avoid confusion with Arms A and B in Dose-Determination Phase Segment 2 and renamed “Cohort A” as the Abiraterone (Abi)-Resistant Cohort and renamed “Cohort B” as the Androgen-Receptor (AR)-Resistant Cohort. - Updated eligibility criteria to allow patients with metastatic castration-resistant prostate cancer (mCRPC) with rising prostate-specific antigen (PSA) - Added the 40-mg softgel capsule formulation of CORT125281 and the placebo capsule - Revised the text related to the interim safety analyses to reflect that the Data Review Committee (DRC) will evaluate data from Dose-Determination Phase Segment 2 after all patients have completed 3 cycles of treatment in this part of the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Phase 1/2a dose-escalation and expansion study to evaluate the safety, tolerability, and pharmacokinetics of CORT125281 with enzalutamide in patients with metastatic castration-resistant prostate cancer.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Patients With One or More Dose-Limiting Toxicity (DLT)

Primary: Number of Patients With One or More Dose-Limiting Toxicity (DLT)

Secondary: Number of Patients With 1 or More Treatment-Emergent Adverse Events

Secondary: Number of Patients With 1 or More Treatment-Emergent Adverse Events

Secondary: Area Under the Concentration Versus Time Curve (AUC) of Plasma Exicorilant: Segment 1

Secondary: Area Under the Concentration Versus Time Curve (AUC) of Plasma Exicorilant: Segment 1

Secondary: Maximum Observed Concentration (Cmax) of Plasma Exicorilant: Segment 1

Secondary: Maximum Observed Concentration (Cmax) of Plasma Exicorilant: Segment 1

Secondary: AUC of Plasma Enzalutamide: Segment 1

Secondary: AUC of Plasma Enzalutamide: Segment 1

Secondary: Cmax of Plasma Enzalutamide: Segment 1

Secondary: Cmax of Plasma Enzalutamide: Segment 1

Secondary: AUC of Plasma N-Desmethyl Enzalutamide: Segment 1

Secondary: AUC of Plasma N-Desmethyl Enzalutamide: Segment 1

Secondary: Cmax of Plasma N-Desmethyl Enzalutamide: Segment 1

Secondary: Cmax of Plasma N-Desmethyl Enzalutamide: Segment 1

Secondary: AUC of Plasma Enzalutamide Carboxylic Acid: Segment 1

Secondary: AUC of Plasma Enzalutamide Carboxylic Acid: Segment 1

Secondary: Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 1

Secondary: Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 1

Secondary: AUC of Plasma Exicorilant: Segment 2

Secondary: AUC of Plasma Exicorilant: Segment 2

Secondary: Cmax of Plasma Exicorilant: Segment 2

Secondary: Cmax of Plasma Exicorilant: Segment 2

Secondary: AUC of Plasma Enzalutamide: Segment 2

Secondary: AUC of Plasma Enzalutamide: Segment 2

Secondary: Cmax of Plasma Enzalutamide: Segment 2

Secondary: Cmax of Plasma Enzalutamide: Segment 2

Secondary: AUC of Plasma N-Desmethyl Enzalutamide: Segment 2

Secondary: AUC of Plasma N-Desmethyl Enzalutamide: Segment 2

Secondary: Cmax of Plasma N-Desmethyl Enzalutamide: Segment 2

Secondary: Cmax of Plasma N-Desmethyl Enzalutamide: Segment 2

Secondary: AUC of Plasma Enzalutamide Carboxylic Acid: Segment 2

Secondary: AUC of Plasma Enzalutamide Carboxylic Acid: Segment 2

Secondary: Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 2

Secondary: Cmax of Plasma Enzalutamide Carboxylic Acid: Segment 2

Secondary: Objective Response Rate (ORR)

Secondary: Objective Response Rate (ORR)

Secondary: Number of Patients With ≥50% Reduction in Prostate-Specific Antigen (PSA)

Secondary: Number of Patients With ≥50% Reduction in Prostate-Specific Antigen (PSA)

Secondary: Time to PSA Progression

Secondary: Time to PSA Progression

Secondary: Percentage of Patients Who Are Progression-Free by PSA Criteria at 4, 6, and 12 Months

Secondary: Percentage of Patients Who Are Progression-Free by PSA Criteria at 4, 6, and 12 Months

Secondary: Time to First Symptomatic Skeletal Event (SSE)

Secondary: Time to First Symptomatic Skeletal Event (SSE)

Secondary: Time to Progression by Radiographic Criteria

Secondary: Time to Progression by Radiographic Criteria

Secondary: Percentage of Patients Who Are Progression-Free by Radiographic Criteria at 4, 6, and 12 Months

Secondary: Percentage of Patients Who Are Progression-Free by Radiographic Criteria at 4, 6, and 12 Months

Secondary: Time to Progression by Clinical or Radiographic Criteria

Secondary: Time to Progression by Clinical or Radiographic Criteria

Secondary: Percentage of Patients Who Are Progression-Free by Clinical or Radiographic Criteria at 4, 6, and 12 Months

Secondary: Percentage of Patients Who Are Progression-Free by Clinical or Radiographic Criteria at 4, 6, and 12 Months

Secondary: Time to Progression by Clinical or Biochemical Criteria

Secondary: Time to Progression by Clinical or Biochemical Criteria

Secondary: Percentage of Patients Who Are Progression-Free by Clinical or Biochemical Criteria at 4, 6, and 12 Months

Secondary: Percentage of Patients Who Are Progression-Free by Clinical or Biochemical Criteria at 4, 6, and 12 Months

Secondary: Duration of Response (DOR)

Secondary: Duration of Response (DOR)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase 1/2a dose-escalation and expansion study to evaluate the safety, tolerability, and pharmacokinetics of CORT125281 with enzalutamide in patients with metastatic castration-resistant prostate cancer.