Clinical Trials Register

Summary
EudraCT Number:	2021-006289-19
Sponsor's Protocol Code Number:	D9720C00003
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-10-05
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-006289-19

A.3

Full title of the trial

A Multi-arm, Open-label Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD5305 in Combination with New Hormonal Agents in Patients with Metastatic Prostate Cancer (PETRANHA)

Studio di fase I/IIa, a bracci multipli, in aperto per valutare la sicurezza, la tollerabilità, la farmacocinetica, la farmacodinamica e l’efficacia preliminare di AZD5305 in combinazione con agenti ormonali di nuova generazione in pazienti con carcinoma prostatico metastatico (PETRANHA)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to assess safety, efficacy and pharmacokinetics of AZD5305 when given in combination with new hormonal agents in patients with Metastatic Prostate Cancer

Studio per valutare sicurezza, efficacia e farmacocinetica di AZD5305 quando somministrato in combinazione con nuovi agenti ormonali in pazienti con carcinoma prostatico metastatico

A.3.2

Name or abbreviated title of the trial where available

PETRANHA

A.4.1

Sponsor's protocol code number

D9720C00003

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05367440

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ASTRAZENECA AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	Non applicabile
B.5.3.2	Town/ city	Non applicabile
B.5.3.3	Post code	Non applicabile
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Nubeqa 300 mg compresse rivestite con film
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Darolutamide
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Darolutamide
D.3.9.1	CAS number	1297538-32-9
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	Darolutamide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Zytiga
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Abiraterone Acetate
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	abiraterone acetato
D.3.9.1	CAS number	154229-19-3
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	Abiraterone Acetate
D.3.9.4	EV Substance Code	SUB07361MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	-
D.3.2	Product code	[AZD5305]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	2589531-76-8
D.3.9.2	Current sponsor code	AZD5305
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.5 to 100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Zytiga
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Abiraterone Acetate
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	abiraterone acetato
D.3.9.1	CAS number	154229-19-3
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	Abiraterone Acetate
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xtandi
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe B.V.
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Enzalutamide
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ENZALUTAMIDE
D.3.9.1	CAS number	915087-33-1
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	Enzalutamide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic Prostate Cancer

Carcinoma prostatico metastatico

E.1.1.1

Medical condition in easily understood language

Cancer of prostate gland that spreads to different parts of body (metastatic) in men

Cancro della ghiandola prostatica che si diffonde in diverse parti del corpo (metastatico) negli uomini

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To assess the safety and tolerability of AZD5305 when given in combination with new hormonal agents (NHA) (enzalutamide, abiraterone acetate, or darolutamide) to patients with metastatic prostate cancer

- Valutare la sicurezza e la tollerabilità di AZD5305 quando somministrato in combinazione con nuovi agenti ormonali (NHA) (enzalutamide. abiraterone acetato o darolutamide) a pazienti con carcinoma prostatico metastatico

E.2.2

Secondary objectives of the trial

- To characterise the Pharmacokinetic (PK) of AZD5305 monotherapy in plasma following a single dose and/or at steady state after multiple dosing when given orally as monotherapy and in combination with an NHA
- To evaluate the effect of enzalutamide on the PK of AZD5305
- To assess the preliminary antitumour activity of AZD5305 in combination with an NHA
- To characterize the PK of enzalutamide in plasma at steady state when given orally in combination with AZD5305

- Caratterizzare la Farmacocinetica (PK) di AZD5305 in monoterapia nel plasma dopo una dose singola e/o allo stato costante dopo dosi multiple quando somministrato per via orale come monoterapia e in combinazione con un NHA
- Valutare l’effetto di enzalutamide sulla PK di AZD5305
- Valutare l’attività antitumorale preliminare di AZD5305 in combinazione con un NHA
- Caratterizzare la PK di enzalutamide nel plasma allo stato costante quando somministrato per via orale in combinazione con AZD5305

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age >= 18 at the time of screening.
• Histologically confirmed diagnosis of metastatic prostate cancer.
• Candidate for treatment with enzalutamide, abiraterone acetate, or darolutamide with documented current evidence of metastatic prostate cancer.
• Surgically or medically castrated.
• Patients with Metastatic Castrate Resistant Prostate Cancer (mCRPC) or Metastatic Hormone Sensitive Prostate Cancer (mHSPC).
• Adequate organ and marrow function.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
• Life expectancy >= 16 weeks.
• Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 6 months after the last dose of study treatment .

For Patients Recruited Specifically to Tumour Pharmacodynamic Cohorts:
• Patients must have at least 1 tumour suitable for paired biopsies

- Età >=18 anni al momento dello screening
- Diagnosi istologicamente confermata di cancro alla prostata metastatico.
- Il candidato per il trattamento con enzalutamide, abiraterone acetate, o darolutamide con evidenza documentatata di cancro alla prostata metastatico.
- Castrazione chirurgica o medica.
- Pazienti con carcinoma prostatico metastatico resistente alla castrazione (mCRPC) o carcinoma prostatico metastatico sensibile agli ormoni (mHSPC).
- Adeguata funzionalità degli organi o del midollo
- Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 senza deterioramento nelle precedent 2 settimane.
- Aspettativa di vita >= 16 settimane.
- I pazienti maschi non sterilizzati che sono sessualmente attivi con una partner femminile potenzialmente fertile devono utilizzare un preservativo con spermicida dallo screening fino a circa 6 mesi dopo l’ultima dose di trattamento dello studio.

Per i pazienti reclutati specificamente nelle coorti farmacodinamiche tumorali:
- I pazienti devono avere almeno 1 tumore adatto a biopsie accoppiate.

E.4

Principal exclusion criteria

• Concomitant use of medications or herbal supplements that may involve severe drug-drug interactions with the study treatment.
• Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
• Treatment with any of the following:
a) Any investigational agents or study interventions from a previous clinical study within 5 half lives or 3 weeks (whichever is shorter) of the first dose of study treatment.
b) Any other anticancer treatment within the following time periods prior to the first dose of study treatment: (i) Cytotoxic and non-cytotoxic treatment: 3 weeks or 5 half-lives (whichever is shorter). (ii) Biological products including immuno-oncology agents: 4 weeks before enrolment.
c) Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.
• Any concurrent anticancer therapy or concurrent use of prohibited medications.
• Any previous treatment with a poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitor, Lu-PSMA, platinum chemotherapy, docetaxel (for mHSPC patients).

Please refer to protocol for a complete list.

- Uso concomitante di farmaci o integratori a base di erbe che possono comportare gravi interazioni farmaco-farmaco con il trattamento in studio.
- Uso concomitante di farmaci che notoriamente prolungano o accorciano il QT e che presentano un rischio noto di Torsades de Pointes.
- Trattamento con uno dei seguenti:
a) qualsiasi agente sperimentale o intervento in studio da un precedente studio clinico entro 5 emivite o 3 settimante (a seconda di quale sia il più breve) dalla prima dose del trattamento in studio
b) Qualsiasi altro trattamento antitumorale entro i seguenti periodi di tempo prima della prima dose di trattamento in studio: (i) Trattamento citotossico e non citotossico: 3 settimane o 5 emivite (a seconda di quale sia il più breve). (ii) Prodotti biologici inclusi agenti immuno-oncologici: 4 settimane prima dell'arruolamento.
c) Qualsiasi vaccino virale o batterico vivo entro 28 giorni dalla prima dose di trattamento dello studio.
- Qualsiasi terapia antitumorale concomitante o uso concomitante di farmaci vietati.
- Qualsiasi trattamento precedente con un inibitore della poli (adenosina difosfato-ribosio) polimerasi (PARP), Lu-PSMA, chemioterapia a base di platino, docetaxel (per i pazienti con mHSPC).

Si prega di fare riferimento al protocollo per un elenco completo.

E.5 End points

E.5.1

Primary end point(s)

AZD5305 in combination with NHA:
• Number of participants with adverse events/ serious adverse events
• Number of participants with Dose Limiting Toxicities (DLTs)
• Changes from baseline in laboratory findings, physical examination, ECOG performance status, ECGs, and vital signs

AZD5305 in combinazione con NHA:
- Numero di partecipanti con eventi avversi / aventi avversi seri
- Numero di partecipanti con tossicità dose-limitante (DLT)
- Variazioni rispetto al basale nei risultati di laboratorio, negli esami obiettivi, nello stato di validità ECOG, negli ECG e nei segni vitali

E.5.1.1

Timepoint(s) of evaluation of this end point

Length of cycle: Cycle 0: 7 days; Cycle 1 onwards (28 days each).
AZD5305 in combination with NHA:
• From Screening (day -28) up to post treatment follow-up (28 days after last dose)
• From Cycle 0 Day 1 to end of cycle 1 (day 28)
• From Screening (day -28) up to post treatment follow-up (28 days after last dose)

Durata del ciclo: Ciclo 0: 7 giorni; Ciclo 1 e successivi (28 giorni ciascuno).
AZD5305 in combinazione con NHA:
• Dallo screening (giorno -28) fino al follow-up post trattamento (28 giorni dopo l’ultima dose)
• Dal ciclo 0 giorno 1 alla fine del ciclo 1 (giorno 28)
• Dallo screening (giorno -28) fino al follow-up post trattamento (28 giorni dopo l’ultima dose)

E.5.2

Secondary end point(s)

PK Parameters:
(AZD5305 monotherapy):
• Area Under the concentration Curve (AUC) of AZD5305
• Maximum plasma concentration (Cmax) of AZD5305
• Time to maximum concentration (Tmax) of AZD5305;

(AZD5305 in combination with NHA):
• AUC of AZD5305
• Cmax of AZD5305
• tmax of AZD5305;

Efficacy parameters:
• Objective response rate (ORR)
• Duration of response (DoR)
• Time to response (TTR)
• Radiographic progression-free survival (rPFS)
• Percentage change in target lesion size
• Proportion of participants with > 50% PSA decrease;

PK parameters of Enzalutamide in combination with AZD5305:
• AUC of enzalutamide
• Cmax of enzalutamide
• tmax of enzalutamide

Parametri PK:
(AZD5305 in monoterapia):
• Area sotto la curva concentrazione (AUC) di AZD5305
• Concentrazione plasmatica massima (Cmax) di AZD5305
• Tempo alla concentrazione massima (Tmax) di AZD5305;

(AZD5305 in combinazione con NHA):
• AUC di AZD5305
• Cmax di AZD5305
• Tmax di AZD5305;

Parametri di efficacia:
• Tasso di risposta obiettiva (ORR)
• Durata della risposta (DoR)
• Tempo alla risposta (TTR)
• Sopravvivenza libera da progressione radiografica (rPFS)
• Variazione percentuale nella dimensione della lesione target
• Percentuale di partecipanti con riduzione > 50% del PSA;

Parametri PK di Enzalutamide in combinazione con AZD5305:
• AUC di enzalutamide
• Cmax di enzalutamide
• Tmax di enzalutamide

E.5.2.1

Timepoint(s) of evaluation of this end point

PK Parameters:
(AZD5305 monotherapy):
At Cycle 0 Day 7

(AZD5305 in combination with NHA):
AZD5305 with enzalutamide:
At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1;

AZD5305 with abiraterone acetate, and AZD5305 with darolutamide:
At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1;

Efficacy parameters:
From Screening (Day -28) to confirmed disease progression;

PK parameters of Enzalutamide in combination with AZD5305:
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1.

Parametri PK:
(AZD5305 in monoterapia):
Al Ciclo 0 giorno 7

(AZD5305 in combinazione con NHA):
AZD5305 con enzalutamide:
Al Ciclo 1 giorno 1, Ciclo 1 giorno 22, Ciclo 2 giorno 1, Ciclo 2 giorno 2, Ciclo 2 giorno 8, e Ciclo 3 giorno 1;

AZD5305 con abiraterone acetato, e AZD5305 con darolutamide:
Al Ciclo 1 giorno 1, Ciclo 1 giorno 15 e Ciclo 2 giorno 1;

Parametri di efficacia:
Dallo screening (giorno -28) alla conferma della progressione della malattia;

Parametri PK di enzalutamide in combinazione con AZD5305:
Al Ciclo 1 giorno 22, Ciclo 2 giorno 1, Ciclo 2 giorno 2, Ciclo 2 giorno 8 e Ciclo 3 giorno 1.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Drug-drug interaction

Interazione farmaco-farmaco

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

United States

Italy

United Kingdom

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as completing the last expected visit/contact of the last patient undergoing the study.

La fine dello studio è definita come il completamento dell'ultima visita/contatto previsto dell'ultimo paziente nello studio.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

140

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Nessuno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-30

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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