Clinical Trials Register

Summary
EudraCT Number:	2017-000244-18
Sponsor's Protocol Code Number:	BAY1128688/17472
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-08-21
Trial results	View 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

2017-000244-18

A.3

Full title of the trial

A randomized, placebo-controlled, double-blind, parallel-group, multicenter,
exploratory dose-response study to assess the efficacy and safety
of different oral doses of BAY 1128688 in women with symptomatic
endometriosis over a 12-week treatment period

Studio randomizzato, controllato con placebo, in doppio cieco, per gruppi paralleli, multicentrico, esplorativo dose-risposta volto alla valutazione dell'efficacia e della sicurezza di diverse dosi orali di BAY 1128688 in donne affette da endometriosi sintomatica, per un periodo di trattamento di 12 settimane

A.3.1

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

A study to test whether study drug BAY1128688 brings pain relief to
women with endometriosis and if so to get a first idea which dose(s) work
best.

Studio esplorativo di risposta alle dosi in pazienti affette da endometriosi

A.3.2

Name or abbreviated title of the trial where available

Akrendo 1

A.4.1

Sponsor's protocol code number

BAY1128688/17472

A.5.4

Other Identifiers

Name:

Akrendo 1

Number:

BAY1128688/17472

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	BAYER HEALTHCARE AG
B.1.3.4	Country	Germany
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	Bayer AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer AG
B.5.2	Functional name of contact point	Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	13342 Berlino
B.5.3.2	Town/ city	Berlino
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	004930300139003
B.5.5	Fax number	004930300139003
B.5.6	E-mail	clinical-trials-contact@bayer.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	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	BAY 1128688 coated tablet 3 mg
D.3.2	Product code	BAY1128688 coated tblt 3mg 001
D.3.4	Pharmaceutical form	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	1428988-21-9
D.3.9.2	Current sponsor code	BAY 1128688
D.3.9.3	Other descriptive name	BAY 1128688
D.3.9.4	EV Substance Code	SUB130437
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	3
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	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	BAY1128688 coated tablet 10 mg
D.3.2	Product code	BAY1128688 coated tbl 10mg 110
D.3.4	Pharmaceutical form	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	1428988-21-9
D.3.9.2	Current sponsor code	BAY 1138688
D.3.9.3	Other descriptive name	BAY 1138688
D.3.9.4	EV Substance Code	SUB130437
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	10
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	BAY 1128688 coated tablet 30 mg
D.3.2	Product code	BAY1128688 coated tbl 30mg 302
D.3.4	Pharmaceutical form	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	1428988-21-9
D.3.9.2	Current sponsor code	BAY 1128688
D.3.9.3	Other descriptive name	BAY 1128688
D.3.9.4	EV Substance Code	SUB130437
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	30
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	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	BAY1128688 coated tablet 60 mg
D.3.2	Product code	BAY1128688 coated tbl 60mg 602
D.3.4	Pharmaceutical form	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	1428988-21-9
D.3.9.2	Current sponsor code	BAY 1128688
D.3.9.3	Other descriptive name	BAY 1128688
D.3.9.4	EV Substance Code	SUB130437
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	60
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Endometriosis

Endometriosi

E.1.1.1

Medical condition in easily understood language

Endometriosis is a disease of young women (before menopause); women
suffer from pain in the pelvic/ lower abdominal area and difficulties to
become pregnant

L’endometriosi è una malattia che interessa le giovani donne (prima della menopausa); le donne manifestano dolore nell’area pelvica/addominale bassa e difficoltà nell’iniziare una gravidanza

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10014778
E.1.2	Term	Endometriosis
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10014788
E.1.2	Term	Endometriosis related pain
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Explore the dose response relationship of different doses of BAY
1128688 compared to placebo in the treatment of endometriosis-related
symptoms over a 12-week treatment period

Analisi del rapporto dose-risposta di varie dosi di BAY 1128688 rispetto al placebo nel trattamento dei sintomi associati all’endometriosi in un periodo di trattamento di 12 settimane

E.2.2

Secondary objectives of the trial

Assessment of safety and tolerability of BAY 1128688 over a 12-week
treatment period

L’endometriosi è una malattia che interessa le giovani donne (prima della menopausa); le donne manifestano dolore nell’area pelvica/addominale bassa e difficoltà nell’iniziare una gravidanza

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Women of at least 18 years of age at the time of signing of informed consent
- Diagnosis of endometriosis confirmed by at least one of the two criteria:
-- visually-confirmed (by surgery or clinical inspection) within the last 10 years
-- imaging-confirmed within the last 12 months
- Symptoms of moderate to severe pelvic pain which will be assessed over a period of 28 days
- Good general health
- Willingness to use only ibuprofen as rescue pain medication for endometriosis-associated pelvic pain
- Willingness to use non-hormonal barrier method for contraception (here spermicide-coated condoms) from screening visit until the end of
the study (maximum 280 days) and to refrain from using hormonal contraception

- Donne di almeno 18 anni al momento della firma del consenso informato
- Diagnosi di endometriosi confermata da almeno uno di questi due criteri:
- endometriosi confermata visivamente (dalla chirurgia o ispezione clinica) nei 10 anni precedenti;
- endometriosi confermata da un esame di diagnostica per immagini nei 12 mesi precedenti allo screening
- Sintomi di dolore pelvico da moderato a grave che saranno valutati per un periodo di 28 giorni
- Disponibilità a utilizzare soltanto l’ibuprofene come antidolorifico di emergenza per il dolore pelvico associato all’endometriosi
-Disponibilità a utilizzare un metodo contraccettivo non ormonale a barriera (in questo caso preservativi ricoperti di spermicida) dalla visita di screening fino alla fine dello studio (massimo 280 giorni) ed evitare di utilizzare contraccettivi ormonali.
- Buono stato di salute generale

E.4

Principal exclusion criteria

- Pregnancy or lactation (less than three months since delivery, abortion, or lactation before start of treatment) AND no wish for pregnancy during the study
- Altered bilirubin metabolism and liver function at Visit 1
- Requirement to use pain medications for reasons other than endometriosis
- Contraindications to using ibuprofen and/or contraindications to using the study drug
- Signs of hyperandrogenism
- Absence of menstrual cycles and/or abnormal vaginal/genital bleeding
- History of hysterectomy, tubal-ligation or bilateral ovariectomy
- Any diseases, conditions or edications/treatments that might intefere with the conduct of the study or the interpretation of the results

- Gravidanza o allattamento (meno di tre mesi dal parto, dall’aborto o dall’allattamento prima dell’inizio del trattamento) E nessun desiderio di gravidanza nel corso dello studio
- Alterazione del metabolismo della bilirubina e della funzionalità epatica alla Visita 1
- Necessità di utilizzare antidolorifici per motivi diversi dall’endometriosi
- Controindicazioni all’utilizzo di ibuprofene e/o controindicazioni all’utilizzo del farmaco in studio
- Segni di iperandrogenismo
- Assenza del ciclo mestruale e/o sanguinamento vaginale/genitale anomalo
- Anamnesi di isterectomia, legatura delle tube o ovariectomia bilaterale
- Qualsiasi malattia, condizione o medicinale/trattamento che possa interferire con la conduzione dello studio o l’interpretazione dei risultati

E.5 End points

E.5.1

Primary end point(s)

Absolute change in mean pain of the 7 days with worst EAPP from
baseline (last 28 days before SoT visit) to end of treatment (last 28 days
of the treatment period, Day 57 - 84) (measured on the NRS by item 1 of
the ESD).

Variazione assoluta del dolore medio nei 7 giorni con il peggiore dolore associato all’endometriosi (EAPP) dal basale (ultimi 28 giorni prima della visita di inizio trattamento) alla fine del trattamento (ultimi 28 giorni del periodo di trattamento, giorni 57 - 84) (misurato sulla scala di valutazione numerica [NRS] con l’opzione 1 dell’ESD)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.5.2

Secondary end point(s)

The secondary safety variable is the incidence of treatment-emergent adverse events

La variabile di sicurezza secondaria è costituita dall’incidenza degli eventi avversi associati al trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

18 weeks

18 settimane

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

Yes

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Effects of BAY 1128688 on health-related quality of life

Gli effetti di BAY 1128688 sulla qualità della vita legata alla salute

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

100

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

LVLS

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

Number of subjects for this age range:

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

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

120

F.4.2.2

In the whole clinical trial

120

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

2017-12-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-12-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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