Clinical Trials Register

Summary
EudraCT Number:	2021-003177-58
Sponsor's Protocol Code Number:	SPIOMET4HEALTH
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-03-31
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

Spain - AEMPS

A.2

EudraCT number

2021-003177-58

A.3

Full title of the trial

A Phase II, randomised, multi-centric, multi-national clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone & Metformin (SPIOMET) for adolescent girls and young adult women (AYAs) with polycystic ovary syndrome (PCOS)

Ensayo clínico de fase II, aleatorizado, multicéntrico y multinacional para evaluar la
eficacia, la tolerabilidad y la seguridad de una combinación de dosis fijas de
espironolactona, pioglitazona y metformina (SPIOMET) para adolescentes y mujeres
adultas jóvenes con síndrome de ovario poliquístico (SOP).

A.3.1

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

A.4.1

Sponsor's protocol code number

SPIOMET4HEALTH

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/150/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fundació Sant Joan de Déu (FSJD)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	European Commission
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundació Sant Joan de Déu (FSJD)
B.5.2	Functional name of contact point	Coordinator
B.5.3	Address:
B.5.3.1	Street Address	Esplugués de Llobregat
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08950
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34936009751
B.5.5	Fax number	+34936009771
B.5.6	E-mail	lourdes.ibanez@sjd.es

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	SPIOMET
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	Spironolactone
D.3.9.1	CAS number	52-01-7
D.3.9.4	EV Substance Code	SUB10631MIG
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pioglitazone
D.3.9.1	CAS number	111025-46-8
D.3.9.4	EV Substance Code	SUB09857MIG
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	7.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Metformin
D.3.9.1	CAS number	657-24-9
D.3.9.4	EV Substance Code	SUB08831MIG
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	850
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	SPIO
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	Spironolactone
D.3.9.1	CAS number	52-01-7
D.3.9.4	EV Substance Code	SUB10631MIG
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pioglitazone
D.3.9.1	CAS number	111025-46-8
D.3.9.4	EV Substance Code	SUB09857MIG
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	7.5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	PIO
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	Pioglitazone
D.3.9.1	CAS number	111025-46-8
D.3.9.4	EV Substance Code	SUB09857MIG
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	7.5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Film-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

Polycystic Ovary Syndrome (PCOS)

Síndrome de ovario poliquístico (SOP)

E.1.1.1

Medical condition in easily understood language

Polycystic Ovary Syndrome (PCOS)

Síndrome de ovario poliquístico (SOP)

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10065161
E.1.2	Term	Polycystic ovarian syndrome
E.1.2	System Organ Class	100000004872

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 test the efficacy of SPIOMET in normalising ovulation in adolescents and young adult women with PCOS.

Comprobar la eficacia de SPIOMET para normalizar la tasa de
ovulación en adolescentes y mujeres adultas jóvenes con SOP

E.2.2

Secondary objectives of the trial

To test the efficacy of SPIOMET in normalising the endocrine-metabolic status, body composition and abdominal fat distribution, on-treatment and post-treatment; to assess the safety of SPIOMET and the
adherence and subjective acceptability, and the quality of life of participating subjects.

Comprobar la eficacia de SPIOMET en la normalización del estado endocrino-metabólico, describir el perfil de seguridad del fármaco y evaluar la
adherencia, la aceptabilidad y la calidad de vida de las participantes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age range within the AYAs category (> 12.0 years and < or = 23.9 years at study start);
2. Gynaecological age of 2 years or more;
3. Clinical androgen excess, as defined by the presence of hirsutism (modified Ferriman-Gallwey score > or = 4) and/or inflammatory acne (Leeds scale) unresponsive to medications. The scarce normative data existing in adolescents suggest that an adult level of hirsutism is reached around 2 years after menarche;
4. Biochemical androgen excess, as defined by increased total testosterone (> o = 50 ng/dL), and/or a FAI higher than 3.5 [FAI, total testosterone (nmol/L) x 100/SHBG (nmol/L)], in the follicular phase of the cycle (days 3–7) or after 2 months of amenorrhea;
5. Menstrual irregularity, as defined by < or = 8 menses per year corresponding to an average intermenstrual time of > or =45 days;
6. Written informed consent obtained from the patient, or assent from the patient and consent by the parents or the legally acceptable representative if she is a minor

1. Rango de edad dentro de la categoría AYAs (> 12,0 años y < o = 23,9 años al inicio del estudio);
2. Edad ginecológica de 2 años o más;
3. Exceso clínico de andrógenos, definido por la presencia de hirsutismo (puntuación de Ferriman-Gallwey modificada > o = 4) y/o acné inflamatorio (escala de Leeds) que no responde a los medicamentos. Los escasos datos normativos existentes en adolescentes sugieren que el nivel de hirsutismo adulto se alcanza alrededor de los 2 años después de la menarquia;
4. Exceso bioquímico de andrógenos, definido por un aumento de la testosterona total (> o =50 ng/dL), y/o un IAF superior a 3,5 [IAF, testosterona total (nmol/L) x 100/SHBG (nmol/L)], en la fase folicular del ciclo (días 3-7) o tras 2 meses de amenorrea;
5. Irregularidad menstrual, definida por < o = 8 menstruaciones al año correspondientes a un tiempo intermenstrual medio de > o =45 días;
6. Consentimiento informado por escrito obtenido de la paciente, o asentimiento de la paciente y consentimiento de los padres o del representante legal si es menor de edad

E.4

Principal exclusion criteria

1. Class II obesity or morbid obesity (BMI of 35 kg/m2 or higher) according to published international standard charts for both adolescents and young women;
2. Underweight (BMI<18.5 kg/m2) and eating disorders (anorexia nervosa);
3. Anaemia or bleeding disorder;
4. Evidence of thyroid, liver, or kidney dysfunction; if the value for a specific variable is not within the normal range for the local lab, the assessment must be repeated. If the subsequent value is within the normal range, the patient can be included in the study. Patients diagnosed with subclinical hypothyroidism or autoimmune thyroiditis
can also be included if the condition is treated and the lab values of thyroid variables are within the normal range for the local lab;
5. Precocious puberty [breast development before age 8 yr and/or precocious menarche (menarche before age 10.0 yr);
6. Cushing syndrome;
7. Late-onset adrenal hyperplasia due to 21 hydroxylase deficiency [17-hydroxyprogesterone levels >200 ng/dL in the follicular phase of the cycle or after 2 mo of amenorrhea];
8. Hyperprolactinaemia (due to any cause included breast-feeding);
9. Glucose intolerance or diabetes mellitus;
10. Use of medications affecting gonadal or adrenal function, or carbohydrate or lipid metabolism in the previous three months (including OCs);
11. Gynaecological age < 2.0 years;
12. Positive pregnancy test;
13. Pregnancy risk (failure to guarantee the use of non-hormonal contraception in sexually active subjects).
14. Cardiac failure or history of cardiac failure.
15. Hypersensitivity to the study drugs or any of their excipients.
16. Addison disease.
17. Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis).
18. Diabetic pre-coma.
20. Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock.
21. Disease which may cause tissue hypoxia (especially acute disease or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock.
22. Acute alcohol intoxication, alcoholism.
23. Hyperkalaemia.
24. Concomitant use of eplerenone or other potassium sparing diuretics.
25. Concomitant use of other potassium conserving diuretics and potassium supplements should not be given routinely.
26. Current bladder cancer or a history of bladder cancer.
27. Non-investigated macroscopic haematuria.

1. Obesidad de clase II u obesidad mórbida (IMC de 35 kg/m2 o superior) según las tablas estándar internacionales publicadas tanto para adolescentes como para mujeres jóvenes;
2. Bajo peso (IMC<18,5 kg/m2) y trastornos alimentarios (anorexia nerviosa);
3. Anemia o trastorno hemorrágico;
4. Evidencia de disfunción tiroidea, hepática o renal; si el valor de una variable específica no está dentro del rango normal para el laboratorio local, la evaluación debe repetirse. Si el valor subsiguiente está dentro del normal, el paciente puede ser incluido en el estudio. Las pacientes diagnosticadas con hipotiroidismo subclínico o tiroiditis autoinmune también pueden ser incluidos si la condición es tratada y los valores de laboratorio de variables tiroideas están dentro del rango normal para el laboratorio local;
5. Pubertad precoz [desarrollo de las mamas antes de los 8 años y/o menarquia precoz (menarquia antes de los 10 años);
6. Síndrome de Cushing;
7. Hiperplasia suprarrenal de aparición tardía por deficiencia de 21-hidroxilasa [niveles de 17-hidroxiprogesterona
niveles >200 ng/dL en la fase folicular del ciclo o después de 2 meses de amenorrea];
8. Hiperprolactinemia (debida a cualquier causa, incluida la lactancia)
9. Intolerancia a la glucosa o diabetes mellitus;
10. Uso de medicamentos que afecten a la función gonadal o suprarrenal, o al metabolismo de los hidratos de carbono o de los lípidos en los tres meses anteriores (incluidos los AO);
11. Edad ginecológica < 2,0 años;
12. Prueba de embarazo positiva;
13. Riesgo de embarazo (no garantizar el uso de anticonceptivos no hormonales en sujetos sexualmente activos).
14. Insuficiencia cardíaca o antecedentes de insuficiencia cardíaca.
15. Hipersensibilidad a los fármacos del estudio o a cualquiera de sus excipientes.
16. Enfermedad de Addison.
17. Cualquier tipo de acidosis metabólica aguda (como acidosis láctica, cetoacidosis cetoacidosis diabética).
18. Precoma diabético.
20. Condiciones agudas con potencial para alterar la función renal como: deshidratación, infección grave, shock.
21. Enfermedad que pueda causar hipoxia tisular (especialmente enfermedad aguda o empeoramiento de una enfermedad crónica) como: insuficiencia cardíaca descompensada insuficiencia respiratoria, infarto de miocardio reciente, shock.
22. Intoxicación alcohólica aguda, alcoholismo.
23. Hiperpotasemia.
24. Uso concomitante de eplerenona u otros diuréticos ahorradores de potasio.
25. El uso concomitante de otros diuréticos conservadores de potasio y suplementos de potasio no debe administrarse de forma rutinaria.
26. Cáncer de vejiga actual o antecedentes de cáncer de vejiga.
27. Hematuria macroscópica no investigada.

E.5 End points

E.5.1

Primary end point(s)

On-treatment and post-treatment ovulation rate.

Tasa de ovulación durante y después del tratamiento

E.5.1.1

Timepoint(s) of evaluation of this end point

Following end of each two 12-week on-treatment periods (month 0-3 and month 9-12), and following the end of post-treatment period (month 12-15)

Al final de cada uno de los dos periodos de 12 semanas de tratamiento (mes 0-3 y mes 9-12), y al final del periodo de post-tratamiento (mes 12-15)

E.5.2

Secondary end point(s)

1. Clinical variables: hirsutism (modified Ferriman & Gallwey score), Acne (evaluated using the Leeds Acne Grading Scale), menstrual regularity (3,17)
2. Endocrine-metabolic variables:
• Circulating androgens: total testosterone, SHBG, free androgen index (FAI),
androstenedione;
• Lipids - total cholesterol, low-density lipoprotein (LDL-cholesterol), high-density lipoprotein
(HDL- cholesterol), triglycerides;
• Insulinaemia: fasting and 2 hours after a 75-gr oral glucose load [oral glucose tolerance test (oGTT). Estimation of insulin resistance from fasting insulin and glucose levels using the homeostasis model assessment (HOMA);
• Markers of inflammation & insulin sensitivity: ultra-sensitive C-reactive protein (us-CRP); growth-and- differentiation factor-15 (GDF15); high molecular weight adiponectin (HMW-adip), C-X-C motif chemokine ligand 14 (CXCL14) (69,81);
3. Epigenetic variable: circulating microRNA 451-a
(miR-451a) concentrations (88);
4. Imaging variables:
• Cardiovascular risk – cIMT (ultrasound);
• Body composition: dual-energy X-ray absorptiometry (DXA);
• Abdominal fat distribution (subcutaneous and
visceral) and hepatic fat (MRI);
5. Lifestyle assessment:
• Body composition, abdominal fat distribution (waist circumference, Waist to hip ratio (WHR), and hepatic fat by MRI) and weight status;
• Improvement of co-morbidities and health behaviour (SF-36, PCOSQ, modified self reported health
ehaviour in school-aged children questionnaire (HBSC-Q)
• Minimisation of adverse side effects (i.e., “Sick-Control-One-Fat-Food” (SCOFF) + Binge
Eating Disorder Screener 7 (BEDS-7) questionnaires to assess the risk of eating disorders; of risk confirmed, then, the EDE-Q will be used)
• Improvement of HRQoL;
6. Safety variables:
• Blood count, electrolyte panel, urea, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), creatinine, vitamin B12 and folic acid;
• Report of AEs;
7. Adherence and acceptability:
• Adherence will be calculated as the ratio between the number of tablets prescribed and dispensed for the period between hospital appointments and the number of tablets returned by the patient at the following appointment;
• Acceptability of the tablet by the study patients;
8. PROMs & HRQoL: generic (SF-36) and specific (PCOSQ) questionnaires

1. Variables clínicas:
• Hirsutismo (escala de Ferriman y Gallwey modificada),
• Regularidad menstrual
• Acné (evaluado mediante la escala de clasificación del acné de Leeds)
2. Variables endocrino-metabólicas:
• Andrógenos circulantes: testosterona total, globulina fijadora de hormonas sexuales (SHBG), índice de andrógenos libres (FAI), androstenediona
• Lípidos: colesterol total, lipoproteínas de baja densidad (LDL), lipoproteínas de alta densidad (HDL), triglicéridos
• Insulinemia: en ayunas y dos horas después de una carga de glucosa oral (prueba de tolerancia a la glucosa oral [oGTT]). Estimación de la
resistencia a la insulina a partir de los niveles de insulina y glucosa en ayunas mediante la evaluación del modelo homeostático de resistencia a la insulina (IR-HOMA)
• Marcadores de inflamación y sensibilidad a la insulina: proteína C reactiva ultrasensible (us-CRP); factor de crecimiento y diferenciación 15 (GDF15); adiponectina de alto peso molecular (HMW-adip), ligando de quimiocina con motivo C-X-C 14 (CXCL14)
3. Variable epigenética: concentraciones circulantes de MicroRNA 451a (miR-451a)
4. Variables de imagen:
• Riesgo cardiovascular; grosor íntima-media carotídeo (cIMT) (ecografía)
• Composición corporal: absorciometría de rayos X de doble energía (DXA)
• Distribución de la grasa abdominal (subcutánea y visceral) y de la grasa hepática (resonancia magnética, [IRM])
5. Evaluación del estilo de vida:
• Composición corporal, distribución de la grasa abdominal (perímetro de la cintura, relación cintura-cadera y grasa hepática por IRM) y estado del peso
• Mejora de las comorbilidades y de las conductas en materia de salud
• Reducción de los efectos secundarios adversos (por ejemplo, trastornos alimentarios)
• Mejora de la calidad de vida relacionada con la salud (CVRS)
6. Variables de seguridad:
• Recuento sanguíneo, panel de electrolitos, urea, alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), gamma glutamiltransferasa (GGT), creatinina, vitamina B12 y ácido fólico
• Informe de los eventos adversos (EA).
7. Adherencia y aceptabilidad:
• La adherencia, calculada como la relación entre el número de comprimidos prescritos y dispensados para el período entre las citas
hospitalarias y el número de comprimidos devueltos por la paciente en la siguiente cita.
• Aceptación del comprimido por parte de las pacientes del estudio.
8. Medidas según los resultados percibidos por la paciente (PROM) sobre la CVRS: encuesta genérica de salud de formulario corto 36 (SF-36) y
cuestionarios de calidad de vida relacionada con la salud y el SOP (PCOSQ).

E.5.2.1

Timepoint(s) of evaluation of this end point

As defined per protocol.

Según se define en el protocolo

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

E.6.7

Pharmacodynamic

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)

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

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

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

Turkey

E.8.7

Trial has a data monitoring committee

Yes

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

Última visita del último paciente

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

180

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

180

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

184

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

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

116

F.4.2

For a multinational trial

F.4.2.1

In the EEA

322

F.4.2.2

In the whole clinical trial

364

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

Ninugno

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

2022-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-03-25

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

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