| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Endogenous Cushing¿s Syndrome |
| Sindrome di Cushing endogena |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cushing's syndrome caused by the body producing more cortisol than it needs |
| Sindrome di Cushing causata dalla produzione da parte del corpo di pi¿ cortisolo di quanto necessario |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
| MedDRA Classification |
| 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 | 10011657 |
| E.1.2 | Term | Cushings syndrome |
| E.1.2 | System Organ Class | 100000004860 |
|
| 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 | 10011657 |
| E.1.2 | Term | Cushings syndrome |
| E.1.2 | System Organ Class | 100000004860 |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the safety and efficacy of CORT125134 in patients with endogenous Cushing¿s syndrome. |
| Valutare la sicurezza di CORT125134 in pazienti affetti da sindrome di Cushing endogena. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the evidence of reduction in cortisol activity following treatment with CORT125134 in patients with endogenous Cushing¿s syndrome based on improvement in blood glucose control and/or blood pressure (BP). |
| Valutare l¿evidenza di riduzione dell¿attivit¿ del cortisolo in seguito al trattamento con CORT125134 in pazienti affetti da sindrome di Cushing endogena sulla base del miglioramento del controllo glicemico e/o della pressione arteriosa (PA). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Is a male or female adult, 18–80 years of age
2. Has a diagnosis of endogenous Cushing’s syndrome confirmed by:
At least two of the following test criteria (Nieman 2008):
•Urinary free cortisol above the upper limit of normal (ULN) (50.0 µg/24 h) in at least two, and up four, complete 24 hour collections within 3 weeks prior to Day 1 (baseline)
•Late-night salivary cortisol above the ULN (2 collections using a salivette) within 2 weeks prior to Day 1 (baseline)
•Lack of cortisol suppression (>1.8 µg/dL serum cortisol) on either 1 mg overnight or 2-mg 48 hour dexamethasone suppression testing during screening or within 12 weeks before the ICF is signed.
And
At least two of the following clinical signs and symptoms of Cushing’s syndrome:
•Facial characteristics of a Cushingoid appearance (moon facies, dorsocervical fat pad, plethora)
•Increased body weight or central obesity
•Proximal muscle weakness
•Low bone mass (dual energy X-ray absorptiometry [DXA] T < -1.0)
•Psychiatric symptoms (including depression or psychosis)
•Hirsutism and/or violaceous striae and/or acne
•Easy bruising
A patient with an adrenal lesion may alternatively qualify if there is
autonomous cortisol secretion based on dexamethasone suppression
testing (Fassnacht 2016) and supporting evidence of clinically significant
cortisol excess. Such a patient must have:
• Radiologically proven unilateral or bilateral adrenal disease (nodules,
hyperplasia)
• Lack of cortisol suppression (>5 µg/dL serum cortisol) on either 1-mg
overnight or 2-mg 48-hour dexamethasone suppression testing during
screening
• Low or suppressed ACTH (<10 pg/mL) to confirm ACTH-independency
• Presence of at least two comorbidities potentially related to cortisol
excess (eg, type 2 diabetes, hypertension, obesity, osteoporosis), of
which at least one is inadequately controlled by medical measures
3. Requires medical treatment of hypercortisolemia (i.e. those for whom surgery or radiation is contraindicated or has been refused)
Examples include, but are not limited to, patients with Cushing’s disease who are post-surgery and/or post-radiation for whom additional surgery is not recommended; de novo patients with Cushing’s disease who are not eligible for surgery due to comorbidities; and patients with ectopic ACTH-dependent Cushing’s syndrome in which the tumor cannot be localized or completely removed.
4. Meets at least one of the following criteria:
•Has type 2 diabetes mellitus as confirmed at screening visit with a fasting glucose >126 mg/dL and a 2-hour oral glucose tolerance test [oGTT] result for plasma glucose =200 mg/dL at 2 hours (Standards of Medical Care in Diabetes – 2015)
•Has impaired glucose tolerance (2-hour oGTT result for plasma glucose in the range of =140 mg/dL to <200 mg/dL) (Standards of Medical Care in Diabetes – 2015)
• Has hypertension (mean systolic BP of 130–170 mmHg and/or a mean diastolic BP of
85–110 mmHg) based on 24 hour ambulatory BP measurement (O’Brien 2013)
5. If taking antidiabetic medication, is on a stable dose (i.e. cannot start new medication or change dose within 4 weeks prior to the first dose of study drug)
6. If taking antihypertensive medication, is on a stable dose (i.e. cannot start new medication or change dose within 4 weeks prior to the screening ambulatory BP measurement)
7. Has potassium within the normal range (3.5–5.3 mEq/L) at screening or corrected to within the normal range by Day 1
8. Female patients of childbearing potential must be willing to use a highly effective method of contraception from 30 days prior to Day 1 until 30 days after the last dose of study drug. Male patients with a female partner must agree to 2 forms of contraception, one of which must be a double-barrier method, from Day 1 until 30 days after the last dose of study drug. Highly effective methods of contraception include abstinence, oral contraceptives combined with a barrier method, diaphragm with vaginal spermicide, intrauterine device, condom and partner using vaginal spermicide, and surgical sterilization (6 months post-surgery).
9. (Female patients): Has a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline (Day 1)
10. Has a life expectancy of at least 6 months
11. Is able to participate in the study for up to 22 weeks in Group 1 and 26 weeks in Group 2, including returning to the investigative site to fulfill the safety and efficacy evaluations outlined in the protocol
12. Is able to read and understand the consent form and communicate with the study staff
13. Provides written consent to participate in the study prior to any study procedures and understands that he/she is free to withdraw from the study at any time
|
1.Adulto di sesso maschile o femminile, di età compresa tra i 18 e gli 80 anni
2.Diagnosi di sindrome di Cushing endogena confermata da:
Almeno due dei seguenti criteri di analisi (Nieman 2008):
•Cortisolo urinario libero sopra il limite superiore della norma (LSN) (50,0 µg/24 h) in almeno due, e fino a quattro, raccolte complete di 24 ore effettuate nelle 3 settimane precedenti il Giorno 1 (basale)
•Cortisolo salivare notturno superiore a LSN (2 raccolte tramite dispositivo Salivette) nelle 2 settimane precedenti il Giorno 1 (basale)
•Mancata soppressione del cortisolo (> 1,8 µg/dl di cortisolo sierico) rilevata mediante test di soppressione con desametasone 1 mg in una notte o 2 mg nelle 48 ore effettuato durante lo screening o entro 12 settimane prima della firma del consenso informato
E
Almeno due dei seguenti segni e sintomi clinici della sindrome di Cushing:
•Caratteristiche facciali di aspetto cushingoide (facies lunare, accumulo di adipe a livello dorso-cervicale, pletora)
•Aumento del peso corporeo o obesità centrale
• Debolezza dei muscoli prossimali
• Bassa massa ossea (T < -1,0 all’assorbimetria a raggi X a doppia energia [dual energy X-ray absorptiometry, DXA])
• Sintomi psichiatrici (tra cui depressione o psicosi)
• Irsutismo e/o strie violacee e/o acne
• Facilità a riportare ecchimosi
Un paziente con una lesione surrenale potrà in alternativa essere ritenuto idoneo all’arruolamento in presenza di secrezione autonoma di cortisolo al test di soppressione con desametasone (Fassnacht 2016) e di evidenze a sostegno di un ipercortisolismo clinicamente significativo. Un paziente di questo tipo dovrà presentare:
• Una patologia surrenalica monolaterale o bilaterale (noduli, iperplasia) confermata all’esame radiologico
• Assenza di soppressione del cortisolo (cortisolo sierico >5 µg/dl) al test di soppressione con desametasone 1 mg con dosaggio al mattino seguente o 2 mg con dosaggio dopo 48 ore, eseguito durante lo screening
• Soppressione o basso livello di ACTH (<10 pg/ml) a conferma di ACTH-indipendenza.
• Presenza di almeno due patologie potenzialmente correlate all’ipercortisolismo (per es. diabete tipo 2, ipertensione, obesità, osteoporosi), di cui almeno una non adeguatamente controllata da misure mediche
3.Necessità di trattamento medico per ipercortisolemia (ossia, pazienti per i quali la chirurgia o la radioterapia è controindicata o è stata rifiutata)
Possibili esempi includono, a titolo non esaustivo, i pazienti con malattia di Cushing in fase post-chirurgica e/o post-radioterapica per i quali non sia raccomandato un ulteriore intervento chirurgico; pazienti con sindrome di Cushing de novo non idonei alla chirurgia per la presenza di comorbilità; e pazienti con sindrome di Cushing ectopica ACTH-dipendente nei quali il tumore non sia localizzabile o asportabile.
4. Presenza di almeno uno dei seguenti criteri:
• Diabete mellito di tipo 2 confermato alla visita di screening da una glicemia a digiuno > 126 mg/dl e da un risultato del test orale di tolleranza al glucosio di 2 ore (oral glucose tolerance test, oGTT) relativo al glucosio plasmatico = 200 mg/dl a 2 ore (Standards of Medical Care in Diabetes – 2015)
• Alterata tolleranza al glucosio (risultato del test oGTT di 2 ore relativo al glucosio plasmatico nell’intervallo = 140 mg/dl – < 200 mg/dl)
• Ipertensione (PA sistolica media di 130–170 mmHg e/o PA diastolica media di 85-110 mmHg) in base a una misurazione ambulatoriale della PA nelle 24 ore
5. Assunzione di una dose stabile, se il paziente è in terapia antidiabetica (ossia, non può iniziare un nuovo farmaco o modificare la dose nelle 4 settimane precedenti la prima dose del farmaco in studio)
6. Assunzione di una dose stabile, se il paziente è in terapia antipertensiva (ossia, non può iniziare un nuovo farmaco o modificare la dose nelle 4 settimane precedenti la misurazione ambulatoriale della PA).
7. Potassio nei limiti della norma (3,5–5,3 mEq/l) allo screening o corretto fino a rientrare nell’intervallo della norma entro il Giorno 1
8.8. Le pazienti di sesso femminile potenzialmente fertili devono essere disposte a utilizzare un metodo contraccettivo altamente efficace a partire dai 30 giorni precedenti il Giorno 1 fino ai 30 giorni successivi all’ultima dose di farmaco in studio. I pazienti di sesso maschile con una partner femminile devono acconsentire a utilizzare 2 metodi contraccettivi, uno dei quali deve essere un metodo di doppia barriera, dal Giorno 1 fino ai 30 giorni successivi all’ultima dose di farmaco in studio. I metodi contraccettivi altamente efficaci includono astinenza, contraccettivi orali associati a un metodo di barriera, diaframma con spermicida vaginale, dispositivo intrauterino, profilattico e partner che utilizza uno spermicida vaginale, e sterilizzazione chirurgica (= 6 mesi dall’intervento chirurgico)
Causa limite caratteri, per l'elenco completo si prega di fare riferimento alla versione in Inglese
|
|
| E.4 | Principal exclusion criteria |
1. Has a non-endogenous source of hypercortisolemia
2. Has pseudo-Cushing's syndrome. Patients with known or suspected
pseudo-Cushing's syndrome based on medical history (such as patients
with severe obesity, major depression, or a history of alcoholism) should
undergo a dexamethasone-CRH/DDAVP stimulation test (Yanovski 1993,
Giraldi 2007, Yanovski 1998) to rule-in or rule-out this possibility.
3. Has uncontrolled, clinically significant hypothyroidism or
hyperthyroidism
4. Has poorly controlled hypertension, defined as systolic BP >170
mmHg or diastolic BP >110 mmHg at screening
5. Has Stage 4 renal failure (ie, glomerular filtration rate =29 mL/min)
6. Has elevated total bilirubin >1.5×ULN or elevated alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) >3×ULN
7. For patients with diabetes or abnormal oGTT at screening: Has
glycated hemoglobin (HbA1c) of >12% within 3 months of first dose of
study drug
8. Has a screening hemoglobin level of <9 g/dL
9. Has a clinically significant electrocardiogram (ECG) abnormality at
screening, which, in the opinion of the Investigator, will make the
patient an unsuitable candidate for the study
10. Has a confirmed screening QTcF interval >450 ms for males and
>470 ms for females (using Fridericia's correction) in the presence of a
normal QRS interval (QRS <120 ms) or a history of additional risk
factors for torsades de pointes
11. Is currently receiving chemotherapy for a tumor related to Cushing's
syndrome
12. Had radiation therapy for Cushing's syndrome-related tumor within 1
year of screening period
13. Is planning surgery or radiation therapy for Cushing's syndromerelated
tumor during the study
14. Has used or plans to use any of the following treatments for
Cushing's syndrome, as specified:
•Adrenostatic medications: metyrapone, ketoconazole, fluconazole,
aminoglutethimide, or etomidate from 4 weeks prior to baseline (Day 1)
through the follow-up visit
•Adrenolytic medications:
oIn Group 1, any patients taking mitotane
oIn Group 2 only, patients with adrenocortical carcinomas taking
mitotane whose dose has not been stable for at least 2 months prior to
baseline (Day 1) or in whom increases in the mitotane dosage are
expected through the end of dosing
•Neuromodulator drugs that act at the hypothalamic-pituitary level:
serotonin antagonists (cyproheptadine, ketanserin, retanserin),
dopamine agonists (bromocriptine, cabergoline), gamma-aminobutyric
acid agonists (sodium valproate), and somatostatin receptor ligands
(octreotide long-acting release [LAR], pasireotide LAR, lanreotide) from
8 weeks before baseline (Day 1) through the follow-up visit. Use of
short-acting somatostatin analogs (octreotide, pasireotide) from 4
weeks prior to baseline (Day 1) through the follow-up visit.
•Mifepristone, from 6 weeks before baseline (Day 1) through the followup
visit
15. Has started or increased (or plans to start or increase) the dose of an
antidepressant medication (eg, selective serotonin reuptake inhibitors or
tricyclic compound) from 6 weeks before baseline (Day 1) through the end of the study dosing period
16. Has started or increased (or plans to start or increase) the dose of a
lipid-lowering drug from 4 weeks before baseline (Day 1) through the
follow-up visit
17. Is lactating
18. Has an acute or unstable medical problem that could be aggravated
by treatment with the investigational study drug
19. Has a history of hypersensitivity or severe reaction to the study drug,
to a similar class of drug, or to the study drug's excipients
20. Has taken any investigational drug within 30 days before baseline
(Day 1), or within a period of less than five times the drug's half life,
whichever is longer
21. In the Investigator's opinion, should not participate in the study or
may not be capable of following the study schedule
22. Has known HIV or hepatitis B or C infection
23. Is a family member of one of the Sponsor's employees, the
Investigator, or the site staff directly working on the study |
1. Presenza di fonte non endogena di ipercortisolemia
2. Sindrome di pseudo-Cushing. I pazienti con sindrome di pseudo-Cushing nota o sospetta sulla base dell’anamnesi (come pazienti con grave obesità, depressione maggiore o storia di alcolismo) devono essere sottoposti al test di stimolazione con desametasone-CRH/DDAVP (Yanovski 1993, Giraldi 2007, Yanovski 1998) per escludere o confermare tale possibilità.
3. Ipotiroidismo o ipertiroidismo non controllato e clinicamente significativo
4. Ipertensione non adeguatamente controllata, definita da un valore di PA sistolica > 170 mmHg o un valore di PA diastolica > 110 mmHg allo screening
5. Insufficienza renale di grado = 4 (ossia, velocità di filtrazione glomerulare = 29 ml/min)
6. Livelli elevati di bilirubina totale (> 1,5×LSN), di alanina aminotransferasi (ALT) o di aspartato aminotransferasi (AST), con valori > 3×LSN
7. Emoglobina glicata (HbA1c) allo screening > 12 %
8. Livello di emoglobina allo screening < 9 g/dl
9. Anomalia clinicamente significativa dell’elettrocardiogramma (ECG) allo screening che, secondo il parere dello Sperimentatore, renderebbe il paziente un candidato non idoneo allo studio
10. Intervallo QTcF confermato allo screening > 450 ms per gli uomini e > 470 ms per le donne (utilizzando la correzione di Fridericia) in presenza di un intervallo QRS normale (QRS < 120 ms) o di anamnesi di fattori di rischio supplementari per la torsione di punta
11. Trattamento chemioterapico in corso per un tumore legato alla sindrome di Cushing
12. Radioterapia per un tumore legato alla sindrome di Cushing nei 3 anni precedenti il periodo di screening
13. Chirurgia o radioterapia programmata durante lo studio per un tumore legato alla sindrome di Cushing
14. Utilizzo passato o previsto di uno dei seguenti trattamenti per la sindrome di Cushing, come indicato:
• Farmaci adrenostatici: metirapone, ketoconazolo, fluconazolo, aminoglutetimide o etomidato a partire dalle 4 settimane precedenti il basale (Giorno 1) fino alla visita di follow-up
• Farmaci adrenolitici:
o Nel Gruppo 1, qualsiasi paziente in terapia con mitotano
o Nel solo Gruppo 2, pazienti con carcinoma adrenocorticale in terapia con mitotano a una dose non stabile da almeno 2 mesi prima del basale (Giorno 1) o nei quali si preveda un incremento del dosaggio di mitotano fino alla fine della somministrazione
Farmaci neuromodulatori che agiscono a livello dell’asse ipotalamo-ipofisi: antagonisti della serotonina (ciproeptadina, ketanserina, retanserina), agonisti della dopamina (bromocriptina, cabergolina), agonisti dell’acido gamma-aminobutirrico (sodio valproato) e ligandi del recettore della somatostatina (octreotide a lento rilascio [long-acting release, LAR], pasireotide LAR, lanreotide) da 8 settimane prima del basale (Giorno 1) fino alla visita di follow-up. Utilizzo di analoghi della somatostatina a breve durata d’azione (octreotide, pasireotide) dalle 4 settimane precedenti il basale (Giorno 1) fino alla visita di follow-up.
• Mifepristone, dalle 6 settimane precedenti il basale (Giorno 1) fino alla visita di follow-up
15. Inizio dell’assunzione o incremento della dose (effettivo o programmato) di un farmaco antidepressivo (per es. inibitori selettivi della ricaptazione della serotonina o composto triciclico) dalle 6 settimane precedenti il basale (Giorno 1) fino al termine del periodo di somministrazione dello studio
16. Inizio dell’assunzione o incremento della dose (effettivo o programmato) di un farmaco ipolipidemizzante dalle 4 settimane precedenti il basale (Giorno 1) fino alla visita di follow-up
17. Allattamento al seno
18. Presenza di un problema medico acuto o instabile che potrebbe essere aggravato dal trattamento con il farmaco in studio sperimentale
19. Anamnesi di ipersensibilità o grave reazione al farmaco in studio, a una classe di farmaci simile o agli eccipienti del farmaco in studio
20. Assunzione di un qualsiasi farmaco sperimentale nei 30 giorni precedenti il basale (Giorno 1) o in un periodo cinque volte inferiore all’emivita del farmaco, a seconda di quale periodo sia il più lungo.
21. Inopportunità o possibile incapacità del paziente di partecipare allo studio o di attenersi allo schema di somministrazione, secondo il parere dello Sperimentatore
22. Nota infezione da HIV o da epatite B o C
23. Essere un familiare di uno dei dipendenti dello Sponsor, dello Sperimentatore o del personale del centro direttamente impegnato nello studio
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Oral glucose tolerance test (oGTT) (impaired glucose tolerance/diabetes subgroup only) •Ambulatory BP measurement (hypertension subgroup only) Pharmacokinetics: •Blood levels of CORT125134 and metabolites Safety: •Physical examination findings, vital signs, ECG results, pregnancy tests, clinical laboratory test results (hematology and chemistry panels), adverse events (AEs), and concomitant medications |
| Oral glucose tolerance test (oGTT) (impaired glucose tolerance/diabetes subgroup only) •Ambulatory BP measurement (hypertension subgroup only) Pharmacokinetics: •Blood levels of CORT125134 and metabolites Safety: •Physical examination findings, vital signs, ECG results, pregnancy tests, clinical laboratory test results (hematology and chemistry panels), adverse events (AEs), and concomitant medications |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
•oGTT all at screening. Type2 diabetes/impaired glucose tolerance subgroup, at baseline(D1) & wks 4, 8, 12/early termination (ET) for Group 1 & wks 4,8,12, & 16/ET for Group 2
•Ambulatory BP for all at screening. For hypertension subgroup baseline, wks 2, 4, 6, 8, 10, and 12/ET for Group 1 & wks 2, 4, 6, 8, 10, 12, 14, and 16/ET for Group 2.
• For Group 1, PK measured predose & 1, 2, 4, 6, and 8 hrs postdose at wks 2,6, and 10 , & predose only at wks 4, 8, and 12/early termination. Group 2, Pharmacokinetics measured predose & 1, 2, 4, 6, and 8 hours postdose at wks 2,6, 10, and 14, & predose only at wks 4,8,12, and 16/ET.
•Safety assessments at screening, baseline(D1); wks 2, 4, 6, 8, 10, & 12/ET for Group 1 & wks 2, 4, 6, 8, 10, 12, 14, & 16/ET for Group 2; & fup visit |
•oGTT all at screening. Type2 diabetes/impaired glucose tolerance subgroup, at baseline(D1) & wks 4, 8, 12/early termination (ET) for Group 1 & wks 4,8,12, & 16/ET for Group 2
•Ambulatory BP for all at screening. For hypertension subgroup baseline, wks 2, 4, 6, 8, 10, and 12/ET for Group 1 & wks 2, 4, 6, 8, 10, 12, 14, and 16/ET for Group 2.
• For Group 1, PK measured predose & 1, 2, 4, 6, and 8 hrs postdose at wks 2,6, and 10 , & predose only at wks 4, 8, and 12/early termination. Group 2, Pharmacokinetics measured predose & 1, 2, 4, 6, and 8 hours postdose at wks 2,6, 10, and 14, & predose only at wks 4,8,12, and 16/ET.
•Safety assessments at screening, baseline(D1); wks 2, 4, 6, 8, 10, & 12/ET for Group 1 & wks 2, 4, 6, 8, 10, 12, 14, & 16/ET for Group 2; & fup visit |
|
| E.5.2 | Secondary end point(s) |
| Exploratory efficacy assessments ¿Physician¿s Global Assessment ¿HbA1c ¿Fructosamine ¿Adiponectin ¿24-hour urinary free cortisol (UFC) with creatinine ¿Late-night salivary cortisol ¿Body weight, waist circumference ¿Beck Depression Inventory (BDI-II), Trail Making Test, CushingQoL ¿Lipid panel ¿Sit-to-stand test ¿Sex hormone levels ¿Menstrual cycle characterization (premenopausal women not on hormonal birth control) ¿Coagulation tests ¿FKBP5 test ¿Bone markers (serum bone alkaline phosphatase, osteocalcin, urine N telopeptides of type 1 collagen [NTx], calcium from 24-hour UFC) ¿Hypothalamic-pituitary-adrenal (HPA) axis markers, including plasma ACTH and serum cortisol concentrations ¿ACTH precursors (for EAS patients only) ¿High-sensitivity C-reactive protein concentrations ¿24-hour urine calcium and sodium ¿Insulin-like growth factor (IGF-1) ¿Thyroid function tests |
| Exploratory efficacy assessments ¿Physician¿s Global Assessment ¿HbA1c ¿Fructosamine ¿Adiponectin ¿24-hour urinary free cortisol (UFC) with creatinine ¿Late-night salivary cortisol ¿Body weight, waist circumference ¿Beck Depression Inventory (BDI-II), Trail Making Test, CushingQoL ¿Lipid panel ¿Sit-to-stand test ¿Sex hormone levels ¿Menstrual cycle characterization (premenopausal women not on hormonal birth control) ¿Coagulation tests ¿FKBP5 test ¿Bone markers (serum bone alkaline phosphatase, osteocalcin, urine N telopeptides of type 1 collagen [NTx], calcium from 24-hour UFC) ¿Hypothalamic-pituitary-adrenal (HPA) axis markers, including plasma ACTH and serum cortisol concentrations ¿ACTH precursors (for EAS patients only) ¿High-sensitivity C-reactive protein concentrations ¿24-hour urine calcium and sodium ¿Insulin-like growth factor (IGF-1) ¿Thyroid function tests |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At screening, baseline, Weeks 2, 4, 6, 8, 10, 12/ET, for Group 2; and follow-up visit |
| At screening, baseline, Weeks 2, 4, 6, 8, 10, 12/ET, for Group 2; and follow-up visit |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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