E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity and pre-diabetes |
Obesità e pre-diabete |
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E.1.1.1 | Medical condition in easily understood language |
A medical condition characterized by excessive accumulation of body fat and blood glucose level above the normal value, but not yet in the diabetic range |
Condizione medica caratterizzata da un eccessivo accumulo di grasso corporeo e livelli di glucosio nel sangue superiori alla norma, ma non ancora nel range del diabete |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10036481 |
E.1.2 | Term | Pre-diabetes |
E.1.2 | System Organ Class | 100000004861 |
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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 | 10065542 |
E.1.2 | Term | Prediabetes |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to explore whether ladarixin may improve insulin sensitivity in patients with pre-diabetes eligible to bariatric surgery due to obesity. The safety of ladarixin in the specific clinical setting will be also evaluated. |
L'obiettivo principale è esplorare se ladarixin può migliorare la sensibilità all'insulina nei pazienti con pre-diabete idonei alla chirurgia bariatrica a causa dell'obesità. Verrà inoltre valutata la sicurezza di ladarixin nello specifico contesto clinico. |
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E.2.2 | Secondary objectives of the trial |
not applicable |
non applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients aged 30-65 years, inclusive; - Body Mass Index (BMI) >35 kg/m2; - Presence of pre-diabetes (fasting glucose 100-125 mg/dL, inclusive; HbA1c 5.7-6.5%, inclusive); - Eligible to bariatric surgery as per any other criteria dictated by the Surgery Units; - Patients who have given written informed consent prior of any study-related procedure not part of standard medical care; - Patients able to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations. |
- Pazienti maschi e femmine di età compresa tra 30 e 65 anni inclusi; - Indice di massa corporea (BMI) >35 kg/m2; - Presenza di pre-diabete (glucosio a digiuno 100-125 mg/dL, incluso; HbA1c 5,7-6,5%, incluso); - Idoneo alla chirurgia bariatrica secondo eventuali altri criteri dettati dalle Unità di Chirurgia; - Pazienti che hanno fornito il consenso informato scritto prima di qualsiasi procedura correlata allo studio non facente parte delle cure mediche standard; - Pazienti in grado di attenersi a tutte le procedure del protocollo per la durata dello studio, comprese le visite di follow-up e gli esami programmati. |
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E.4 | Principal exclusion criteria |
- Moderate to severe renal impairment (creatinine clearance (CLcr) <60 mL/min); - Hepatic dysfunction (defined by increased ALT/AST >3 x upper limit of normal and increased total bilirubin >3 mg/dL [>51.3 µmol/L]); - Hypoalbuminemia (serum albumin <3 g/dL); - QTcF >470 msec; - History of any past or current clinically significant cardiovascular disease/abnormality; - Known hypersensitivity to non-steroidal antiinflammatory drugs; - Presence of any other clinical condition/disease that the PI believes might compromise patient’s safety or otherwise confound study outcome; - Patients on treatment with phenytoin, warfarin, sulphanylurea hypoglycemics and high dose of amitriptyline (>50 mg/day); - Previous (within 2 weeks prior to randomization) treatment with any medications known to influence glucose tolerance - Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males). |
- Insufficienza renale da moderata a grave (clearance della creatinina (CrCl) <60 mL/min); - Disfunzione epatica (ALT/AST superiori di tre volte il limite superiore di normalità e bilirubina totale >3 mg/dL [>51.3 µmol/L]); - Ipoalbuminemia (albumina serica < 3 g/dL); - QTcF >470 msec; - Storia di qualsiasi malattia/anormalità cardiovascolare clinicamente significativa passata o attuale; - nota ipersensibilità ai farmaci antinfiammatori non steroidei; - Presenza di qualsiasi altra condizione/malattia clinica che l'IP ritiene possa compromettere la sicurezza del paziente o altrimenti confondere i risultati dello studio; - Pazienti in trattamento con farmaco con stretta finestra terapeutica metabolizzati dal citocromo CYP2C9; - Pazienti in trattamento con con insulina o qualsiasi ipoglicemizzante orale o altro farmaco di cui sia nota la capacità di influenzare la tolleranza al glucosio; - Saranno anche escluse le donne in stato di gravidanza o durante l’allattamento e donne e uomini che non desiderano utilizzare un metodo efficace di contraccezione. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints: • Insulin Sensitivity Index-Matsuda (ISI-M) from 3h-(OGTT) • Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) • C-peptide AUC from 3h-OGTT • Proinsulin : C-peptide ratio • Proportion of patients with Impaired Glucose Tolerance (IGT) • Hormones (adipokine, incretines, etc.) • Inflammatory chemokines/cytokines and CRP • Gut (faeces) microbiome/microbiota “Diversity” • Abdominal obesity (waist and waist/hip circumference) • Adipocyte characterization (exploratory endpoint) Safety Endpoints: • Blood pressure and heart rate • Safety laboratory tests [haematology (haematocrit, haemoglobin, red blood cells, platelets, white blood cells, differential white blood cells count) and clinical chemistry (sodium, potassium, serum creatinine, serum albumin, total bilirubin, ALT, AST)] • Incidence of Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
Endpoint di efficacia: • Indice di sensibilità all'insulina secondo Matsuda (ISI-M) derivato dall’OGTT di 3 ore • Modello di valutazione all'omeostasi della resistenza all'insulina (HOMA-IR) • AUC del C-peptide derivato dall'OGTT di 3 ore • Rapporto Proinsulina: C-peptide • Proporzione di pazienti con alterata tolleranza al glucosio (IGT) • Ormoni (adipochine, incretine, ecc) • Chemochine/citochine infiammatorie e CRP • Profilo del microbioma/microbiota intestinale (feci) • Obesità addominale (circonferenza alla vita e rapporto circonferenza vita/fianchi) • Caratterizzazione degli adipociti (variabile di tipo esplorativo) Endpoint di sicurezza: • Pressione sanguigna e frequenza cardiaca • “Parametri ematici di sicurezza” [ematologia (ematocrito, emoglobina, eritrociti, piastrine, globuli bianchi, conta differenziale dei globuli bianchi) e biochimica (sodio, potassio, creatinina serica, albumina serica, bilirubina totale, ALT, AST)]; • Incidenza degli eventi avversi emergenti dal trattamento (TEAE) e degli eventi avversi gravi emergenti dal trattamento (TESAE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All efficacy endpoints will be measured at the follow-up visit (day 71-75), ideally within 2 days of the last dose of IMP. The surgery will be performed within one week of the end of the treatment. All safety endpoints will be assessed at the end of treatment cycle 1, within 7 days of the end of the cycle, and at follow-up (day 71-75), ideally within 2 days of the last dose of the study treatment. TEAEs / TESAEs will be recorded during the study, starting on Day 1 of treatment. |
Tutti gli endpoint di efficacia saranno misurati alla visita di follow-up (giorno 71-75), idealmente entro 2 giorni dall’ultima dose di IMP. L’intervento chirurgico verrà effettuato entro una settimana dal termine del trattamento. Tutti gli endpoint di sicurezza saranno valutati alla fine del ciclo1 di trattamento, entro 7 giorni dalla fine del ciclo, e al follow-up, (giorno 71-75), idealmente entro 2 giorni dall’ultima dose del trattamento in studio. TEAEs/TESAEs verranno registrati durante lo studio, partendo dal Giorno 1 di trattamento. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
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 | No |
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
|
For the purpose of this trial, the end of study is defined as the date of the last procedure (date of bariatric surgery) of the last patient. |
Ai fini di questa sperimentazione, la fine dello studio è definita come la data dell'ultima procedura (data della chirurgia bariatrica) dell'ultimo paziente. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |