Título: Estudio de fase 2b, aleatorizado, doble ciego y controlado con placebo para determinar el rango de dosis y evaluar la eficacia y seguridad de múltiples niveles de dosis de AZD8630 inhalado administrado una vez al día durante 12 semanas en adultos con asma no controlada con riesgo de exacerbaciones (LEVANTE)
Especialidad: Neumología
Código de protocolo: D6830C00003
Número EudraCT: 2024-514228-18-00
Promotor: Astra Zeneca
Investigador principal: Dr. Gustavo de Luiz
Más información:
CRO: IQVIA
Criterios de inclusión: Patient must be 18 to 80 years of age inclusive, at the time of signing the ICF
Pre-BD FEV1 40% at both Visit 1 and Visit 2.
A pre-BD/pre-study intervention dose FEV1 at Visit 2 that has not increased by 400 ml from the pre-BD FEV1 recorded at Visit 1.
Patient has documented evidence of any of the following: (a) A history of 1 severe exacerbation within the last 12 months and either: (i) FeNO 25 ppb at the screening and randomisation visits (Visits 1 and 2) (ii) Eosinophil count 150 cells/µL, recorded at any point in the 12 months up to and including the Screening Visit (local testing can be carried out to confirm eligibility if eosinophil count not available in medical records within the last 12 months). (b) A history of 2 severe exacerbations within 12 months of Visit 1. A severe exacerbation is defined as an episode of symptoms of asthma worsening that results in at least one of the following: OCS use for 3 consecutive days, inpatient ( 24 hours) hospitalisation for asthma or emergency room or equivalent visit for asthma that results in systemic CS use.
At least 80% compliance with usual asthma background medication during the run-in period based on the daily asthma ePROs.
Minimum 80% compliance with daily assessments. Compliance is defined as completing the daily ePROs and PEF measurements (morning and evening) at least 80% of the time during the 14-day period prior to the randomisation visit (minimum of 11 days) preceding Vi
Any patient at GINA step 5 (i.e. on high dose ICS plus LABA) for which an injectable biologic therapy for asthma is indicated (according to local prescribing guidance) must meet the following to be included Be unable or unwilling to receive an injectable biologic, or for whom such treatment is considered contraindicated or inappropriate in the opinion of the investigator. Documentation must be provided in the source records
BMI within the range 18-37 kg/m2 (inclusive) at the time of signing the informed consent at Visit 1 and at Visit 2.
Female patients: (a) All FOCBP must have a negative serum pregnancy test result at the Screening Visit (Visit 1) and a negative urine pregnancy test on the day of randomisation (prior to randomisation; Visit 2) and must not be lactating. (b) Females of non-childbearing potential who are < 55 years old must fulfil one of the following criteria at the Screening Visit: (i) Post-menopausal, defined as amenorrhoea for 12 months following cessation of all exogenous hormonal treatments and FSH levels in the post-menopausal range (historical data for FSH will be accepted). (ii) Permanent sterilisation includes hysterectomy, bilateral oophorectomy, and bilateral salpingectomy at least 6 weeks before screening and is confirmed by the medical records or follow-up hormone level assessment. Bilateral tubal ligation is not acceptable. (c) For females aged 55 years, post-menopausal is defined as having a history of 12 months amenorrhea, without an alternative cause, following cessation of all exogenous hormonal treatments. (d) FOCBP must be willing to use highly effective contraception measures with low user dependency from signing the ICF until 20 days after last dose of study intervention. FOCBP should be stable on their chosen method of birth control for at least 3 months before first dosing.
Male patients: (a) Male patients and their FOCBP partner must be willing to use a highly effective contraception measure and should refrain from donating sperm or fathering a child from the first day of dosing until at least 20 days after last dose of study intervention.
Capable of giving signed informed consent.
Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative.
Documented physician diagnosis of asthma for at least 12 months, as evidenced by any of the following: (a) Post-BD reversibility of FEV1 12% and 200 mL within 5 years prior to Visit 1, or (b) PEF average daily variability > 10% over a 2-week period within 5 years prior to Visit 1, or (c) Variability of FEV1 > 12% and 200 mL between any 2 clinical visits within 5 years prior to Visit 1, or (d) Positive bronchial challenge test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 from pre-challenge of 20% with standard doses of methacholine or 15% with standardised hyperventilation, hypertonic saline, or mannitol challenge, or (e) Positive exercise challenge test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 of > 10% and > 200 mL from pre-challenge, or (f) Significant increase in lung function after 4 weeks of anti-inflammatory treatment with ICS-containing treatment (GINA 2023) within 5 years prior to Visit 1, defined as an increase in FEV1 > 12% and 200 mL (or PEF by >20%)
Treated with medium- or high-dose ICS (as per GINA 2023) in combination with LABA (GINA Step 4 or 5 therapy); the dose of ICS must be stable for at least 30 days prior to Visit 1. The ICS can be contained within an ICS-LABA fixed-dose combination product. Note: Treatment with additional asthma controller therapies (eg, LAMA) at a stable dose 30 days prior to Visit 1 is allowed.
Demonstration of uncontrolled asthma through ACQ-6 score 1.5 at both Visit 1 and Visit 2.
Criterios de exclusión: Life-threatening asthma defined as a history of significant asthma episode(s) involving intubation, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s).
Patients with recent myocardial infarction, unstable angina pectoris, stroke, or percutaneous coronary intervention within 3 months of Visit 1 or coronary artery bypass grafting within 6 months of Visit 1.
A helminth parasitic infection diagnosed within 24 weeks of Visit 1 that has not been treated, or has not responded to SoC therapy.
Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and other recreational drugs including marijuana).
Known history of drug or alcohol abuse within the 12 months prior to Visit 1, that in the Investigators opinion would preclude participation in the study. The use of oral cannabis is permitted.
Current diagnosis of cancer or unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin and cervical carcinoma-in-situ that have been treated and considered cured at the time of enrolment are not exclusionary.
Any other clinically relevant abnormal findings on vital signs, physical examination, or clinical laboratory testing including haematology, coagulation, clinical chemistry, or ECG between Visit 1 and Visit 2, that in the opinion of the Investigator or medical monitor might compromise the safety of the patient in the study or interfere with evaluation of the study intervention. Abnormal findings include, but are not limited to: (a) ALT or AST > 2 × ULN (b) TBL > 1.5 × ULN (unless due to Gilberts disease) Treatment with any of the following therapeutic interventions within the specified time before Visit1
Treatment with marketed or investigational biologics for asthma or immunological disease within 4 months or a minimum of 5 half-lives, prior to Visit 1, whichever is longer.
Systemic steroids within 4 weeks prior to Visit 1.
Chronic oral or systemic CS use for asthma or for any other indication (with the exception of stable replacement therapy in adrenal insufficiency).
Completed treatment for respiratory infection and/or asthma exacerbation with systemic corticosteroids and/or antibiotics for > 3 days in the 4 weeks prior to Visit 1.
Clinically important pulmonary disease other than asthma; including but not limited to those with co-existent chronic obstructive pulmonary disease.
Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the patient throughout the study (b) Influence the findings of the study or their interpretation (c) Impede the patients ability to complete the entire duration of study
Patients who, in the opinion of the Investigator, have evidence of active TB or are currently on treatment for active or latent TB. Investigation for active or latent TB, with interferon gamma release assay (IGRA) and/or chest X-ray, should only be considered if deemed clinically indicated by the Principal Investigator.
Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C, as defined by: (a) Positive test for HBsAg (b) Positive test for anti-HBc: Patients who test positive for anti-HBc antibody but negative for HBsAg may be enrolled if their hepatitis B virus DNA test result is negative (c) Positive test for anti-hepatitis C antibody: Patients who test positive for antihepatitis C antibody may be enrolled if their hepatitis C viral RNA test result is negative in the absence of liver cirrhosis
Patients with history of HIV infection or who test positive for HIV.
Congenital long QT syndrome or prolonged QTcF > 470 ms or history of QT prolongation associated with other medications that required discontinuation of that medication.
Current untreated or uncontrolled arrhythmia (eg, multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia). Note: Patients with clinically significant sinus nodal disease/bradycardia or type 2 second- or third-degree atrioventricular block can be included if treated with a pacemaker.
Centro: Vithas Xanit Internacional
Título: Estudio cruzado, doble ciego, multicéntrico, aleatorizado, de tres periodos y de tres tratamientos para evaluar el efecto de BGF MDI, BFF MDI y placebo de MDI sobre los parámetros del ejercicio en participantes con enfermedad pulmonar obstructiva crónica (ATHLOS)
Especialidad: Neumología
Código de protocolo: D5988C0001
Número EudraCT: 2022-502274-16-00
Promotor: AstraZeneca AB
Investigador principal: Dr. Gustavo de Luiz
Más información:
CRO: Parexel
Centro: Vithas Xanit Internacional
Título: Estudio de investigación para observar cómo funciona ziltivekimab en comparación con placebo en personas con insuficiencia cardíaca e inflamación
Especialidad: Endocrinología
Código de protocolo: EX6018-4915
Número EudraCT: 2022-501939-16-00
Promotor: NovoNordisk
Investigador principal: Dr. Cristóbal Morales Portillo
Más información:
CRO: ICON
Criterios de inclusión: Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
Serum hs-CRP 2 mg/L at screening.
At least one of the following: NT-proBNP 300 pg/mL at screening for patients without ongoing atrial fibrillation/flutter (if ongoing atrial fibrillation/flutter at screening, NTproBNP must be 600 pg/mL).Note that the screening ECG must be obtained the same day as sampling for NT-proBNP. Or HF hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening in combination with NT-proBNP 200 pg/mL at screening for patients without ongoing atrial fibrillation/flutter (if ongoing atrial fibrillation/flutter at screening, NTproBNP must be 600 pg/mL).
Diagnosis of heart failure (NYHA Class II-IV)
LVEF > 40% documented by echocardiography within 12 months prior to or at screening. The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., MI or HF hospitalisation).
Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening showing at least one of the following: LA volume index > 34 mL/m^2, LA diameter 3.8 cm, LA length 5.0 cm, LA area 20 cm^2, LA volume 55 mL, Intraventricular septal thickness 1.1 cm, Posterior wall thickness 1.1 cm, LV mass index 115 gm^2 in men or 95 gm^2 in women, E/e (mean septal and lateral) 10, e (mean septal and lateral) < 9 cm/s.
No heart failure hospitalisations or urgent heart failure visits between screening and randomisation.
Age 18 years or above at the time of signing the informed consent.
Criterios de exclusión: Known or suspected hypersensitivity to study intervention or related products.
Platelet count <120×10^9/L at screening.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × upper limit of normal at screening.
Active hepatitis C (positive anti-HCV and detectable HCV RNA) or hepatitis B (positive HBsAg and/or positive anti-HBc with detectable HBV DNA) at screening. (Note: Participants with positive anti-HBc and undetectable HBV DNA can be enrolled).
Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation within 30 days prior to screening.
Systolic blood pressure 180 mmHg at screening. If the systolic blood pressure is 160-179 mmHg, the patient should be receiving 3 antihypertensive drugs. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
Heart rate above 110 or below 40 beats per minute as evaluated on the ECG performed at screening. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
Planned coronary, carotid or peripheral artery revascularisation known during the screening period. (Note: planned coronary angiogram is not exclusionary).
Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period.
Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation or any major surgical procedure planned at the time of randomisation.
Left Ventricular Assist Device (LVAD) implantation or heart transplantation
Previous randomisation in this study.
Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease.
Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).
Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
History of recurrent serious infections (infections leading to hospitalisation or use of i.v. antibiotics) in the 12 months prior to randomisation, at the discretion of the investigator.
Diagnosis of human immunodeficiency virus (HIV) and not receiving a stable antiretroviral regimen, at the discretion of the investigator at screening.
History or evidence of untreated latent tuberculosis (TB) such as (but not limited to): History of a positive TB test or chest X-ray compatible with latent TB; and TB treatment initiated less than 28 days prior to randomisation.Confirmed positive for latent TB at screening and TB treatment initiated less than 28 days prior to randomisation.
eGFR<15 mL/min/1.73 m^2 (CKD-EPI9) at screening or chronic haemodialysis or peritoneal dialysis.
History of gastrointestinal perforation. (Note: History of perforated appendicitis more than 5 years prior to screening is not exclusionary).
History of active diverticulitis in the 5 years prior to randomisation.
Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
History of inflammatory bowel disease that has been clinically active during the 12 months prior to randomisation.
Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low risk prostate cancer, or in-situ carcinomas of the cervix, or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN)) within 5 years prior to screening.
History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the study. Note: Patients no longer receiving immune suppressant therapy and who are in full remission following bone marrow transplant can be included in the study.
Received a live or attenuated-live vaccine product within 4 weeks of study intervention administration or expected to receive a live or attenuated-live vaccine product during the treatment period. (Note: Not-live and not attenuated-live vaccines are not exclusionary.
Use of preventive systemic antibiotics, systemic antivirals, or systemic antifungals at screening. (Note: Systemic is defined as oral or i.v. administered drugs that are absorbed into the circulation. Antibiotics used to treat latent TB are exempted).
Use of systemic immunosuppressive drugs (both small molecules and biologics) or disease modifying anti-rheumatic drugs (DMARDs including both biologic DMARDs like anti-TNF-alpha and conventional DMARDs like methotrexate) at screening or anticipated chronic use of such drugs any time during the study. (Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary).
Use of anti-IL-6 products at screening or anticipated use of such drugs any time during the study.
Participation (i.e., signed informed consent) in any other interventional clinical study of an approved or non-approved investigational medicinal product within 30 days prior to screening.
Participation in any clinical study of an approved or non-approved device for the treatment of heart failure within 30 days prior to screening.
Any disorder or circumstance, which in the investigators opinion might jeopardise participants safety or compliance with the protocol.
Inadequate standard of care treatment which in the investigators opinion makes participation in the study inappropriate.
Unstable medical therapy for heart failure (including dose of diuretics) within 14 days prior to screening visit (at the discretion of the investigator).
Absolute neutrophil count <2×10^9/L at screening.
Centro: Vithas Sevilla
Título: Estudio fase IIb, aleatorizado, doble ciego, controlado con placebo y con comparador activo abierto para evaluar la eficacia, seguridad y tolerabilidad de AZD5004 en adultos con diabetes mellitus tipo 2
Especialidad: Endocrinología
Código de protocolo: D7261C00001
Número EudraCT: 2024-512562-34-00
Promotor: AstraZeneca
Investigador principal: Dr. Cristóbal Morales Portillo
Más información:
CRO: ICON
Criterios de inclusión: Adults 18 years of age
Diagnosed with T2DM for at least 6 months
HbA1c 7 .0% and 10.5% managed with diet and exercise alone or with a stable dose of metformin or an SGLT2 inhibitor for at least one month prior to screening
Body mass index of 23 kg/m2
Stable self-reported body weight for 3 months prior to randomization ( 5% body weight change)
Capable of giving signed informed consent and complying with study requirements and restrictions listed in the ICF and protocol.
Criterios de exclusión: Type 1 diabetes mellitus, secondary forms of diabetes or history of ketoacidosis or hyperosmolar coma.
History of proliferative diabetic retinopathy, diabetic maculopathy, or severe non-proliferative diabetic retinopathy that required immediate treatment.
Have had more than one episode of severe hypoglycemia within 6 months prior to screening, or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms. Received medication for weight loss within the last 3 months prior to screening.
Clinically significant inflammatory bowel disease, gastroparesis, severe disease or surgery affecting the upper GI tract.
History of acute or chronic pancreatitis.
Cardiac arrhythmias or ECG morphology abnormalities, as considered by the investigator, that may interfere with interpretation of the QT interval corrected for heart rate (QTc) interval changes, including ST wave morphology.
Centro: Vithas Sevilla
Título: Eficacia y seguridad de la coadministración de cagrilintida y semaglutida (CagriSema) una vez por semana versus placebo en participantes con diabetes tipo 2 y neuropatía periférica diabética dolorosa
Especialidad: Endocrinología
Código de protocolo: NN9388-7864
Número EudraCT: 2023-509662-38
Promotor: NovoNordisk
Investigador principal: Dr. Cristóbal Morales Portillo
Más información:
Criterios de inclusión: Male or female.
Age 18years or above at the time of signing the informed consent.
Body mass index (BMI) 25.0kg/m2 at screening.
Diagnosis of type 2 diabetes (T2D) 180days before screening. Stable daily and/or weekly dose(s) 90days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose, as judged by the investigator: Treatment with 1-3 marketed oral antidiabetic drugs (OADs) (metformin, glucosidase inhibitors (AGI), glinides, sodiumglucose cotransporter 2 inhibitors (SGLT2i), DPP4inhibitors, thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local guidelines. Treatment with basal insulin (including NPH (neutral protamine Hagedorn) insulin) according to local guidelines.
HbA1c 10.5% (91mmol/mol) and 6.5% (48 mmol/mol), as determined by central laboratory at screening.
Diagnosis of painful diabetic peripheral neuropathy (pDPN) based on the following criteria: Participant with self-reported pain consistent with pDPN for a minimum of 3 months before screening, as judged by the investigator. AND Michigan Neuropathy Screening Instrument (MNSI) q4 or e2.5 at screening. AND Douleur Neuropathique en 4 Questions (DN4) (Question 1 and 2) 4 at screening.
The weekly average in Pain Intensity-Numerical Rating Scale (PI-NRS) score must meet the following criteria in both weeks during the screening period (day -15 to -8 and day -7 to -1): Completion of daily PI-NRS reporting in the eDiary for a minimum of 4 out of 7 days each week. AND The weekly average PI-NRS score must be 4.0. AND The standard deviation (SD) of the weekly average PI-NRS score must be 2.0.
Stable pharmacological and non-pharmacological treatment of pain for a minimum of 3 months before screening, in the opinion of the investigator. The treatment regimen should adhere to local guidelines (if available).
Criterios de exclusión: Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
Any other painful medical condition(s) where the pain is significantly more severe than the diabetic peripheral neuropathy pain, as judged by the investigator (participants will not be excluded if the pain is transient in nature).
History of suicidal attempt within 5years before screening.
Suicidal behaviour within 1month before screening.
Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30ml/min/1.73m2 as determined by central laboratory at screening.
Exposure to an investigational medicinal product within 90 days or 5half-lives of the investigational medicinal product (if known), whichever is longer, before screening.
Use of any glucagon-like peptide-1 receptor agonist (GLP1 RA), including medication with GLP1 RA activity, or amylin analogue within 60days before screening.
Significant use of opioids, cannabinoids or benzodiazepines within 30days before screening, in the opinion of the investigator.
Anticipated initiation or clinically relevant change in concomitant medications (for more than 14consecutive days during the study) known to affect weight or glucose metabolism (e.g., orlistat, thyroid hormones or oral systemic corticosteroids).
Planned initiation or change in antidepressant, antipsychotic or antiepileptic medication. If participants are already taking such medication, they should have stable and optimised treatment for at least 8weeks before screening.
Presence or history of epilepsy.
Presence or history of fibromyalgia.
Presence of non-diabetic neuropathies, in the opinion of the investigator.
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination and OCT assessment performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
Centro: Vithas Sevilla
