E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Central nervous system (CNS) pathology |
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E.1.1.1 | Medical condition in easily understood language |
Brain and spinal cord conditions |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029820 |
E.1.2 | Term | Nuclear magnetic resonance imaging gadolinium-enhanced |
E.1.2 | System Organ Class | 100000004848 |
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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 | 10051290 |
E.1.2 | Term | Central nervous system lesion |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
To identify a dose for further development that has an overall diagnostic preference rate similar to that of the comparator gadobutrol at 5 min post injection |
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E.2.2 | Secondary objectives of the trial |
To show non-inferiority of BAY1747846 compared to gadobutrol at 5 min post injection with respect to sum of lesion visualization parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be at least 18 years of age at the time of signing the informed consent. 2. Known or highly suspected CNS pathology (contrast-enhancing CNS lesion) referred for contrast-enhanced MRI of the CNS. 3. Male and female. 4. Estimated glomerular filtration rate (eGFR) value ≥60 mL/min/1.73m2 at baseline. With regards to baseline of period 1, eGFR value can be derived from a serum creatinine result within 4 weeks prior to the first study MRI determined by local hospital lab. |
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E.4 | Principal exclusion criteria |
1. Considered clinically unstable. 2. Severe cardiovascular disease. 3. Patients undergoing liver transplantation. 4. Any contraindication to MRI examinations. 5. History of severe allergic or anaphylactic/anaphylactoid reaction to any allergen including drugs and contrast agents. 6. History of allergic asthma. 7 Suspected lesions or suffering from any of the following CNS diseases/lesion types as the main indication for MRI: • Meningeal disease (focal enhancement) • Pituitary adenomas (macro and micro) • Tumors of the choroid plexus • Tumors of the pineal gland • Dermoid/epidermoid tumors • Infectious disease (e.g. brain abscess, cisticercosis, etc.) • Venous angiomas • Subacute/chronic ischemia • Encephalitis • Multiple sclerosis (acute and chronic) • Optic neuritis • Chordomas • Von Hippel Lindau syndrome • Hypertensive leukoencephalopathy. 8. Receipt of any contrast agent <72 h prior to the study MRIs, or planned receipt of any contrast agent within 72 h after the second study MRI. 9 Planned or expected biopsy or any interventional therapeutic procedure from the first study MRI up to 24 h after the second study MRI. 10. Planned or expected change in any treatment or procedure between the two study MRIs that may alter image comparability and /or chemotherapy which is changed between the two MRI procedures. 11. Has been previously enrolled in this study. 12. Has received any investigational product within 30 days, or within 5 times half-life of the investigational product, whichever is shorter, prior to enrolling in this study. Note: Participants who have entered the follow-up period of or have been discontinued from an investigational study may participate as long as it has been 30 days after the last dose of the previous investigational product, or 5 times half-life of that investigational product, whichever is shorter. 13. Contraindications to the administration of gadobutrol (depending on local product label).
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall diagnostic preference |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 5 minute post injection |
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E.5.2 | Secondary end point(s) |
Sum of lesion visualization parameters - Lesion visualization parameters (border delineation, contrast enhancement, internal morphology) on pre-contrast and combined pre- and post-contrast (5 min pi) images; - Number of lesions on pre-contrast and combined pre and post-contrast (5 min pi) images |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 5 minute post injection |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 |
Japan |
United States |
Bulgaria |
Germany |
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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
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |