E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Comatose patients with traumatic brain injury (TBI). |
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MedDRA Classification |
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 |
The primary objective of this "first-in-patient" study is to investigate the pharmacokinetics (PK) and efficacy of 2 dose levels of KN 38 7271 after 24-hours IV infusion with KN 38 7271 (1 hour accelerated infusion followed by a 23 hour constant rate infusion with a total dose of 1000 µg or 500 µg KN 38-7271) versus placebo given within 4.5 hours of traumatic brain injury (TBI). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to investigate the efficacy and safety of 2 dose levels of KN 38 7271 after a 24-hour IV infusion with KN 38 7271 (1 hour accelerated infusion followed by a 23 hour constant rate infusion with a total dose of 1000 µg or 500 µg KN 38-7271) versus placebo given within 4.5 hours of TBI on clinical outcome and survival. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18-65 years; 2. Comatose patients with severe TBI and a Glasgow Coma Score (GCS) 3-8 as initially assessed (eg by the emergency physician) after resuscitation and hemodynamical stabilization but before intubation and/or sedation; On arrival at the hospital the study physician should use his own judgement based on the report of the emergency doctor and the current status of the patient that the coma is due to trauma. Patients who have a GCS >8 and/or are not comatose at the scene where the trauma occurred but deteriorate eg, during transport to the hospital may still be eligible for the study; 3. Blunt severe head trauma; 4. Hemodynamically stable (systolic blood pressure > 90 mmHg) after resuscitation/stabilization; 5. Start of treatment with study medication is feasible within 4.5 hours of onset of TBI (where onset of TBI is the time of impact. If the exact time of impact is not known, a conservative approach will be followed for the estimation of time of impact, ie, if an interval was provided for time of impact—eg, between 10:00 and 11:00 hours—the earlier end of that interval [10:00 hours] should be assumed as time of impact; 6. Informed consent obtained according to national and local legislation; 7. Negative urine pregnancy test in all female patients (as all patients are comatose and child bearing potential may not be ruled out in some women.) |
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E.4 | Principal exclusion criteria |
1. TBI due to penetrating head injuries or gun shot wounds; 2. Any major spinal cord injury; 3. Initially bilateral non-reactive dilated pupils; 4. Major injury that requires/is expected to require >2500 mL of blood (> 5 blood units) within 12 hours of TBI; Note: Patients requiring decompressive surgery may still be eligible for this study; 5. Known or CT scan evidence of previous major cerebral damage; 6. Coma due to other causes than TBI; 7. Receiving an experimental drug within 4 weeks prior to current injury; 8. Known history of disability that may interfere with further evaluation; 9. Any severe concomitant disease that may either relevantly affect the safety of the patient, the efficacy of the drug (eg, psychiatric disorders such as, but not limited to, dementia, schizophrenia, mania, personality disorders), or the metabolism of the drug (eg, severe renal or hepatic disease); 10. Patient with known hypersensitivity to any cannabinoids (CB); 11. Patients unlikely to be available for follow-up (eg, patients from abroad); 12. Patients unlikely to survive as determined by qualified study physicians before randomization; 13. Patients with known CB intake within 3 days prior to TBI. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints:
- PK of KN 38 7271 (area under the curve [AUC], maximum concentration [Cmax] after study drug administration (see Table 1) up to 48 jours after start of study medication. - Glasgow Outcome Scale (Extended) (GOSe) - Intracranial pressuere (ICP) - Time to achieve a GCS motor score of 6 - Cerebral lesion change in magnetic resonance imaging (MRI)
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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.8.3 |
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 | 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 | 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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |