E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Traumatic Brain Injury (TBI) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060690 |
E.1.2 | Term | Traumatic brain injury |
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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 determine whether JNJ-17299425 can reduce the increased intracranial pressure (ICP) after traumatic brain injury. The primary pharmacodynamic (PD) parameter is the reduction of ICP; the percentage reduction will be characterized, as well as the absolute reduction, and the reduction below 20 mmHg. The duration of the ICP reduction will also be analyzed. Additionally, the safety, tolerability and maximum safe dose of JNJ-17299425. |
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E.2.2 | Secondary objectives of the trial |
To determine the effects of JNJ-17299425 on cerebral perfusion pressure (CPP), mean arterial blood pressure (MABP), and clinical scoring assessment. To investigate the pharmacokinetic (PK) profile of JNJ-17299425. To investigate a PK/PD relationship of JNJ-17299425. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with traumatic head injury and requiring intra-cranial pressure monitoring. Male or female between 18 and 65 years of age, inclusive. Female subjects: post menopausal as defined by FSH and LH, or previously documented sterilization. Body Mass Index (BMI): 18 to 35 kg/m2 inclusive (BMI = weight/height2). Legally acceptable representatives (relatives/guardians) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are allowing the subject to participate in the study. Moderately increased ICP (ICP>20 mmHG and CPP greater than or equal to 60mmHg) after initial response (to <20mmHg), to a maximum of 3 ventricular drainages. Hb greater than or equal to 8 g/dL. Thrombocytes count greater than or equal to 100.000/microLiters. Potassium less than or equal to 5mmol/L. |
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E.4 | Principal exclusion criteria |
Major injury (multitrauma) or disease outside the CNS causing significant vital organ- or blood counts dysfunction (eg Disseminated Intravascular Coagulation (DIC), serious hepatic or kidney failure, (Acute Respiratory Distress Syndrome (ARDS) etc.). Subjects who already received specific ICP lowering therapy, other than ventricular drainage, before being dosed with JNJ-17299425. Rapid increase of ICP expected to result in death of the subject. Relevant abnormal values for hematology, clinical chemistry or urinalysis at admission. In particular, a clinically significant abnormal hematology profile, or unacceptable bleeding diathesis. Any known significant history or family history of anemia, hemolytic or otherwise, or autoimmune disease. Significant non-brain trauma. On CT scan, compressive hematoma and more than 2 cm midline shift resulting in need for cranial surgery, or other features that would make the need for surgery likely. Any known significant history or family history of thrombocytopenia (eg idiopathic thrombocytopenia). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacodynamic parameter is the reduction of ICP. Percentage of subjects with an ICP reduction to below 20 mmHg and the duration of the ICP reduction. Safety and tolerabilility and determination of maximum safe dose of JNJ 17299425. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 | 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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 20 |