None listed
Conditions
Brief summary
This is a phase 1 study in healthy subjects. It is planned to develop the drug for reducing pressure in the brain of patients with a traumatic brain injury (TBI). Increased pressure following TBI can lead to death or can cause permanent disability. There are currently no medications that are approved for improving outcomes after TBI. The drug will also be tested for improving clinical outcome in patients that suffered a concussion. The study drug being evaluated is called EU-C-001 and is being developed by an Australian company called PresSura Neuro. Studies in animals have shown that EU-C-001 may reduce pressure in the brain. Therefore, it is thought that EU-C-001 may improve outcomes in patients with TBI by increasing the amount of oxygen available to brain tissue. In other studies it was shown that the EU-C-001 may also have potential to improve outcomes in patients with concussion. This is the first in-man study planned to assess the pharmacodynamic potency as well as safety and tolerability and pharmacokinetics in man after a single intravenous administration when given together with apomorphine. The ability of EU-C-001 to penetrate the human brain is an important prerequisite for efficacy in its core indications. The inhibition of apomorphine-induced emesis will be used in this study as proof of receptor occupancy and EU-C-001 brain penetrance.
Interventions
Group [1]
(a) Five male subjects will receive one intravenous infusion of 90 mg EU-C-001.
(b) Five male subjects will receive one intravenous infusion of 15 mg EU-C-001.
(c) Five male subjects will receive one intravenous infusion of 5 mg EU-C-001 (To be investigated only if the 90 mg and the 15 mg doses show comparable activity in the apomorphine challenge).
The doses will be administered in descending ordered starting with the 90 mg dose (a) with staggered starts for the cohorts of at least
Group [1] (a) Five male subjects will receive one intravenous infusion of 90 mg EU-C-001. (b) Five male subjects will receive one intravenous infusion of 15 mg EU-C-001. (c) Five male subjects will receive one intravenous infusion of 5 mg EU-C-001 (To be investigated only if the 90 mg and the 15 mg doses show comparable activity in the apomorphine challenge). The doses will be administered in descending ordered starting with the 90 mg dose (a) with staggered starts for the cohorts of at least 24 hours. The lowest dose of 5 mg EU-C-001 will only be investigated if the 90 mg and the 15 mg doses show comparable activity in the apomorphine challenge.. If the 90 mg and the 15 mg doses do not show comparable activity in the apomorphine challenge, Group c will not be administered the study drug.. Subjects will be monitored for clinically relevant gastrointestinal adverse events like e.g., nausea, vomiting, and retches when challenged with apomorphine 2 hours after the start of the EU-C_001 infusion. Apomorphine challenge Two hours (120 minutes) after start of the EU-C-001 infusion, the subjects will receive a subcutaneous injection of 50 µg/kg apomorphine. After EU-C-001 infusion, subjects will be monitored during blood sampling for pharmacokinetecs at 15-20 minute intervals up to 1 hour, and for adverse events at 1.0, 1.5, 2, 2.5, 3.0, 4.0, 6.0, 8.0, 10., 12, and 24 hours. Group [2] Six male subjects (not included in Group 1) will each receive seven 30-minute intravenous infusions of 90 mg EU-C-001 in 12-hour intervals. Administration of study drug to Group 2 will start not less than 24 hours after Group 1 (a). After EU-C-001 infusion, subjects will be monitored during blood sampling for pharmacokinetecs at 15-20 minute intervals up to 4 hours, and for adverse events at 1.0, 2, 4.0, 8.0, and 12 hours. Stopping criteria are occurrence of abnormal results at safety assessments (e.g. laboratory values) and / or systemic adverse events all being of clinical relevance. All doses are administered at a dedicated clinical trial facility under controlled conditions by the investigators. The dose administrations will be made under direct medical supervision. The precise date and time of the administration shall than be documented in the CRF.
Sponsors
PresSura Neuro Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy male subjects, age 18 to 45 years, healthy as defined by medical history, physical and biological examinations performed prior to inclusion. 1. Gender Male 2. Age: Between 18 and 45years 3. Weight: 55.0–95.0 kg 4. BMI: 19.0–29.0 kg/m2 5. Medical history without clinically relevant pathologies 6. Physical examination parameters without signs of clinically relevant pathologies 7. Electrocardiogram recording without signs of clinically relevant pathology, in particular QTc (Bazett) <450 ms 8. Values for hematology and for biochemistry tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the medical investigator (in particular normal values for ALT, AST, Gamma-GT) 9. Having given written informed consent before any study-related activities are carried out 10. Willing and able to use a condom for all sexual intercourse and practice a medically approved method of contraception with female partners (e.g., condom in combination with hormonal contraception or intrauterine device or a diaphragm) throughout the study and for 1 month after the last study drug administration
Exclusion criteria
Subjects will not be eligible for the study, if they fulfill one or more of the following exclusion criteria: 1. Evidence of clinically relevant pathology or disease 2. Evidence of moderate or severe hypertension, hypotension or orthostatic hypotension (fall in systolic blood pressure of >20 mmHg on standing up from supine) 3. Unwilling and/or incapable of giving informed consent 4. Any history of clinically important psychiatric illness eg history of depression treated with antidepressant or of any clinically important neurological or neuro-muscular disorders and/or epilepsy 5. Having had any previous traumatic brain injury, concussion or unexplained loss of consciousness 6. Acute or chronic gastrointestinal disorders 7. Presence or history of endocrine disorders 8. Known hypersensitivity to the study drug or constituent of the study drug 9. History of immediate hypersensitivity to any drug, 10. Strict vegetarian or vegan 11. Regular treatment with medications during three months prior to screening 12. Receipt of any prescription or non-prescription medication, complementary therapies including multi-vitamin preparations within 14 days prior to the day of the first pharmacokinetic assessment and for the duration of the study with the exception of paracetamol at a dose less than or equal to 2g per day 13. Participation in a clinical study within 90 days prior to randomization or within 7 half-lives of a previous investigational agent 14. Having already received EU-C-001 15. Donation of blood within 90 days prior to screening 16. Receipt of blood, blood products or plasma derivatives one year prior to randomization 17. History of use of tobacco or nicotine-containing products within the past three months 18. Any history of alcohol abuse or drug addiction 19. Positive results at screening for drugs of abuse (Methamphetamines / Opiates / Cocaine / Cannabinoids / Phencyclidine / Benzodiazepines / Barbiturates / Methadone / Tricyclic Antidepressants / Amphetamines) or alcohol (breath test) at screening or on admission 20. Positive screen results for HBsAg, anti-HCV, or anti-HIV1&2 (except for subjects vaccinated for hepatitis or subjects with past but resolved hepatitis) 21. Consumption of abnormal quantities of coffee or tea or other caffeinated drinks (i.e., more than 5 cups per day [1 cup = 150 ml]) 22. Any disease which in the Investigator’s opinion would exclude the subject from the study. 23. Any indication of respiratory impairment
Outcome results
None listed