Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury

Inclusion Criteria:

1. Male or female patients between the age of 16 and 70 years, inclusive

2. Weight from 45 to 135 kg, inclusive

3. Sustained a closed head trauma no more than 8 hours before start of study drug
infusion

4. TBI diagnosed by history and clinical examination

5. Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive

6. At least one reactive pupil (pinpoint pupils due to opioid pain treatment are
considered reactive)

7. Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon
admission (diffuse injury II-IV, evacuated and non-evacuated mass lesion, Marshall's
CT Classification)

8. Indication for ICP monitoring

Exclusion Criteria:

1. Life expectancy of less than 24 hours as determined by the Investigator

2. Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood
pressure < 90 mmHg) at the time of randomization

3. Any spinal cord injury

4. Pregnancy

5. Penetrating head injury

6. Bilaterally fixed dilated pupils at the time of randomization

7. Coma suspected to be primarily due to other causes (e.g. alcohol)

8. Pure epidural hematoma

9. Preexisting clinically significant disease or chronic condition that can be
ascertained at the time of admission and could affect functional outcome

10. Severe cardiac or hemodynamic instability prior to randomization

11. Known treatment with another investigational drug therapy or procedure within 30 days
of injury

12. A history of allergic reaction to progesterone and related drugs or any of the
components of the infusion

13. Any disease, in the opinion of the Investigator, that is unstable or which could
jeopardize the safety of the patient and his/her compliance in the study.

14. Patients who, in the opinion of the Investigator, would not be able or willing to
comply with the protocol through the final visit (6 months post-injury)