Allopregnanolone for the Treatment of Traumatic Brain Injury

Michael A. Rogawski, MD, PhD

Status and phase

Completed

Phase 2

Conditions

Traumatic Brain Injury

Posttraumatic Epilepsy

Treatments

Drug: Placebo injection

Drug: Allopregnanolone injection

Study type

Interventional

Funder types

Other

Other U.S. Federal agency

Identifiers

NCT01673828

273147

DR081314 (Other Identifier)

Details and patient eligibility

About

This study will provide initial data on the safety and effectiveness of allopregnanolone in improving neurobehavioral outcome and reducing mortality in adults with moderate and severe traumatic brain injury.

Full description

This is a double-blind, placebo-controlled, randomized, dose-finding, two-stage adaptive, clinical trial study comparing allopregnanolone to placebo when administered intravenously for 5 days beginning within 8 hours after injury. Test products to be administered are low and high dose allopregnanolone (Products L and H, respectively) and placebo (Product P) intravenous solutions. The products are administered during a 4-day treatment period followed by a 1-day dose de-escalation period. Stage 1 of the study will assess safety and confirm that dosing with Products L and H achieve the target steady-state plasma concentrations set for each of these products. Dosing will be adjusted in Stage 1, if necessary. Stage 2 will initially allocate subjects equally to Products L, H and P but will then use adaptive randomization to allocate subjects between Products L and H to optimized the probability of yielding a better 3-month Glasgow Outcome Score Extended (GOS-E) score.

Enrollment

13 patients

Sex

All

Ages

16 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

English or Spanish speaking person
Moderate to severe closed or blunt traumatic brain injury [post resuscitation Glasgow Coma Score (GCS) 3-12 with abnormal head CT scan if GCS is 9-12]
Less than 8 hours from injury to study initiation
Able to participate for the full term of the study

Exclusion criteria

Subjects with life expectancy of less than 24 hours
Isolated epidural hematoma
Hypoxia (pulse oximetry saturation ≤90% for 15 or more minutes before enrollment)
Hypotension (systolic blood pressure ≤90 mm Hg on 2 or more reliable measurements before enrollment)
Cardiopulmonary arrest prior to randomization
Spinal cord injury with motor deficits
Bilateral non-reactive pupils with Glasgow Coma Scale 3
Body weight >120 kg
Pregnancy
Active breast or reproductive organ cancer
Allergy to progesterone
History of thromboembolic events
Receipt of activated Factor VII before enrollment
Any disease that is unstable or which could jeopardize the safety of the subject including severe renal impairment (creatinine clearance <50 ml/min)
Prisoner/ward of the state
Known treatment with another investigational drug therapy or procedure within 30 days of injury