Allopregnanolone for the Treatment of Traumatic Brain Injury

NCT ID: NCT01673828

Last Updated: 2017-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2016-07-31

Brief Summary

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.

Detailed 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.

Conditions

Traumatic Brain Injury; Posttraumatic Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Allopregnanolone

Allopregnanolone injection (intravenous solution) continuous infusion for 5 days

Group Type: EXPERIMENTAL

Allopregnanolone injection

Intervention Type: DRUG

Allopregnanolone intravenous solution in 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium

Placebo

Placebo injection (intravenous solution) continuous infusion for 5 days

Group Type: PLACEBO_COMPARATOR

Placebo injection

Intervention Type: DRUG

Placebo intravenous solution, 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium

Interventions

Allopregnanolone injection

Allopregnanolone intravenous solution in 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium

Intervention Type: DRUG

Placebo injection

Placebo intravenous solution, 0.9% sodium chloride injection with 6% sulfobutyl ether β-cyclodextrin sodium

Intervention Type: DRUG

Other Intervention Names

3α,5α-tetrahydroprogesterone; 3α-hydroxy-5α-pregnan-20-one; Product L (allopregnanolone intravenous solution, low dose); Product H (allopregnanolone intravenous solution, high dose); Product P (placebo)

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Michael A. Rogawski, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Michael A. Rogawski, MD, PhD

Principal Invstigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael A Rogawski, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

JoAnne E Natale, MD, PhD

Role: STUDY_DIRECTOR

University of California, Davis

Locations

University of California, Davis Medical Center

Sacramento, California, United States

Countries

United States

Other Identifiers

DR081314

Identifier Type: OTHER

Identifier Source: secondary_id

273147

Identifier Type: -

Identifier Source: org_study_id