An Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of JNJ-17299425 in Participants With Traumatic Brain Injury

NCT01814982 | Terminated Phase 2 DMC

• 3 other identifiers: CR0129972007-000280-1717299425TRM2001
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 11

Brief Summary

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics (explores what the body does to the drug) and pharmacodynamics (the study of the action or effects a drug has on the body) of JNJ-17299425 in participants with traumatic brain injury (acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem).

Conditions

Traumatic Brain Injury

Keywords

Traumatic brain injury; JNJ-17299425; Intracranial pressure; Intravascular bolus injection

Outcome Measures

Primary Outcomes (3)

• Percentage Reduction in Intracranial Pressure (ICP)

  The ICP is defined as the pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, cerebrospinal fluid dynamics, and skull rigidity. Percentage reduction in ICP and reduction in ICP below 20 millimeter of mercury (mmHG) and a reduction of at least 15 percent ICP will be evaluated. Percentage reduction in ICP means ICP value at Baseline minus ICP value post administration of JNJ-17299425, divided by 100.

  30 minutes post administration of JNJ-17299425

• Absolute Intracranial Pressure (ICP) Reduction

  Absolute ICP reduction is defined as difference between pre dose ICP and lowest ICP value achieved where ICP is pressure within cranial cavity.

  30 minutes post administration of JNJ-17299425

• Duration To Achieve ICP Reduction

  Duration to achieve ICP reduction will assess the time at which ICP value is less than 20mmHg, and the time to achieve 50 percent and below 50 percent of absolute ICP reduction, and time at which lowest ICP value is achieved. Percentage reduction in ICP means ICP value at Baseline minus ICP value post administration of JNJ-17299425, divided by 100 and absolute ICP reduction is defined as difference between pre dose ICP and lowest ICP value achieved where ICP is pressure within cranial cavity.

  30 minutes post administration of JNJ-17299425

Secondary Outcomes (7)

• JNJ-17299425 Plasma Concentration

  Pre dose and 2, 5, 10, 30 minutes and 1, 2, 3, 4, 6, 9, 12, 24, 36, 48 and 72 hours post administration of JNJ-17299425

• Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post Dose (AUC [0-24])

  Pre dose and 2, 5, 10, 30 minutes and 1, 2, 3, 4, 6, 9, 12, 24, 36, 48 and 72 hours post administration of first dose of JNJ-17299425, and at pre dose and 0.5, 1, 2, 3 and 12 hours post administration of second dose of JNJ-17299425

• Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Last Quantifiable Concentration (AUC[0-t]) and AUC From Time 0 to Infinite time (AUC ([0-infinity])

  Pre dose and 2, 5, 10, 30 minutes and 1, 2, 3, 4, 6, 9, 12, 24, 36, 48 and 72 hours post administration of first dose of JNJ-17299425, and at pre dose and 0.5, 1, 2, 3 and 12 hours post administration of second dose of JNJ-17299425

• Clearance

  Pre dose and 2, 5, 10, 30 minutes and 1, 2, 3, 4, 6, 9, 12, 24, 36, 48 and 72 hours post administration of first dose of JNJ-17299425, and at pre dose and 0.5, 1, 2, 3 and 12 hours post administration of second dose of JNJ-17299425

• Volume of Distribution (V[d])

  Pre dose and 2, 5, 10, 30 minutes and 1, 2, 3, 4, 6, 9, 12, 24, 36, 48 and 72 hours post administration of first dose of JNJ-17299425, and at pre dose and 0.5, 1, 2, 3 and 12 hours post administration of second dose of JNJ-17299425

Study Arms (2)

Part 1: JNJ-17299425

EXPERIMENTAL

JNJ-1729425 will be administered once as 1 milligram (10 milliliter of a 0.1 milligram/milliliter (mg/ml) solution) intravenous bolus injection over 2 minutes in central vein. In case of no toxicity or Intra cranial pressure response, dose will be increased to a maximum of 200 milligram (mg).

Drug: JNJ-17299425

Part 2: JNJ-17299425

EXPERIMENTAL

JNJ-1729425 will be repeated once at a dose (which is, determined by Investigator in Part 1) as intravenous bolus injection over 2 minutes in central vein.

Drug: JNJ-17299425

Interventions

JNJ-17299425 DRUG

JNJ-17299425 will be administered at a starting dose of 1 milligram (10 milliliter of a 0.1 mg/ml solution) as intravenous bolus injection over 2 minutes in central vein.

Part 1: JNJ-17299425; Part 2: JNJ-17299425

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with traumatic head injury and requiring intracranial pressure (ICP) monitoring
• Post menopausal females, (or when known not to have menstruated for at least 12 months), or previously documented sterilization
• Body Mass Index (BMI=weight per square height): 18 to 35 kilogram per square meter inclusive
• Legally acceptable representatives (relatives or 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 participant to participate in the study
• To participate in the optional pharmacogenomic component of this study, legally acceptable representatives (relatives or guardians) must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to consent for this component does not exclude a participant from participation in the clinical study

You may not qualify if:

• Major injury (multi-trauma) or disease outside the central nervous system causing significant vital organ or blood counts dysfunction (for example, disseminated intravascular coagulation, serious hepatic or kidney failure, acute respiratory distress syndrome, etc)
• Participants 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 participant
• Relevant abnormal values for hematology, clinical chemistry or urinalysis at admission
• Any known significant history or family history of anemia, hemolytic or autoimmune disease or thrombocytopenia

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead

Study Sites (11)

Unknown Facility

Aalst, Belgium

Location

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Edegem, Belgium

Location

Unknown Facility

Genk, Belgium

Location

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Kortrijk, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Liège, Belgium

Location

Unknown Facility

Roeselare, Belgium

Location

Unknown Facility

Turnhout, Belgium

Location

Unknown Facility

Marseille, France

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial

  Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2013
• First Posted: March 20, 2013
• Study Start: August 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: May 1, 2013

Record last verified: 2013-04

Locations

FR (1); BE (10)