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

Phase 2TerminatedNCT01814982

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.7 enrolled

Overview

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).

This is an open-label (all people know the identity of the intervention), multi-center (conducted in more than one center), and exploratory study of single and repeat, escalating, intravenous (injection of a substance into a vein) doses of JNJ-17299425 in participants with traumatic brain injury. The study consists of 2 parts (Part 1 and Part 2), and each part will have 2 stages (Stage 1 and Stage 2). In Stage 1 of each part only standard care will be given, through sedation, analgesia and ventilation. If Intra cranial pressure (ICP) rises to greater than 20 millimeter of mercury (mmHG) after ventricular drainage, participants will enter Stage 2 of each part and will receive JNJ-17299425 (single dose in Part 1 and repeated dose in Part 2). During Part 1, safety and efficacy of JNJ-17299425 will be evaluated and during Part 2, safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses will be evaluated. Efficacy will primarily be evaluated by reduction in ICP. Blood samples will be collected for pharmacokinetic evaluation at pre and post administration of study treatment. Participants' safety will be monitored throughout the study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Traumatic Brain Injury

Interventions

JNJ-17299425DRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (11)

Unnamed facility

Aalst, Belgium

Unnamed facility

Brussels, Belgium

Unnamed facility

Edegem, Belgium

Unnamed facility

Genk, Belgium

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 30 minutes post administration of JNJ-17299425

Secondary Outcomes

JNJ-17299425 Plasma Concentration

Plasma concentration of JNJ-17299425 will be determined by collecting venous blood samples at the defined time points.

Time frame: 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])

Data from ClinicalTrials.gov

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