Clinical trial NCT01814982: An Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of JNJ-17299425 in Participants With Traumatic Brain Injury
Official title: An Open-Label, Single and Repeat Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-17299425 in Patients With Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Traumatic Brain Injury
Keywords: Traumatic brain injury
JNJ-17299425
Intracranial pressure
Intravascular bolus injection
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2013-03-20
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage Reduction in Intracranial Pressure (ICP)
timeFrame: 30 minutes post administration of JNJ-17299425
measure: Absolute Intracranial Pressure (ICP) Reduction
timeFrame: 30 minutes post administration of JNJ-17299425
measure: Duration To Achieve ICP Reduction
timeFrame: 30 minutes post administration of JNJ-17299425
Secondary outcomes:
measure: JNJ-17299425 Plasma Concentration
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post Dose (AUC [0-24])
timeFrame: 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
measure: 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])
timeFrame: 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
measure: Clearance
timeFrame: 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
measure: Volume of Distribution (V[d])
timeFrame: 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
measure: Elimination Rate Constant (Lambda[z])
timeFrame: Pre dose and at 2, 5, 10, 30 minutes and at 1, 2, 3, 4, 6, 9, 12, 24, 36, 48 and 72 hours after first dose and at pre dose and post administration of second dose, at 0.5, 1, 2, 3 and 12 hours after second dose of JNJ-17299425
measure: Terminal Half-Life (t[1/2])
timeFrame: 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
Other outcomes:
Locations:
city: Aalst
country: Belgium
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Genk
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Roeselare
country: Belgium
city: Turnhout
country: Belgium
city: Marseille
country: France
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial
role: STUDY_DIRECTOR
References: