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

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ClinicalTrials.gov Identifier: NCT01814982
Recruitment Status : Terminated (reprioritization of company activities)
First Posted : March 20, 2013
Last Update Posted : May 1, 2013
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Tracking Information
First Submitted Date  ICMJE March 18, 2013
First Posted Date  ICMJE March 20, 2013
Last Update Posted Date May 1, 2013
Study Start Date  ICMJE August 2007
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2013)
  • Percentage Reduction in Intracranial Pressure (ICP) [ Time Frame: 30 minutes post administration of JNJ-17299425 ]
    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.
  • Absolute Intracranial Pressure (ICP) Reduction [ Time Frame: 30 minutes post administration of JNJ-17299425 ]
    Absolute ICP reduction is defined as difference between pre dose ICP and lowest ICP value achieved where ICP is pressure within cranial cavity.
  • Duration To Achieve ICP Reduction [ Time Frame: 30 minutes post administration of JNJ-17299425 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2013)
  • Percentage Reduction in Intracranial Pressure (ICP) [ Time Frame: 30 minutes post administration of JNJ-17299425 ]
    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.
  • Absolute Intracranial Pressure (ICP) Reduction [ Time Frame: 30 minutes post administration of JNJ-17299425 ]
    Absolute ICP reduction is defined as difference between pre dose ICP and lowest ICP value achieved where ICP is pressure within cranial cavity.
  • Duration To Achieve ICP Reduction [ Time Frame: 30 minutes post administration of JNJ-17299425 ]
    Duration to acheive ICP reduction will assess the time at which ICP value is less than 20mmHg, and the time to acheive 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.
Change History Complete list of historical versions of study NCT01814982 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2013)
  • JNJ-17299425 Plasma Concentration [ 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 ]
    Plasma concentration of JNJ-17299425 will be determined by collecting venous blood samples at the defined time points.
  • Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post Dose (AUC [0-24]) [ 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 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 ]
    The AUC (0-24) is the area under the plasma concentration-time curve from 0 to 24 hours post dosing.
  • 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]) [ 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 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 ]
    The AUC (0-infinity) calculated by trapezoidal summation (time t is the time of the last quantifiable concentration C[last]) and AUC (infinity) is the area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUC(last) and C(last)/l(z), in which C(last) is the last observed quantifiable concentration.
  • Clearance [ 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 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 is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Volume of Distribution (V[d]) [ 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 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 is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
  • Elimination Rate Constant (Lambda[z]) [ Time Frame: 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 ]
    Lambda(z) determined by linear regression of the terminal points of the log-linear plasma concentration-time curve
  • Terminal Half-Life (t[1/2]) [ 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 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 ]
    Terminal half-life (t[(1/2]) is defined as 0.693/Lambda(z).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of JNJ-17299425 in Participants With Traumatic Brain Injury
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Traumatic Brain Injury
Intervention  ICMJE Drug: JNJ-17299425
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.
Study Arms  ICMJE
  • Experimental: Part 1: JNJ-17299425
    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).
    Intervention: Drug: JNJ-17299425
  • Experimental: Part 2: JNJ-17299425
    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.
    Intervention: Drug: JNJ-17299425
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 18, 2013)
7
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2008
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01814982
Other Study ID Numbers  ICMJE CR012997
2007-000280-17 ( EudraCT Number )
17299425TRM2001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study Sponsor  ICMJE Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
PRS Account Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP