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

April 30, 2013 updated by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium
      • Bruxelles, Belgium
      • Edegem, Belgium
      • Genk, Belgium
      • Gent, Belgium
      • Kortrijk, Belgium
      • Leuven, Belgium
      • Liege, Belgium
      • Roeselare, Belgium
      • Turnhout, Belgium
  • France
      • Marseille, France

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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).
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
30 minutes post administration of JNJ-17299425
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.
30 minutes post administration of JNJ-17299425
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.
30 minutes post administration of JNJ-17299425

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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])
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.
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])
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.
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
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.
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])
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.
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
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
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
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).
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 18, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 1, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR012997
  • 2007-000280-17 (EudraCT Number)
  • 17299425TRM2001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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