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

Primary Purpose

Traumatic Brain Injury

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
JNJ-17299425
Sponsored by
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Traumatic brain injury, JNJ-17299425, Intracranial pressure, Intravascular bolus injection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1: JNJ-17299425

Part 2: JNJ-17299425

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

JNJ-17299425 Plasma Concentration
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])
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])
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
Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
Volume of Distribution (V[d])
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])
Lambda(z) determined by linear regression of the terminal points of the log-linear plasma concentration-time curve
Terminal Half-Life (t[1/2])
Terminal half-life (t[(1/2]) is defined as 0.693/Lambda(z).

Full Information

First Posted
March 18, 2013
Last Updated
April 30, 2013
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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1. Study Identification

Unique Protocol Identification Number
NCT01814982
Brief Title
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

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Why Stopped
reprioritization of company activities
Study Start Date
August 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
Traumatic brain injury, JNJ-17299425, Intracranial pressure, Intravascular bolus injection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: JNJ-17299425
Arm Type
Experimental
Arm Description
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).
Arm Title
Part 2: JNJ-17299425
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
JNJ-17299425
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage Reduction in Intracranial Pressure (ICP)
Description
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
Title
Absolute Intracranial Pressure (ICP) Reduction
Description
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
Title
Duration To Achieve ICP Reduction
Description
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 Outcome Measure Information:
Title
JNJ-17299425 Plasma Concentration
Description
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
Title
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post Dose (AUC [0-24])
Description
The AUC (0-24) is the area under the plasma concentration-time curve from 0 to 24 hours post dosing.
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
Title
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])
Description
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.
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
Title
Clearance
Description
Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
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
Title
Volume of Distribution (V[d])
Description
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.
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
Title
Elimination Rate Constant (Lambda[z])
Description
Lambda(z) determined by linear regression of the terminal points of the log-linear plasma concentration-time curve
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
Title
Terminal Half-Life (t[1/2])
Description
Terminal half-life (t[(1/2]) is defined as 0.693/Lambda(z).
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
Facility Information:
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

12. IPD Sharing Statement

Learn more about this trial

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

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