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NCT00638989

A Study to Assess Bioavailability and Pharmacokinetics of CAT- 354

Completed Phase 1 Results posted Last updated 4 May 2017
What this trial tests

Phase 1 trial testing CAT-354 150 mg (intravenous) in Asthma in 30 participants. Completed in 7 June 2008.

Timeline
11 April 2008
Primary endpoint
7 June 2008
7 June 2008

Quick facts

Lead sponsorMedImmune LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment30
Start date11 April 2008
Primary completion7 June 2008
Estimated completion7 June 2008
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

MedImmune LLC — full company profile →

Who can join

Adults 19 to 55, male only, with Asthma or Healthy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Absolute Bioavailability of CAT-354 After Subcutaneous Dose Primary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56

Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. Absolute bioavailability of the subcutaneous doses was assessed by the geometric least-square means ratios of subcutaneous to intravenous dose-normalized area under the serum concentration-time curve from time zero to infinity (AUC \[0 - infinity\]/Dose). AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).

GroupValue95% CI
CAT-354 150 mg (Subcutaneous)62.148.5 – 79.6
CAT-354 300 mg (Subcutaneous)60.146.9 – 77.1
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Secondary · Day 0 to 56

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Day 56 that were absent before treatment or that worsened relati

TEAEs
GroupValue95% CI
CAT-354 150 mg (Intravenous)5
CAT-354 150 mg (Subcutaneous)5
CAT-354 300 mg (Subcutaneous)4
TESAEs
GroupValue95% CI
CAT-354 150 mg (Intravenous)0
CAT-354 150 mg (Subcutaneous)0
CAT-354 300 mg (Subcutaneous)0
Number of Participants Exhibiting Anti-Drug Antibodies for CAT-354 at Any Visit Secondary · Day 0 and Day 56
GroupValue95% CI
CAT-354 150 mg (Intravenous)0
CAT-354 150 mg (Subcutaneous)0
CAT-354 300 mg (Subcutaneous)0
Area Under the Concentration-time Curve From Zero to Infinity (AUC [0 - Infinity]) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56

AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity).

GroupValue95% CI
CAT-354 150 mg (Intravenous)903± 291
CAT-354 150 mg (Subcutaneous)548± 143
CAT-354 300 mg (Subcutaneous)1080± 315
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - 56]) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
GroupValue95% CI
CAT-354 150 mg (Intravenous)765± 220
CAT-354 150 mg (Subcutaneous)467± 122
CAT-354 300 mg (Subcutaneous)881± 287
Dose Normalized Area Under the Concentration-time Curve From Zero to Infinity ([AUC {0 - Infinity}]/Dose) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56

AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). (AUC \[0 - infinity\]) was normalized by CAT-354 dose.

GroupValue95% CI
CAT-354 150 mg (Intravenous)6.02± 1.94
CAT-354 150 mg (Subcutaneous)3.66± 0.953
CAT-354 300 mg (Subcutaneous)3.59± 1.05
Maximum Observed Serum Concentration (Cmax) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
GroupValue95% CI
CAT-354 150 mg (Intravenous)58.3± 14.4
CAT-354 150 mg (Subcutaneous)17.1± 5.91
CAT-354 300 mg (Subcutaneous)36.6± 13.1
Dose Normalized Maximum Observed Concentration (Cmax/Dose) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
GroupValue95% CI
CAT-354 150 mg (Intravenous)0.389± 0.096
CAT-354 150 mg (Subcutaneous)0.114± 0.039
CAT-354 300 mg (Subcutaneous)0.122± 0.044
Time to Reach Maximum Observed Serum Concentration (Tmax) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56
GroupValue95% CI
CAT-354 150 mg (Intravenous)0.0630.042 – 1.02
CAT-354 150 mg (Subcutaneous)53 – 9
CAT-354 300 mg (Subcutaneous)53 – 9
Terminal Phase Elimination Half Life (t1/2) Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion/post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56

Terminal phase elimination half-life is the time measured for the serum concentration to decrease by one half.

GroupValue95% CI
CAT-354 150 mg (Intravenous)21.4± 2.46
CAT-354 150 mg (Subcutaneous)19.2± 3.1
CAT-354 300 mg (Subcutaneous)19.4± 3.59
Apparent Systemic Clearance (CL/F) After Subcutaneous Dose Secondary · Predose, 30 minutes, at 1, 3, 8 and 24 hours post-injection on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after subcutaneous dose (apparent systemic clearance) is influenced by the fraction of the dose absorbed (bioavailability).

GroupValue95% CI
CAT-354 150 mg (Subcutaneous)292± 82.3
CAT-354 300 mg (Subcutaneous)307± 109
Apparent Systemic Clearance (CL/F) After Intravenous Dose Secondary · Predose, end of infusion, 30 minutes, 1, 3, 8 and 24 hours post-end of infusion on Day 0; Day 3, 5, 7, 9, 14, 21, 28, 35, 42 and 56

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

GroupValue95% CI
CAT-354 150 mg (Intravenous)188± 84.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 0 to 56. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CAT-354 150 mg (Intravenous)
Serious: 0/10 (0%)
Deaths:
CAT-354 150 mg (Subcutaneous)
Serious: 0/10 (0%)
Deaths:
CAT-354 300 mg (Subcutaneous)
Serious: 0/10 (0%)
Deaths:
Other adverse events (25 terms — click to expand)

ReactionSystemCAT-354 150 mg (Intravenous)CAT-354 150 mg (Subcutaneo…CAT-354 300 mg (Subcutaneo…
HeadacheNervous system disorders
Paranasal sinus hypeRespiratory, thoracic and mediastinal disorders
Eye pruritusEye disorders
Abdominal painGastrointestinal disorders
Feeling coldGeneral disorders
Feeling hotGeneral disorders
Post-traumatic painInjury, poisoning and procedural complications
Procedural painInjury, poisoning and procedural complications
SunburnInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Joint swellingMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Melanocytic naevusNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DizzinessNervous system disorders
Sinus headacheNervous system disorders
SomnolenceNervous system disorders
Breast massReproductive system and breast disorders
Breast tendernessReproductive system and breast disorders
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Pharyngolaryngeal paRespiratory, thoracic and mediastinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Sinus congestionRespiratory, thoracic and mediastinal disorders
SneezingRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT00638989 adverse events section.

Sponsor's own description

To compare bioavailability and pharmacokinetics of CAT-354 following subcutaneous administration compared with intravenous administration.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways.
    Ewald DA, Malajian D, Krueger JG, Workman CT, et al · · 2015 · cited 125× · PMID 26459294 · DOI 10.1186/s12920-015-0133-x
  2. Pharmacokinetics of tralokinumab in adolescents with asthma: implications for future dosing.
    Baverel PG, Jain M, Stelmach I, She D, et al · · 2015 · cited 22× · PMID 26182954 · DOI 10.1111/bcp.12725
  3. Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma.
    Gallagher A, Edwards M, Nair P, Drew S, et al · · 2021 · cited 19× · PMID 34664263 · DOI 10.1002/14651858.cd012929.pub2
  4. Mechanistic modeling of a human IgG<sub>4</sub> monoclonal antibody (tralokinumab) Fab-arm exchange with endogenous IgG<sub>4</sub> in healthy volunteers.
    Wang B, Goodman J, Roskos LK. · · 2022 · cited 2× · PMID 35023315 · DOI 10.1002/psp4.12738

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