A Study of Tralokinumab When Delivered Subcutaneously at Different Flow Rates to Healthy Volunteers

A Phase 1 Study to Evaluate the Pharmacokinetics and Tolerability of a Single Subcutaneous Dose of Tralokinumab When Delivered as a 2 mL Injection at Different Flow Rates to Healthy Volunteers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02085473

Enrollment

Registered

2014-03-12

Start date

2014-03-19

Completion date

2014-07-10

Last updated

2018-12-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma, Healthy Subjects or Volunteers

Keywords

Asthma, Healthy Subjects or Volunteers, Tralokinumab, CAT-354

Brief summary

The primary objective of this study is to evaluate the pharmacokinetics (PK) and tolerability of tralokinumab when delivered subcutaneously at different flow rates to healthy volunteers.

Detailed description

This is a Phase 1, open-label, assessor-blind, parallel-group study to evaluate the PK and tolerability of a single subcutaneous dose of 300 milligram (mg) tralokinumab when delivered as a 2 milliliters (mL) injection at different flow rates to healthy adult volunteers.

Interventions

BIOLOGICALTralokinumab 300 mg

Participants will receive 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at different flow rates.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

19 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

Key Inclusion Criteria: * Healthy males and females ages 19-65 years * Body mass index of 19.0-30.0 kilogram per meter square (kg/m\^2) * No clinically significant abnormality * Vital signs, electrocardiogram (ECG), and laboratory parameters within normal range * Negative alcohol and drug screens * Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception * Nonsterilized males who are sexually active with a female partner of childbearing potential must use highly effective contraception. Key

Exclusion criteria

* Concurrent enrollment in another clinical study where the subject is receiving an investigational product * Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives prior to screening, whichever is longer * Receipt of any investigational nonbiologic agent within 3 months or 5 half-lives prior to screening, whichever is longer * Current use of regular pain-modifying, anti-depressant, anxiolytic, or hypnotic medication * History of thrombocytopenia or bleeding disorder or use of anticoagulants * History of any immunodeficiency disorder or use of immunosuppressive medication. * History of a clinically significant infection * History of cancer * Positive Hepatitis B or C * Positive HIV

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity])	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	AUC (0 - infinity) = Area under the serum concentration versus time curve (AUC) from time zero to infinite time, obtained from AUC (0 - t) plus AUC (t - infinity). Units are day\micrograms per millilitres = day\mcg/mL.
Maximum Observed Serum Concentration (Cmax)	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	The Cmax is the maximum observed serum concentration of tralokinumab.
Time to Maximum Concentration (Tmax)	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	Tmax is defined as actual sampling time to reach maximum observed tralokinumab concentration.
Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t])	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	AUC \[0-t\] is defined as area under the serum concentration-time curve from zero to last observed tralokinumab concentration.
Terminal Elimination Half-life (t1/2)	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	Terminal elimination half-life is the time measured for the serum concentration to decrease by one half. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Apparent Systemic Clearance (CL/F) After Subcutaneous Dose	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	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).
Apparent Terminal-Phase Volume of Distribution (Vz/F)	Day 1 (pre-dose sample collected within 30 minutes prior to study drug administration), Days 2, 4, 6, 8, 10, 15, 22, 36, and 57 post-dose	Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.

Secondary

Measure	Time frame	Description
Local Injection-Site Pain and Injection-Site Pruritus	During the injection until 72 hours post-injection for injection site-pain and immediately after administration of injection until 72 hours for injection-site pruritus	Local injection-site pain and pruritus intensity was rated on 0 to 100 millimeter (mm) visual analogue scale (VAS) at various time points, where 0 = no pain/ no pruritus; 100 = most severe pain/ most severe pruritus. Injection site pruritus intensity was assessed by the blinded assessor. Higher the score indicated higher intensity of pain and pruritus. Local injection site pain and pruritus was assessed at below time-points: 1 and 6 minute (min) during investigational product administration (IPA); immediately post IPA, 10, 20, 30, and 60 min, 2, 4, 8, 24 and 72 hour (h) post IPA.
Number of Participants Reporting Local Injection-Site Reactions	0, 10, 20, 30 and 60 minutes, 2, 4, 8, 24 and 72 hours post-injection	The signs and/or symptoms of local injection-site reactions including erythema, hematoma or bleeding, local warmth, swelling, and/or rash occurring within 72 hours post-injection were assessed and recorded by a blinded assessor.
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	From start of study drug administration up to Day 57	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 and important medical event. Treatment-emergent were events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants Reporting Treatment-emergent Adverse Events Related to Physical Examination	Day 1 to Day 57	The treatment-emergent adverse events related to physical examination were reported as per investigator discretion. Treatment-emergent were the events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants Reporting Treatment-emergent Adverse Events Related to Vital Signs	Day 1 to Day 57	Vital signs included systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and temperature. The treatment-emergent adverse events related to vital signs were reported as per investigator discretion. Treatment-emergent were the events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants Reporting Treatment-emergent Adverse Events in Laboratory Parameters	Day 1 to Day 57	Laboratory parameters included hematology, serum chemistry and urinalysis. The treatment-emergent adverse events in laboratory parameters were reported as per investigator discretion. Treatment-emergent were the events between administration of study drug and up to Day 57 that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants Exhibiting Anti-Drug Antibodies for Tralokinumab at Any Visit	Pre-dose on Day 1 and Day 57	Immunogenicity assessment included determination of anti-drug antibodies to tralokinumab (CAT-354) antibodies in serum samples.

Countries

United States

Participant flow

Recruitment details

This study was conducted between 19Mar2014 and 10Jul2014.

Pre-assignment details

A total of 149 participants were screened for the study, out of which 60 participants were randomized and completed in the study.

Participants by arm

Arm	Count
Cohort 1 Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 6 mL/min.	15
Cohort 2 Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 12 mL/min.	15
Cohort 3 Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 2 mL/min.	15
Cohort 4 Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 0.167 mL/min.	15
Total	60

Baseline characteristics

Characteristic	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Total
Age, Continuous	36.5 Years STANDARD_DEVIATION 9.5	39.7 Years STANDARD_DEVIATION 13.5	38.5 Years STANDARD_DEVIATION 14.1	38.4 Years STANDARD_DEVIATION 12.3	38.3 Years STANDARD_DEVIATION 12.2
Sex: Female, Male Female	7 Participants	7 Participants	8 Participants	8 Participants	30 Participants
Sex: Female, Male Male	8 Participants	8 Participants	7 Participants	7 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 15	0 / 15	0 / 15
other Total, other adverse events	5 / 15	5 / 15	4 / 15	4 / 15
serious Total, serious adverse events	0 / 15	0 / 15	0 / 15	0 / 15

Outcome results

Primary

Apparent Systemic Clearance (CL/F) After Subcutaneous Dose

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).