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

Phase 1

Completed

Conditions: Healthy Subjects or Volunteers
Asthma

Interventions: Biological: Tralokinumab 300 mg

Registration Number: NCT02085473

Lead Sponsor: MedImmune LLC

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Tralokinumab 300 mg	Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'W' mL/min.
Cohort 3	Tralokinumab 300 mg	Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'Y' mL/min.
Cohort 4	Tralokinumab 300 mg	Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'Z' mL/min.
Cohort 2	Tralokinumab 300 mg	Participants received 300 milligram (mg) tralokinumab when delivered as a 2 milliliter (mL) subcutaneous injection at a flow rate of 'X' mL/min.

Primary Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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).

Secondary Outcome Measures

Name	Time	Method
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.
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 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 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.
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.