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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02085473
• Other study ID #: D2210C00011
• Status: Completed
• Phase: Phase 1
• Start date: March 19, 2014
• Est. completion date: July 10, 2014

Study information

• Verified date: December 2018
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 10, 2014
• Est. primary completion date: July 10, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Healthy Subjects or Volunteers

Intervention

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

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska
United States	Research Site	Lincoln	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

Jain M, Doughty D, Clawson C, Li X, White N, Agoram B, van der Merwe R. Tralokinumab pharmacokinetics and tolerability when administered by different subcutaneous injection methods and rates . Int J Clin Pharmacol Ther. 2017 Jul;55(7):606-620. doi: 10.5414/CP203023. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity])	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.	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
Primary	Maximum Observed Serum Concentration (Cmax)	The Cmax is the maximum observed serum concentration of tralokinumab.	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
Primary	Time to Maximum Concentration (Tmax)	Tmax is defined as actual sampling time to reach maximum observed tralokinumab concentration.	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
Primary	Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUC [0-t])	AUC [0-t] is defined as area under the serum concentration-time curve from zero to last observed tralokinumab concentration.	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
Primary	Terminal Elimination Half-life (t1/2)	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).	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
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).	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
Primary	Apparent Terminal-Phase Volume of Distribution (Vz/F)	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.	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
Secondary	Local Injection-Site Pain and 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.	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
Secondary	Number of Participants Reporting Local Injection-Site Reactions	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.	0, 10, 20, 30 and 60 minutes, 2, 4, 8, 24 and 72 hours post-injection
Secondary	Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	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.	From start of study drug administration up to Day 57
Secondary	Number of Participants Reporting Treatment-emergent Adverse Events Related to Physical Examination	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.	Day 1 to Day 57
Secondary	Number of Participants Reporting Treatment-emergent Adverse Events Related to Vital Signs	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.	Day 1 to Day 57
Secondary	Number of Participants Reporting Treatment-emergent Adverse Events in Laboratory Parameters	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.	Day 1 to Day 57
Secondary	Number of Participants Exhibiting Anti-Drug Antibodies for Tralokinumab at Any Visit	Immunogenicity assessment included determination of anti-drug antibodies to tralokinumab (CAT-354) antibodies in serum samples.	Pre-dose on Day 1 and Day 57

External Links

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