A Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Participants

A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Subjects

The purpose of this study to evaluate the safety, tolerability and pharmacokinetics (PK) of lanadelumab administered by Intravenous (IV) infusion in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Lanadelumab; Other: Placebo

Detailed Description

A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Subjects

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, adult, male or female, 19-55 years of age, inclusive, at screening.
• Continuous non-smoker who has not used nicotine-containing products for at least 30 days prior to the first dosing and throughout the study, based on participant self-reporting.
• Body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 32.0 kilogram per square meter (kg/m^2) at screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), per the investigator.
• Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
• Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.

Exclusion Criteria:

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease per the investigator.
• History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study, per the investigator.
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing per the investigator.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
• History or presence of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinically significant clinical or laboratory assessments per the investigator.
• Female participants with a positive pregnancy test or lactating.
• Positive urine drug or alcohol results at screening.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Supine blood pressure is less than 90/40 millimetre of mercury (mmHg) or greater than 140/90 mmHg at screening.
• Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
• Orthostatic vital sign results with a decrease in systolic greater than (>) 20 mmHg or decrease in diastolic > 10 mmHg and increase in pulse of > 20 beats per minute.
• QTcF interval is > 450 milliseconds (msec) (males) or > 470 msec (females) or ECG findings are deemed abnormal with clinical significance at screening per the investigator.
• Estimated creatinine clearance less than (<) 80 milliliters per minute (mL/min) at screening.
• Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration. After randomization/dosing, a nonsteroidal anti-inflammatory drug may be administered at the discretion of the investigator. Hormone replacement therapy will also be allowed if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration.
• Has been on a diet incompatible with the on-study diet, per the investigator, within the 30 days prior to the first dosing and throughout the study.
• Donation of blood or significant blood loss within 56 days prior to the first dosing.
• Plasma donation within 7 days prior to the first dosing.
• Participation in another clinical study within 30 days or 5 half-lives prior to the first dosing. The 30-day window or 5 half-lives will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lanadelumab 300 mg; Participants will receive single dose of lanadelumab 300 mg intravenous (IV) infusion on Day 1 followed by second dose on Day 4.	Drug: Lanadelumab; Participants will receive lanadelumab 300 mg IV infusion on Day 1 followed by Day 4.; Other Names: TAK-743
PLACEBO_COMPARATOR: Placebo; Participant will receive single dose of lanadelumab matching placebo (normal saline) IV infusion on Day 1 followed by second dose on Day 4.	Other: Placebo; Participants will receive placebo matching to lanadelumab IV infusion on Day 1 followed by Day 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study that did not necessarily have a causal relationship with the treatment. TEAEs were events that occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs were reported.	From the first dose of study treatment up to the end of study (Day 112)
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters	Clinical laboratory assessment included hematology, clinical chemistry, coagulation, and urinalysis. Any changes in clinical laboratory results that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant change from baseline in laboratory values were reported.	From the first dose of study treatment up to the end of study (Day 112)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature (oral). Any changes in vital signs that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant change from baseline in vital signs were reported.	From the first dose of study treatment up to the end of study (Day 112)
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings	12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. Any changes in ECG parameters that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.	From the first dose of study treatment up to the end of study (Day 112)
AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration for Lanadelumab	AUC0-last for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
AUC0-inf: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity for Lanadelumab	AUC0-inf for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
Cmax1: Maximum Observed Plasma Concentration Following the First IV Dose for Lanadelumab	Cmax1 following the first IV dose for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
Cmax2: Maximum Observed Plasma Concentration Following the Second IV Dose for Lanadelumab	Cmax2 following the second IV dose for lanadelumab was reported.	Pre-dose (Day 4) up to 2592 hours post-dose
Tmax1: Minimum Observed Time to Reach the First Cmax1 for Lanadelumab	Tmax1 following the first IV dose for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
Tmax2: Minimum Observed Time to Reach the Second Cmax2 for Lanadelumab	Tmax2 following the second IV dose for lanadelumab was reported.	Pre-dose (Day 4) up to 2592 hours post-dose
Terminal Half-Life (T1/2) of Lanadelumab in Plasma	T1/2 is defined as the time required for the concentration of the drug to reach half of its original value. T1/2 for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
Clearance (CL) of Lanadelumab in Plasma	Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
Vss: Volume of Distribution at Steady State in Plasma for Lanadelumab	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 plasma concentration of a drug. Vss for lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose
First Order Elimination Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of Lanadelumab	Lambda z of Lanadelumab was reported.	Pre-dose (Day 1) up to 2664 hours post-dose

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 10, 2020
• Primary Completion (ACTUAL): December 23, 2020
• Study Completion (ACTUAL): December 23, 2020

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (ACTUAL): August 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: TAK-743-1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No