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

NCT04503603 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TAK-743-1003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (14)

• 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

Study Arms (2)

Lanadelumab 300 mg

EXPERIMENTAL

Participants will receive single dose of lanadelumab 300 mg intravenous (IV) infusion on Day 1 followed by second dose on Day 4.

Drug: Lanadelumab

Placebo

PLACEBO COMPARATOR

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

Interventions

Lanadelumab DRUG

Participants will receive lanadelumab 300 mg IV infusion on Day 1 followed by Day 4.

Also known as: TAK-743

Lanadelumab 300 mg

Placebo OTHER

Participants will receive placebo matching to lanadelumab IV infusion on Day 1 followed by Day 4.

Placebo

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (1)

Celerion

Lincoln, Nebraska, 68502, United States

Location

Related Links

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

MeSH Terms

Interventions

lanadelumab

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda Development Center Americas, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: August 10, 2020
• Primary Completion: December 23, 2020
• Study Completion: December 23, 2020
• Last Updated: March 7, 2022
• Results First Posted: March 7, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

US (1)