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

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT04503603
Collaborator
Takeda Development Center Americas, Inc. (Industry)
12
1
2
4.4
2.7

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Aug 10, 2020
Actual Primary Completion Date :
Dec 23, 2020
Actual Study Completion Date :
Dec 23, 2020

Arms and Interventions

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.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [From the first dose of study treatment up to the end of study (Day 112)]

      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.

    2. Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters [From the first dose of study treatment up to the end of study (Day 112)]

      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.

    3. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [From the first dose of study treatment up to the end of study (Day 112)]

      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.

    4. Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings [From the first dose of study treatment up to the end of study (Day 112)]

      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.

    5. AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration for Lanadelumab [Pre-dose (Day 1) up to 2664 hours post-dose]

      AUC0-last for lanadelumab was reported.

    6. AUC0-inf: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity for Lanadelumab [Pre-dose (Day 1) up to 2664 hours post-dose]

      AUC0-inf for lanadelumab was reported.

    7. Cmax1: Maximum Observed Plasma Concentration Following the First IV Dose for Lanadelumab [Pre-dose (Day 1) up to 2664 hours post-dose]

      Cmax1 following the first IV dose for lanadelumab was reported.

    8. Cmax2: Maximum Observed Plasma Concentration Following the Second IV Dose for Lanadelumab [Pre-dose (Day 4) up to 2592 hours post-dose]

      Cmax2 following the second IV dose for lanadelumab was reported.

    9. Tmax1: Minimum Observed Time to Reach the First Cmax1 for Lanadelumab [Pre-dose (Day 1) up to 2664 hours post-dose]

      Tmax1 following the first IV dose for lanadelumab was reported.

    10. Tmax2: Minimum Observed Time to Reach the Second Cmax2 for Lanadelumab [Pre-dose (Day 4) up to 2592 hours post-dose]

      Tmax2 following the second IV dose for lanadelumab was reported.

    11. Terminal Half-Life (T1/2) of Lanadelumab in Plasma [Pre-dose (Day 1) up to 2664 hours post-dose]

      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.

    12. Clearance (CL) of Lanadelumab in Plasma [Pre-dose (Day 1) up to 2664 hours post-dose]

      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.

    13. Vss: Volume of Distribution at Steady State in Plasma for Lanadelumab [Pre-dose (Day 1) up to 2664 hours post-dose]

      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.

    14. First Order Elimination Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of Lanadelumab [Pre-dose (Day 1) up to 2664 hours post-dose]

      Lambda z of Lanadelumab was reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Celerion Lincoln Nebraska United States 68502

    Sponsors and Collaborators

    • Takeda
    • Takeda Development Center Americas, Inc.

    Investigators

    • Study Director: Study Director, Takeda Development Center Americas, Inc.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT04503603
    Other Study ID Numbers:
    • TAK-743-1003
    First Posted:
    Aug 7, 2020
    Last Update Posted:
    Mar 7, 2022
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 1 investigative site in the United States between 10 August 2020 (first participant first visit) and 23 December 2020 (last participant last visit).
    Pre-assignment Detail A total of 12 healthy participants were enrolled and randomized to receive lanadelumab 300 milligrams (mg) or matching placebo in this study.
    Arm/Group Title Lanadelumab 300 mg Placebo
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg intravenous (IV) infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of lanadelumab matching placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
    Period Title: Overall Study
    STARTED 9 3
    COMPLETED 9 3
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Lanadelumab 300 mg Placebo Total
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4. Total of all reporting groups
    Overall Participants 9 3 12
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    34.3
    (11.73)
    42.0
    (10.44)
    36.3
    (11.48)
    Sex: Female, Male (Count of Participants)
    Female
    4
    44.4%
    1
    33.3%
    5
    41.7%
    Male
    5
    55.6%
    2
    66.7%
    7
    58.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    33.3%
    1
    8.3%
    Not Hispanic or Latino
    9
    100%
    2
    66.7%
    11
    91.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    22.2%
    0
    0%
    2
    16.7%
    White
    5
    55.6%
    3
    100%
    8
    66.7%
    More than one race
    2
    22.2%
    0
    0%
    2
    16.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
    Description 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.
    Time Frame From the first dose of study treatment up to the end of study (Day 112)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
    Arm/Group Title Lanadelumab 300 mg Placebo
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9 3
    Count of Participants [Participants]
    7
    77.8%
    2
    66.7%
    2. Primary Outcome
    Title Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
    Description 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.
    Time Frame From the first dose of study treatment up to the end of study (Day 112)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
    Arm/Group Title Lanadelumab 300 mg Placebo
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9 3
    Count of Participants [Participants]
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Number of Participants With Clinically Significant Change From Baseline in Vital Signs
    Description 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.
    Time Frame From the first dose of study treatment up to the end of study (Day 112)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
    Arm/Group Title Lanadelumab 300 mg Placebo
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9 3
    Count of Participants [Participants]
    0
    0%
    0
    0%
    4. Primary Outcome
    Title Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
    Description 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.
    Time Frame From the first dose of study treatment up to the end of study (Day 112)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
    Arm/Group Title Lanadelumab 300 mg Placebo
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9 3
    Count of Participants [Participants]
    0
    0%
    0
    0%
    5. Primary Outcome
    Title AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration for Lanadelumab
    Description AUC0-last for lanadelumab was reported.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [hour*microgram per milliliter (h*mcg/mL)]
    32955
    (10.5)
    6. Primary Outcome
    Title AUC0-inf: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity for Lanadelumab
    Description AUC0-inf for lanadelumab was reported.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [h*mcg/mL]
    33305
    (10.5)
    7. Primary Outcome
    Title Cmax1: Maximum Observed Plasma Concentration Following the First IV Dose for Lanadelumab
    Description Cmax1 following the first IV dose for lanadelumab was reported.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (mcg/mL)]
    75.6
    (16.1)
    8. Primary Outcome
    Title Cmax2: Maximum Observed Plasma Concentration Following the Second IV Dose for Lanadelumab
    Description Cmax2 following the second IV dose for lanadelumab was reported.
    Time Frame Pre-dose (Day 4) up to 2592 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]
    120
    (20.7)
    9. Primary Outcome
    Title Tmax1: Minimum Observed Time to Reach the First Cmax1 for Lanadelumab
    Description Tmax1 following the first IV dose for lanadelumab was reported.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Median (Full Range) [hours]
    2.01
    10. Primary Outcome
    Title Tmax2: Minimum Observed Time to Reach the Second Cmax2 for Lanadelumab
    Description Tmax2 following the second IV dose for lanadelumab was reported.
    Time Frame Pre-dose (Day 4) up to 2592 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Median (Full Range) [hours]
    74.03
    11. Primary Outcome
    Title Terminal Half-Life (T1/2) of Lanadelumab in Plasma
    Description 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.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Median (Full Range) [days]
    19.3
    12. Primary Outcome
    Title Clearance (CL) of Lanadelumab in Plasma
    Description 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.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [milliliter per hour (mL/h)]
    18.1
    (10.4)
    13. Primary Outcome
    Title Vss: Volume of Distribution at Steady State in Plasma for Lanadelumab
    Description 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.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [milliliter (mL)]
    8070
    (19.5)
    14. Primary Outcome
    Title First Order Elimination Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of Lanadelumab
    Description Lambda z of Lanadelumab was reported.
    Time Frame Pre-dose (Day 1) up to 2664 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
    Arm/Group Title Lanadelumab 300 mg
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
    Measure Participants 9
    Geometric Mean (Geometric Coefficient of Variation) [Per hour (/h)]
    9.90
    (31.0)

    Adverse Events

    Time Frame From the first dose of study treatment up to the end of study (Day 112)
    Adverse Event Reporting Description
    Arm/Group Title Lanadelumab 300 mg Placebo
    Arm/Group Description Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4. Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
    All Cause Mortality
    Lanadelumab 300 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/9 (0%) 0/3 (0%)
    Serious Adverse Events
    Lanadelumab 300 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/9 (0%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Lanadelumab 300 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/9 (77.8%) 2/3 (66.7%)
    Gastrointestinal disorders
    Abdominal pain upper 2/9 (22.2%) 2 0/3 (0%) 0
    Constipation 1/9 (11.1%) 1 1/3 (33.3%) 1
    Diarrhoea 0/9 (0%) 0 1/3 (33.3%) 2
    Nausea 1/9 (11.1%) 1 0/3 (0%) 0
    Vomiting 1/9 (11.1%) 1 0/3 (0%) 0
    General disorders
    Catheter site pain 1/9 (11.1%) 1 0/3 (0%) 0
    Infections and infestations
    Cystitis 1/9 (11.1%) 1 0/3 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 1/9 (11.1%) 1 1/3 (33.3%) 1
    Muscle spasms 0/9 (0%) 0 1/3 (33.3%) 1
    Musculoskeletal discomfort 0/9 (0%) 0 1/3 (33.3%) 1
    Nervous system disorders
    Headache 2/9 (22.2%) 4 1/3 (33.3%) 2
    Paraesthesia 1/9 (11.1%) 1 0/3 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea 1/9 (11.1%) 1 0/3 (0%) 0
    Skin and subcutaneous tissue disorders
    Blister 0/9 (0%) 0 1/3 (33.3%) 1
    Rash papular 1/9 (11.1%) 1 0/3 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.

    Results Point of Contact

    Name/Title Study Director
    Organization Takeda
    Phone +1-877-825-3327
    Email TrialDisclosures@takeda.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT04503603
    Other Study ID Numbers:
    • TAK-743-1003
    First Posted:
    Aug 7, 2020
    Last Update Posted:
    Mar 7, 2022
    Last Verified:
    Dec 1, 2021