Study of Lanadelumab in Healthy Japanese and Matched Caucasian Adult Subjects

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT03401671
Collaborator
(none)
32
1
2
4.4
7.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK), safety and tolerability and pharmacodynamics (PD) of lanadelumab in healthy adult Japanese subjects and matched non-Hispanic healthy adult Caucasian subjects.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Pharmacodynamics of a Single Dose of Lanadelumab Administered Subcutaneously in Healthy Adult Japanese Subjects and Matched Healthy Adult Caucasian Subjects
Actual Study Start Date :
Jan 15, 2018
Actual Primary Completion Date :
May 30, 2018
Actual Study Completion Date :
May 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Japanese

Healthy subjects of Japanese descent will receive a single dose of 300 milligrams (mg) lanadelumab subcutaneous (SC) injection in the abdomen.

Drug: Lanadelumab
SC injection of 300mg in 2mL (150 mg/mL) solution of lanadelumab will be administered as a single dose injection in the abdomen.
Other Names:
  • SHP643
  • Experimental: Non-Hispanic Caucasians

    Healthy Non-Hispanic Caucasian subjects will receive a single dose of 300 mg lanadelumab SC injection in the abdomen

    Drug: Lanadelumab
    SC injection of 300mg in 2mL (150 mg/mL) solution of lanadelumab will be administered as a single dose injection in the abdomen.
    Other Names:
  • SHP643
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Observed Plasma Concentration (Cmax) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Cmax is the maximum observed plasma concentration of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    2. Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Tmax of Lanadelumab was presented.

    3. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    4. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      AUC(0-infinity) of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    5. Terminal Elimination Rate Constant (Lambda z) for Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Lambda z of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    6. Terminal Half-life (t12) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      t1/2 of Lanadelumab was presented.

    7. Apparent Clearance (CL/F) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    8. Apparent Volume of Distribution (Vz/F) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    9. Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Body-weight adjusted AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    10. Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Body-weight adjusted AUC(0-infinity) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    11. Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Body-weight adjusted Cmax of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    12. Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Body-weight adjusted CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    13. Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose]

      Body-weight adjusted Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.

    Secondary Outcome Measures

    1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality [From start of study drug administration up to follow-up (up to 115 days)]

      An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with onset at the time of or following the first exposure to study drug, or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. Severity of an AE is determined by following definitions: Mild: An event that does not generally interfere with usual activities of daily living; Moderate: An event that interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participants; Severe: An AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

    2. Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event [From start of study drug administration up to follow-up (up to 115 days)]

      Clinical laboratory assessments include hematology, clinical chemistry, coagulation and urinalysis. The investigator will assess out-of-range clinical laboratory values for clinical significance, to indicate whether or not the values are clinically significant. Any changes from baseline in clinical laboratory results which are deemed clinically significant by the investigator are to be recorded as an AE.

    3. Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event [From start of study drug administration up to follow-up (up to 115 days)]

      Vital sign assessments include blood pressure, pulse rate and body temperature. Any changes from baseline in vital signs which are deemed clinically significant by the investigator are to be recorded as an AE.

    4. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event [From start of study drug administration up to follow-up (up to 115 days)]

      Twelve-lead ECG will be performed after 5 minutes of rest in the supine position. Any change in ECG assessments which are deemed clinically significant by the investigator are to be reported as AE.

    5. Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points [Day 1, 14, 28, 56, and 112 (End of Study/Early Termination [EOS/ET])]

      Plasma samples were analyzed for presence of antidrug antibodies to lanadelumab. Participants who show positive results for lanadelumab antibodies were reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Ability to voluntarily provide written, signed, and dated informed consent as applicable to participate in the study.

    • An understanding, ability, and willingness to fully comply with study procedures and restrictions.

    • Age 18-55, inclusive, at the time of consent. The date of signature of the informed consent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the first screening visit.

    • Subjects must be either:

    1. A subject of Japanese descent born in Japan, who has resided outside of Japan for no longer than 5 years and is of Japanese parentage, defined as having 2 Japanese parents and 4 Japanese grandparents, all born in Japan.

    2. A non-Hispanic, Caucasian subject who has 2 non-Hispanic, Caucasian parents and 4 non-Hispanic, Caucasian grandparents.

    • 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.

    • Considered "healthy" by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, as well as a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.

    • Body mass index between 18.5-33 kilograms per square meter (kg/m^2), inclusive, with a body weight greater than or equal to (≥) 45 kg (99 pounds [lbs]). This inclusion criterion will only be assessed at the screening visit.

    • Willing and able to consume standardized meals during the confinement period of the study. All subjects will be required to consume the identical meals on study days when serial PK and PD blood samples are collected.

    Exclusion Criteria:
    • History 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 clinical or laboratory assessments.

    • Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to complete the study, or any condition that presents undue risk from the investigational product or procedures.

    • Known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients.

    • Significant illness, as judged by the investigator, within 2 weeks of the dose of investigational product.

    • Known history of alcohol or other substance abuse within the last year, per the investigator.

    • Donation of blood or blood products (example [e.g], plasma or platelets) within 60 days prior to receiving the dose of investigational product.

    • Within 30 days prior to the dose of investigational product:

    1. Have used an investigational product (if elimination half-life is less than [<] 6 days, otherwise 5 half-lives).

    2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.

    • Confirmed systolic blood pressure (BP) greater than (>) 139 millimeter of mercury (mmHg) or <89mmHg, and diastolic BP >89mmHg or <49mmHg.

    • Twelve-lead ECG values (average of triplicate readings) demonstrating QTc >450 milliseconds (msec) (males) or >470msec (females) at the Screening Visit or Day -1.

    • Positive screen for drugs of abuse (that is, amphetamines, benzodiazepines, barbiturates, cocaine, marijuana, opiates, phencyclidine) at Screening, or drugs of abuse or alcohol on Day -1.

    • Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. One alcohol unit=1 beer or 1 wine (5 ounce [oz]/150 milliliter [mL]) or 1 liquor (1.5oz/40mL) or 0.75oz alcohol.

    • Positive human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus.(HCV) antibody screen.

    • Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch, electronic). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the dose of investigational product.

    • Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6oz (180mL) cup of coffee, two 12oz (360mL) cans of cola, one 12oz cup of tea, and three 1oz (85g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine.

    • Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of hormonal replacement therapy or hormonal contraceptives). Current use is defined as use within 14 days of the dose of investigational product.

    • Abnormal laboratory values considered clinically significant, as determined by the investigator at Screening or Day -1.

    • History of any clinically significant surgery or procedure within 8 weeks of receiving the dose of investigational product, as determined by the investigator.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 WCCT Global, Inc. Cypress California United States 90630

    Sponsors and Collaborators

    • Shire

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT03401671
    Other Study ID Numbers:
    • SHP643-101
    First Posted:
    Jan 17, 2018
    Last Update Posted:
    Jun 3, 2021
    Last Verified:
    May 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
    Keywords provided by Shire

    Study Results

    Participant Flow

    Recruitment Details The study was conducted in the United States between 15 January 2018 (first participant first visit) and 30 May 2018 (last participant last visit).
    Pre-assignment Detail A total of 32 participants were enrolled, received the treatment and completed the study.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 milligrams (mg) lanadelumab subcutaneous (SC) injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Period Title: Overall Study
    STARTED 16 16
    COMPLETED 16 16
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Japanese Non-Hispanic Caucasians Total
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen. Total of all reporting groups
    Overall Participants 16 16 32
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    43.4
    (7.82)
    42.8
    (6.40)
    43.1
    (7.04)
    Sex: Female, Male (Count of Participants)
    Female
    10
    62.5%
    10
    62.5%
    20
    62.5%
    Male
    6
    37.5%
    6
    37.5%
    12
    37.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    16
    100%
    16
    100%
    32
    100%
    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
    16
    100%
    0
    0%
    16
    50%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    16
    100%
    16
    50%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
    Description Cmax is the maximum observed plasma concentration of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (ug/mL)]
    21.91
    (38)
    21.42
    (25)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Japanese, Non-Hispanic Caucasians
    Comments An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and ethnic group as a fixed effect.
    Type of Statistical Test Other
    Comments Analysis was performed for estimation of least square means only. Descriptive statistical analysis was the main analysis.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of Geometric least squares Means
    Estimated Value 1.0229
    Confidence Interval (2-Sided) 90%
    0.8473 to 1.2349
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab
    Description Tmax of Lanadelumab was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Median (Full Range) [day]
    5.67
    5.00
    3. Primary Outcome
    Title Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
    Description AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [day*microgram per milliliter(day*ug/mL)]
    510.6
    (30)
    547.6
    (20)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Japanese, Non-Hispanic Caucasians
    Comments An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and ethnic group as a fixed effect.
    Type of Statistical Test Other
    Comments Analysis was performed for estimation of least square means only. Descriptive statistical analysis was the main analysis.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of Geometric least squares Means
    Estimated Value 0.9324
    Confidence Interval (2-Sided) 90%
    0.8016 to 1.0846
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Primary Outcome
    Title Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab
    Description AUC(0-infinity) of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [day*microgram per milliliter(day* ug/mL)]
    515.0
    (30)
    552.7
    (20)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Japanese, Non-Hispanic Caucasians
    Comments An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and ethnic group as a fixed effect.
    Type of Statistical Test Other
    Comments Analysis was performed for estimation of least square means only. Descriptive statistical analysis was the main analysis.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Ratio of Geometric least squares Means
    Estimated Value 0.9318
    Confidence Interval (2-Sided) 90%
    0.8005 to 1.0846
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Primary Outcome
    Title Terminal Elimination Rate Constant (Lambda z) for Lanadelumab
    Description Lambda z of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [per day]
    0.04470
    (9)
    0.04385
    (11)
    6. Primary Outcome
    Title Terminal Half-life (t12) of Lanadelumab
    Description t1/2 of Lanadelumab was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Median (Full Range) [day]
    15.54
    15.59
    7. Primary Outcome
    Title Apparent Clearance (CL/F) of Lanadelumab
    Description CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [liter per day]
    0.5826
    (30)
    0.5428
    (20)
    8. Primary Outcome
    Title Apparent Volume of Distribution (Vz/F) of Lanadelumab
    Description Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [liter]
    13.03
    (29)
    12.38
    (22)
    9. Primary Outcome
    Title Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
    Description Body-weight adjusted AUC(0-last) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [day*ug/mL/kg]
    510.6
    (30)
    547.6
    (20)
    10. Primary Outcome
    Title Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab
    Description Body-weight adjusted AUC(0-infinity) of Lanadelumab was presented. Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [day*ug/mL/kg]
    8.012
    (44)
    7.950
    (27)
    11. Primary Outcome
    Title Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
    Description Body-weight adjusted Cmax of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Median (Full Range) [microgram per milliliter per kilogram]
    0.3236
    0.3042
    12. Primary Outcome
    Title Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab
    Description Body-weight adjusted CL/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [liter per day per kilogram (L/day/kg)]
    0.009064
    (23)
    0.007809
    (20)
    13. Primary Outcome
    Title Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab
    Description Body-weight adjusted Vz/F of Lanadelumab was presented.Geometric mean and geometric coefficient of variation percent (CV%) was presented.
    Time Frame Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK set consisted of all participants who received at least 1 dose of lanadelumab and had at least 1 evaluable post-dose PK concentration value.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Geometric Mean (Geometric Coefficient of Variation) [liter per kilogram (L/kg)]
    0.2028
    (23)
    0.1781
    (20)
    14. Secondary Outcome
    Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality
    Description An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with onset at the time of or following the first exposure to study drug, or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. Severity of an AE is determined by following definitions: Mild: An event that does not generally interfere with usual activities of daily living; Moderate: An event that interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participants; Severe: An AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.
    Time Frame From start of study drug administration up to follow-up (up to 115 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received at least 1 dose of Lanadelumab.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Participants with Mild TEAE
    6
    37.5%
    4
    25%
    Participants with Moderate TEAE
    1
    6.3%
    5
    31.3%
    Participants with Severe TEAE
    0
    0%
    0
    0%
    Participants with Serious TEAE
    0
    0%
    0
    0%
    Participants with Non-Serious TEAE
    7
    43.8%
    9
    56.3%
    Participants with Causality (Death)
    0
    0%
    0
    0%
    15. Secondary Outcome
    Title Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event
    Description Clinical laboratory assessments include hematology, clinical chemistry, coagulation and urinalysis. The investigator will assess out-of-range clinical laboratory values for clinical significance, to indicate whether or not the values are clinically significant. Any changes from baseline in clinical laboratory results which are deemed clinically significant by the investigator are to be recorded as an AE.
    Time Frame From start of study drug administration up to follow-up (up to 115 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received at least 1 dose of Lanadelumab.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Count of Participants [Participants]
    0
    0%
    0
    0%
    16. Secondary Outcome
    Title Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event
    Description Vital sign assessments include blood pressure, pulse rate and body temperature. Any changes from baseline in vital signs which are deemed clinically significant by the investigator are to be recorded as an AE.
    Time Frame From start of study drug administration up to follow-up (up to 115 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received at least 1 dose of Lanadelumab.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Count of Participants [Participants]
    0
    0%
    0
    0%
    17. Secondary Outcome
    Title Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event
    Description Twelve-lead ECG will be performed after 5 minutes of rest in the supine position. Any change in ECG assessments which are deemed clinically significant by the investigator are to be reported as AE.
    Time Frame From start of study drug administration up to follow-up (up to 115 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set includes all participants who received at least 1 dose of Lanadelumab.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Count of Participants [Participants]
    0
    0%
    0
    0%
    18. Secondary Outcome
    Title Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points
    Description Plasma samples were analyzed for presence of antidrug antibodies to lanadelumab. Participants who show positive results for lanadelumab antibodies were reported.
    Time Frame Day 1, 14, 28, 56, and 112 (End of Study/Early Termination [EOS/ET])

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who received at least 1 dose of lanadelumab.
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    Measure Participants 16 16
    Participants with positive ADA: Day 1
    0
    0%
    0
    0%
    Participants with positive ADA: Day 14
    0
    0%
    0
    0%
    Participants with positive ADA: Day 28
    0
    0%
    0
    0%
    Participants with positive ADA: Day 56
    0
    0%
    0
    0%
    Participants with positive ADA: Day 112 (EOS/ET)
    0
    0%
    1
    6.3%

    Adverse Events

    Time Frame From start of study drug administration up to follow-up (up to 115 days)
    Adverse Event Reporting Description
    Arm/Group Title Japanese Non-Hispanic Caucasians
    Arm/Group Description Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen.
    All Cause Mortality
    Japanese Non-Hispanic Caucasians
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/16 (0%)
    Serious Adverse Events
    Japanese Non-Hispanic Caucasians
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Japanese Non-Hispanic Caucasians
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/16 (43.8%) 9/16 (56.3%)
    Gastrointestinal disorders
    Abdominal pain 1/16 (6.3%) 1 0/16 (0%) 0
    Constipation 1/16 (6.3%) 1 0/16 (0%) 0
    Nausea 0/16 (0%) 0 2/16 (12.5%) 2
    General disorders
    Injection site erythema 1/16 (6.3%) 1 0/16 (0%) 0
    Injection site pain 0/16 (0%) 0 1/16 (6.3%) 1
    Vessel puncture site pain 1/16 (6.3%) 1 0/16 (0%) 0
    Infections and infestations
    Nasopharyngitis 0/16 (0%) 0 1/16 (6.3%) 1
    Pharyngitis 0/16 (0%) 0 2/16 (12.5%) 2
    Rhinitis 0/16 (0%) 0 1/16 (6.3%) 1
    Upper respiratory tract infection 1/16 (6.3%) 1 3/16 (18.8%) 3
    Viral upper respiratory tract infection 0/16 (0%) 0 1/16 (6.3%) 1
    Injury, poisoning and procedural complications
    Animal bite 0/16 (0%) 0 1/16 (6.3%) 1
    Arthropod bite 1/16 (6.3%) 1 0/16 (0%) 0
    Contusion 0/16 (0%) 0 1/16 (6.3%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/16 (6.3%) 1 0/16 (0%) 0
    Back pain 0/16 (0%) 0 2/16 (12.5%) 2
    Nervous system disorders
    Headache 1/16 (6.3%) 1 2/16 (12.5%) 3
    Radiculopathy 0/16 (0%) 0 1/16 (6.3%) 1
    Syncope 0/16 (0%) 0 1/16 (6.3%) 1
    Tension headache 0/16 (0%) 0 1/16 (6.3%) 1
    Reproductive system and breast disorders
    Dysmenorrhoea 0/16 (0%) 0 2/16 (12.5%) 2
    Respiratory, thoracic and mediastinal disorders
    Sinus congestion 0/16 (0%) 0 1/16 (6.3%) 1
    Skin and subcutaneous tissue disorders
    Dermatitis atopic 1/16 (6.3%) 1 0/16 (0%) 0
    Dry skin 0/16 (0%) 0 1/16 (6.3%) 1

    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 Shire
    Phone +1 866 842 5335
    Email ClinicalTransparency@shire.com
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT03401671
    Other Study ID Numbers:
    • SHP643-101
    First Posted:
    Jan 17, 2018
    Last Update Posted:
    Jun 3, 2021
    Last Verified:
    May 1, 2021