Healthy Volunteers
Conditions
Keywords
Lanadelumab
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.
Interventions
DRUGLanadelumab
SC injection of 300mg in 2mL (150 mg/mL) solution of lanadelumab will be administered as a single dose injection in the abdomen.
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
A total of 32 participants were enrolled, received the treatment and completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Japanese Healthy participants of Japanese descent received a single dose of 300 mg lanadelumab SC injection in the abdomen. | 16 |
| Non-Hispanic Caucasians Healthy Non-Hispanic Caucasian participants received a single dose of 300 mg lanadelumab SC injection in the abdomen. | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Non-Hispanic Caucasians | Total | Japanese |
|---|---|---|---|
| Age, Continuous | 42.8 Years STANDARD_DEVIATION 6.4 | 43.1 Years STANDARD_DEVIATION 7.04 | 43.4 Years STANDARD_DEVIATION 7.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 32 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 16 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 16 Participants | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 7 / 16 | 9 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Apparent Clearance (CL/F) of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Apparent Clearance (CL/F) of Lanadelumab | 0.5826 liter per day | Geometric Coefficient of Variation 30 |
| Non-Hispanic Caucasians | Apparent Clearance (CL/F) of Lanadelumab | 0.5428 liter per day | Geometric Coefficient of Variation 20 |
Primary
Apparent Volume of Distribution (Vz/F) of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Apparent Volume of Distribution (Vz/F) of Lanadelumab | 13.03 liter | Geometric Coefficient of Variation 29 |
| Non-Hispanic Caucasians | Apparent Volume of Distribution (Vz/F) of Lanadelumab | 12.38 liter | Geometric Coefficient of Variation 22 |
Primary
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab | 515.0 day*microgram per milliliter(day* ug/mL) | Geometric Coefficient of Variation 30 |
| Non-Hispanic Caucasians | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab | 552.7 day*microgram per milliliter(day* ug/mL) | Geometric Coefficient of Variation 20 |
Comparison: An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and ethnic group as a fixed effect.90% CI: [0.8005, 1.0846]
Primary
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab | 510.6 day*microgram per milliliter(day*ug/mL) | Geometric Coefficient of Variation 30 |
| Non-Hispanic Caucasians | Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab | 547.6 day*microgram per milliliter(day*ug/mL) | Geometric Coefficient of Variation 20 |
Comparison: An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and ethnic group as a fixed effect.90% CI: [0.8016, 1.0846]
Primary
Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab | 0.009064 liter per day per kilogram (L/day/kg) | Geometric Coefficient of Variation 23 |
| Non-Hispanic Caucasians | Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab | 0.007809 liter per day per kilogram (L/day/kg) | Geometric Coefficient of Variation 20 |
Primary
Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab | 0.2028 liter per kilogram (L/kg) | Geometric Coefficient of Variation 23 |
| Non-Hispanic Caucasians | Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab | 0.1781 liter per kilogram (L/kg) | Geometric Coefficient of Variation 20 |
Primary
Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab | 8.012 day*ug/mL/kg | Geometric Coefficient of Variation 44 |
| Non-Hispanic Caucasians | Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab | 7.950 day*ug/mL/kg | Geometric Coefficient of Variation 27 |
Primary
Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab | 510.6 day*ug/mL/kg | Geometric Coefficient of Variation 30 |
| Non-Hispanic Caucasians | Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab | 547.6 day*ug/mL/kg | Geometric Coefficient of Variation 20 |
Primary
Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Japanese | Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab | 0.3236 microgram per milliliter per kilogram |
| Non-Hispanic Caucasians | Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab | 0.3042 microgram per milliliter per kilogram |
Primary
Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Maximum Observed Plasma Concentration (Cmax) of Lanadelumab | 21.91 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 38 |
| Non-Hispanic Caucasians | Maximum Observed Plasma Concentration (Cmax) of Lanadelumab | 21.42 microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 25 |
Comparison: An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and ethnic group as a fixed effect.90% CI: [0.8473, 1.2349]
Primary
Terminal Elimination Rate Constant (Lambda z) for Lanadelumab
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese | Terminal Elimination Rate Constant (Lambda z) for Lanadelumab | 0.04470 per day | Geometric Coefficient of Variation 9 |
| Non-Hispanic Caucasians | Terminal Elimination Rate Constant (Lambda z) for Lanadelumab | 0.04385 per day | Geometric Coefficient of Variation 11 |
Primary
Terminal Half-life (t12) of Lanadelumab
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Japanese | Terminal Half-life (t12) of Lanadelumab | 15.54 day |
| Non-Hispanic Caucasians | Terminal Half-life (t12) of Lanadelumab | 15.59 day |
Primary
Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Japanese | Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab | 5.67 day |
| Non-Hispanic Caucasians | Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab | 5.00 day |
Secondary
Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points
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])
Population: Safety analysis set included all participants who received at least 1 dose of lanadelumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Japanese | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 14 | 0 Participants |
| Japanese | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 56 | 0 Participants |
| Japanese | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 28 | 0 Participants |
| Japanese | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 112 (EOS/ET) | 0 Participants |
| Japanese | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 1 | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 112 (EOS/ET) | 1 Participants |
| Non-Hispanic Caucasians | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 1 | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 14 | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 28 | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points | Participants with positive ADA: Day 56 | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event
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)
Population: Safety analysis set included all participants who received at least 1 dose of Lanadelumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese | Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event
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)
Population: Safety analysis set includes all participants who received at least 1 dose of Lanadelumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event
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)
Population: Safety analysis set included all participants who received at least 1 dose of Lanadelumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese | Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality
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)
Population: Safety analysis set included all participants who received at least 1 dose of Lanadelumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Japanese | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Mild TEAE | 6 Participants |
| Japanese | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Moderate TEAE | 1 Participants |
| Japanese | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Severe TEAE | 0 Participants |
| Japanese | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Serious TEAE | 0 Participants |
| Japanese | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Non-Serious TEAE | 7 Participants |
| Japanese | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Causality (Death) | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Non-Serious TEAE | 9 Participants |
| Non-Hispanic Caucasians | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Mild TEAE | 4 Participants |
| Non-Hispanic Caucasians | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Serious TEAE | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Moderate TEAE | 5 Participants |
| Non-Hispanic Caucasians | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Causality (Death) | 0 Participants |
| Non-Hispanic Caucasians | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality | Participants with Severe TEAE | 0 Participants |