Clinical trial NCT03401671: Study of Lanadelumab in Healthy Japanese and Matched Caucasian Adult Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Lanadelumab
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-01-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Terminal Elimination Rate Constant (Lambda z) for Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Terminal Half-life (t12) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Apparent Clearance (CL/F) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
measure: Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality
timeFrame: From start of study drug administration up to follow-up (up to 115 days)
measure: Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event
timeFrame: From start of study drug administration up to follow-up (up to 115 days)
measure: Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event
timeFrame: From start of study drug administration up to follow-up (up to 115 days)
measure: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event
timeFrame: From start of study drug administration up to follow-up (up to 115 days)
measure: Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points
timeFrame: Day 1, 14, 28, 56, and 112 (End of Study/Early Termination [EOS/ET])
Other outcomes:
Locations:
city: Cypress
country: United States
facility: WCCT Global, Inc.
state: California
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: