Phase 1
Completed N=32
Study of Lanadelumab in Healthy Japanese and Matched Caucasian Adult Subjects
Healthy Volunteers
Source: ClinicalTrials.gov NCT03401671 ↗
Enrolled (actual)
32
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) of Lanadelumab — 21.91; 21.42 microgram per milliliter (ug/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Lanadelumab |
21.91; 21.42 | — |
| PRIMARY Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab |
5.67; 5.00 | — |
| PRIMARY Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab |
510.6; 547.6 | — |
| PRIMARY Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab |
515.0; 552.7 | — |
| PRIMARY Terminal Elimination Rate Constant (Lambda z) for Lanadelumab |
0.04470; 0.04385 | — |
| PRIMARY Terminal Half-life (t12) of Lanadelumab |
15.54; 15.59 | — |
| PRIMARY Apparent Clearance (CL/F) of Lanadelumab |
0.5826; 0.5428 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of Lanadelumab |
13.03; 12.38 | — |
| PRIMARY 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; 547.6 | — |
| PRIMARY Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) in Plasma of Lanadelumab |
8.012; 7.950 | — |
| PRIMARY Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab |
0.3236; 0.3042 | — |
| PRIMARY Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab |
0.009064; 0.007809 | — |
| PRIMARY Body-weight Adjusted Apparent Volume of Distribution (Vz/F) of Lanadelumab |
0.2028; 0.1781 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality |
6; 4; 1; 5; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event |
0; 0 | — |
| SECONDARY Number of Participants Who Developed Antidrug Antibodies to Lanadelumab at Specified Time Points |
0; 0; 0; 0; 0; 0 | — |
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:
- 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.
- 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:
- Have used an investigational product (if elimination half-life is less than [ ) 139 millimeter of mercury (mmHg) or 89mmHg or 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 c
Data sourced from ClinicalTrials.gov (NCT03401671). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.