Study of Lanadelumab in Healthy Japanese and Matched Caucasian Adult Subjects

NCT03401671 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SHP643-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Lanadelumab

Outcome Measures

Primary Outcomes (13)

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab

  Tmax of Lanadelumab was presented.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• Terminal Half-life (t12) of Lanadelumab

  t1/2 of Lanadelumab was presented.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• Apparent Clearance (CL/F) of Lanadelumab

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

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

• 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.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016 and 2688 hours post-dose

Secondary Outcomes (5)

• 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)

• 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)

• 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)

• 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)

• 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])

Study Arms (2)

Japanese

EXPERIMENTAL

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

Drug: Lanadelumab

Non-Hispanic Caucasians

EXPERIMENTAL

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

Drug: Lanadelumab

Interventions

Lanadelumab DRUG

SC injection of 300mg in 2mL (150 mg/mL) solution of lanadelumab will be administered as a single dose injection in the abdomen.

Also known as: SHP643

Japanese; Non-Hispanic Caucasians

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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 \[\<\] 6 days, otherwise 5 half-lives).
• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

WCCT Global, Inc.

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

lanadelumab

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2018
• First Posted: January 17, 2018
• Study Start: January 15, 2018
• Primary Completion: May 30, 2018
• Study Completion: May 30, 2018
• Last Updated: June 3, 2021
• Results First Posted: July 29, 2019

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (1)