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Study of Lanadelumab in Healthy Japanese and Matched Caucasian Adult Subjects

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ClinicalTrials.gov Identifier: NCT03401671
Recruitment Status : Completed
First Posted : January 17, 2018
Last Update Posted : May 31, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

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
Healthy Volunteers Drug: Lanadelumab Phase 1

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Study Type : Interventional  (Clinical Trial)
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 : January 15, 2018
Actual Primary Completion Date : May 30, 2018
Actual Study Completion Date : May 30, 2018

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 Name: 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 Name: SHP643




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 hours (h) post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Cmax is the maximum observed plasma concentration of lanadelumab

  2. Time to Reach Maximum Observed Drug Concentration in Plasma (Tmax) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.

  3. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    AUC0-last is the area under the concentration-time curve from time zero to the last quantifiable concentration of lanadelumab.

  4. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    AUC0-infinity is the area under the concentration time curve from time zero extrapolated to infinity.

  5. Terminal Elimination Rate Constant (Lambda z) for Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Lambda z is the terminal elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  6. Terminal Half-life (t12) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    t1/2 is the time required for the plasma concentration of the drug to reach half of its original value.

  7. Apparent Clearance (CL/F) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    CL/F is defined as the rate at which a drug is removed from the body.

  8. Apparent Volume of Distribution (Vdz/F) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

  9. Body-weight Adjusted Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) in Plasma of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Body-weight adjusted AUC0-last in plasma will be measured.

  10. Body-weight Adjusted Maximum Observed Plasma Concentration (Cmax) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Body-weight adjusted Cmax in plasma will be measured.

  11. Body-weight Adjusted Apparent Clearance (CL/F) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Body-weight adjusted CL/F will be measured.

  12. Body-weight Adjusted Apparent Volume of Distribution (Vdz/F) of Lanadelumab [ Time Frame: Pre-dose, 8, 24, 48, 72, 96 h post-dose, Days 7, 14, 21, 28, 42, 56, 84, 112 ]
    Body-weight adjusted Vdz/F will be measured.


Secondary Outcome Measures :
  1. Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Based on Severity, Seriousness and Causality [ Time Frame: From start of study drug administration up to End of Study / Early Discontinuation (Day 112) ]
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject 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 subject; Severe: An AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

  2. Number of Subjects With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event [ Time Frame: Day -1 up to End of Study / Early Discontinuation (Day 112) ]
    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.

  3. Number of Subjects With Clinically Significant Change in Vital Signs Reported as an Adverse Event [ Time Frame: Pre-dose up to End of Study / Early Discontinuation (Day 112) ]
    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 Subjects With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event [ Time Frame: Pre-dose up to End of Study / Early Discontinuation (Day 112) ]
    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 Subjects With Clinically Significant Findings in Physical Examination Reported as an Adverse Event [ Time Frame: Day -1 up to End of Study / Early Discontinuation (Day 112) ]
    Complete physical examinations will be carried out which include review of the following body systems: general appearance, skin, head, eyes, ears, nose, and throat, spine, neck or thyroid, musculoskeletal, respiratory, cardiovascular, neurological and abdomen (including liver and kidneys). Any changes from the baseline in physical examination findings that are deemed clinically significant by the investigator are to be recorded as an AE.

  6. Number of Subjects who Develop Antidrug Antibodies to Lanadelumab [ Time Frame: Day 1 pre-dose up to End of Study / Early Discontinuation (Day 112) ]
    Plasma samples will be analyzed for presence of antidrug antibodies to lanadelumab. Subjects who show positive results for lanadelumab antibodies will be reported.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401671


Locations
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United States, California
WCCT Global, Inc.
Cypress, California, United States, 90630
Sponsors and Collaborators
Shire
Investigators
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Study Director: Shire Study Physician Shire

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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03401671     History of Changes
Other Study ID Numbers: SHP643-101
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shire:
Lanadelumab