Clinical trial NCT04503603: A Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Participants
Official title: A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2020-08-07
Enrollment: 12
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study to evaluate the safety, tolerability and pharmacokinetics (PK) of lanadelumab administered by Intravenous (IV) infusion in healthy adult volunteers.

Detailed description: A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Subjects

Eligibility criteria: Inclusion Criteria:

* Healthy, adult, male or female, 19-55 years of age, inclusive, at screening.
* Continuous non-smoker who has not used nicotine-containing products for at least 30 days prior to the first dosing and throughout the study, based on participant self-reporting.
* Body mass index (BMI) greater than or equal to (\>=) 18.0 and less than or equal to (\<=) 32.0 kilogram per square meter (kg/m\^2) at screening.
* Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), per the investigator.
* 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.
* Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.

Exclusion Criteria:

* Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
* History or presence of clinically significant medical or psychiatric condition or disease per the investigator.
* History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study, per the investigator.
* History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing per the investigator.
* History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
* History or presence 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 clinically significant clinical or laboratory assessments per the investigator.
* Female participants with a positive pregnancy test or lactating.
* Positive urine drug or alcohol results at screening.
* Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
* Supine blood pressure is less than 90/40 millimetre of mercury (mmHg) or greater than 140/90 mmHg at screening.
* Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
* Orthostatic vital sign results with a decrease in systolic greater than (\>) 20 mmHg or decrease in diastolic \> 10 mmHg and increase in pulse of \> 20 beats per minute.
* QTcF interval is \> 450 milliseconds (msec) (males) or \> 470 msec (females) or ECG findings are deemed abnormal with clinical significance at screening per the investigator.
* Estimated creatinine clearance less than (\<) 80 milliliters per minute (mL/min) at screening.
* Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration. After randomization/dosing, a nonsteroidal anti-inflammatory drug may be administered at the discretion of the investigator. Hormone replacement therapy will also be allowed if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration.
* Has been on a diet incompatible with the on-study diet, per the investigator, within the 30 days prior to the first dosing and throughout the study.
* Donation of blood or significant blood loss within 56 days prior to the first dosing.
* Plasma donation within 7 days prior to the first dosing.
* Participation in another clinical study within 30 days or 5 half-lives prior to the first dosing. The 30-day window or 5 half-lives will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the first dose of study treatment up to the end of study (Day 112)
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
timeFrame: From the first dose of study treatment up to the end of study (Day 112)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: From the first dose of study treatment up to the end of study (Day 112)
measure: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
timeFrame: From the first dose of study treatment up to the end of study (Day 112)
measure: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration for Lanadelumab
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: AUC0-inf: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity for Lanadelumab
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: Cmax1: Maximum Observed Plasma Concentration Following the First IV Dose for Lanadelumab
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: Cmax2: Maximum Observed Plasma Concentration Following the Second IV Dose for Lanadelumab
timeFrame: Pre-dose (Day 4) up to 2592 hours post-dose
measure: Tmax1: Minimum Observed Time to Reach the First Cmax1 for Lanadelumab
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: Tmax2: Minimum Observed Time to Reach the Second Cmax2 for Lanadelumab
timeFrame: Pre-dose (Day 4) up to 2592 hours post-dose
measure: Terminal Half-Life (T1/2) of Lanadelumab in Plasma
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: Clearance (CL) of Lanadelumab in Plasma
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: Vss: Volume of Distribution at Steady State in Plasma for Lanadelumab
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
measure: First Order Elimination Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of Lanadelumab
timeFrame: Pre-dose (Day 1) up to 2664 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Takeda Development Center Americas, Inc.
name: Study Director
role: STUDY_DIRECTOR
References: