Clinical trial NCT03918239: A Study to Determine the Bioavailability of Lanadelumab (SHP643) Administered Subcutaneously With the Prefilled Syringe and the Autoinjector in Healthy Adult Volunteer Participants.
Official title: A Randomized, Open-label, Single-dose, Parallel-arm, Single-center, Phase 1 Study to Determine the Bioavailability of Lanadelumab Administered Subcutaneously With the Prefilled Syringe and the Autoinjector in Healthy Adult Volunteer Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-04-17
Enrollment: 190
Sex: ALL
Minimum age (years): 18
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 is to evaluate bioavailability of lanadelumab (SHP643) following a single, 2 milliliter (mL) subcutaneous (SC) dose of 300 milligrams (mg) delivered by prefilled syringe (PFS) or auto injector (AI) in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* An understanding, ability, and willingness to fully comply with study procedures and restrictions.
* Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
* 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.
* 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.
* Must be considered "healthy", per the investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.
* Body mass index between 18.5-33 kilogram per square meter (kg/m\^2), inclusive, with a body weight greater than or equal to (\>=) 45 kilogram (kg) (99 pounds \[lbs\]). This inclusion criterion will only be assessed at the screening visit and on Day -1.
* Willing and able to consume standardized meals during the confinement period of the study.
* All participants will be required to consume the identical meals on study days when serial PK blood samples are collected

Exclusion Criteria:

* Per the investigator, a 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.
* Per the investigator, a current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to complete the study, or any condition that present's undue risk from the investigational product or procedures.
* Known or suspected intolerance or hypersensitivity to the investigational product, closelyrelated 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 (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 \<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) \>139 millimeters of mercury (mmHg) or \<89 mmHg, and diastolic BP \>89 mmHg or \<49 mmHg.
* Twelve-lead ECG values demonstrating QTcF \>450 milliseconds (msec) (males) or \>470 msec (females) at the screening visit or Day -1. If QTcF exceeds 450 msec (males) or 470 msec (females), the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participants eligibility.
* Positive screen for drugs of abuse and/or disallowed drugs (i.e. amphetamines, benzodiazepines, barbiturates, cocaine, opiates, phencyclidine) at screening, or drugs of abuse or alcohol on Day -1. This screen will include marijuana.
* Male participants who consume more than 21 units of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day. One alcohol unit=1 beer or 1 wine (5 ounces \[oz) per 150 milliliter \[mL\]) or 1 liquor (1.5 oz/40 mL) or 0.75 oz alcohol.
* Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.
* Use of tobacco in any form (e.g. smoking or chewing) or other nicotine-containing products in any form (e.g. 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 participants who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6 oz (180 ml) cup of coffee, two 12 oz (360 ml) cans of cola, one 12 oz cup of tea, and three 1 oz (85 g) 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 stable hormonal replacement therapy or hormonal contraceptives). Current use is defined as use within 14 days of the dose of investigational product. (Prior and Concomitant Treatment) for a list of permitted medications.
* 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: Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose
measure: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
measure: Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
measure: Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
measure: Terminal Half-Life (T1/2) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
measure: Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
measure: Apparent Volume of Distribution Associated With the Terminal Slope Following Extravascular Administration Divided by the Fraction of Dose Absorbed (Vdz/F) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
measure: Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma
timeFrame: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
measure: Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points
timeFrame: Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET])
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, LLC
state: Florida
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: