A Study to Determine the Bioavailability of Lanadelumab (SHP643) Administered Subcutaneously With the Prefilled Syringe and the Autoinjector in Healthy Adult Volunteer Participants.

NCT03918239 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SHP643-102
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (8)

• Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma

  AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose

• Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma

  AUC(0-infinity) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

• Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma

  Cmax is the maximum observed plasma concentration of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

• Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma

  Tmax of of SHP643 in plasma was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

• Terminal Half-Life (T1/2) of SHP643 in Plasma

  t1/2 of of SHP643 in plasma was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

• Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma

  CL/F of of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

• 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

  Vdz/F of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

• Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma

  Lambda z of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

  Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose

Secondary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])

• Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points

  Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET])

Study Arms (2)

SHP643 Prefilled Syringe (PFS)

EXPERIMENTAL

Participants will receive 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house period (Day 1 to Day 5).

Drug: SHP643

SHP643 Autoinjector (AI)

EXPERIMENTAL

Participants will receive 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house period (Day 1 to Day 5).

Drug: SHP643

Interventions

SHP643 DRUG

Participants will receive injection of SHP643.

Also known as: DX-2930 (formerly), Lanadelumab

SHP643 Autoinjector (AI); SHP643 Prefilled Syringe (PFS)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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

You may not qualify if:

• 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.
• Have used an investigational product (if elimination half-life is \<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) \>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.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Interventions

lanadelumab; rhoA GTP-Binding Protein

Intervention Hierarchy (Ancestors)

rho GTP-Binding Proteins; Monomeric GTP-Binding Proteins; GTP-Binding Proteins; GTP Phosphohydrolases; Acid Anhydride Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Intracellular Signaling Peptides and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.com

+1 866-842-5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 17, 2019
• Study Start: May 14, 2019
• Primary Completion: November 13, 2019
• Study Completion: November 13, 2019
• Last Updated: December 8, 2020
• Results First Posted: December 8, 2020

Record last verified: 2020-11

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)