Study of Oral ALXN1840 at 2 Dose Strengths in Healthy Adults

A Phase 1, Randomized, Open-Label, 2-Way Crossover Study to Assess the Single-Dose Pharmacokinetics of ALXN1840 Enteric-Coated Tablets at 2 Dose Strengths in Healthy Adult Subjects

To assess the relative bioavailability of ALXN1840 administered orally as a single enteric-coated (EC) tablet (reference, Treatment A) versus three EC tablets (test, Treatment B).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN1840

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE11YR
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body weight ≤ 100 kilograms (kg) and body mass index within the range 18-25 kg/meter squared, inclusive, at Screening.
• Negative serum pregnancy test at Screening and Day -1 for all women of childbearing potential.
• Willing to adhere to contraception requirements.
• Satisfactory medical assessment with no clinically significant or relevant abnormalities.

Exclusion Criteria:

• Current or recurrent/chronic disease
• Positive test for hepatitis B surface antigen or human immunodeficiency virus antibody at Screening.
• Acute or chronic hepatitis C virus infection.
• History of hypersensitivity to ALXN1840 or its excipients or any significant allergic reaction.
• Use of prescription medications (excluding oral contraceptives) within 14 days prior to dosing on Day 1, except with prior approval of the Sponsor.
• Participation (that is, last protocol-required study visit) in a clinical study within 90 days before initiation of dosing on Day 1.
• Serum ceruloplasmin value outside of the normal range at Screening
• Female participants who were breastfeeding.
• Prior exposure to ALXN1840.
• Major surgery or hospitalization within 90 days prior to dosing on Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1 (AB); Participants received ALXN1840 once in each Period as a single oral dose under fasted conditions as follows: Period 1: ALXN1840 as a single EC tablet (Treatment A, reference). Period 2: ALXN1840 as three EC tablets (Treatment B, test). Participants were discharged following the 240-hour post-dose procedures (approximately 10 days after dosing in each period) unless it was medically necessary to extend the confinement. There was a washout period of at least 14 days between each ALXN1840 dosing.	Drug: ALXN1840; Participants received ALXN1840 at Hour 0 on Day 1 of the dosing period.; Other Names: WTX101 (formerly); Bis-choline Tetrathiomolybdate; Tiomolibdic Acid
Experimental: Sequence 2 (BA); Participants received ALXN1840 once in each Period as a single oral dose under fasted conditions as follows: Period 1: ALXN1840 as three EC tablets (Treatment B, test). Period 2: ALXN1840 as a single EC tablet (Treatment A, reference). Participants were discharged following the 240-hour post-dose procedures (approximately 10 days after dosing in each period) unless it was medically necessary to extend the confinement. There was a washout period of at least 14 days between each ALXN1840 dosing.	Drug: ALXN1840; Participants received ALXN1840 at Hour 0 on Day 1 of the dosing period.; Other Names: WTX101 (formerly); Bis-choline Tetrathiomolybdate; Tiomolibdic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed (Plasma) Concentration (Cmax) of Total Molybdenum	The pharmacokinetic (PK) data of plasma total molybdenum were analyzed in the scope of this study as a surrogate measure for ALXN1840. Whole blood samples were collected for the measurement of plasma concentrations of total molybdenum via inductively coupled plasma-mass spectroscopy (ICP-MS).	Up to 240 hours postdose
Area Under The Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) of Total Molybdenum	The PK data of plasma total molybdenum were analyzed in the scope of this study as a surrogate measure for ALXN1840. Whole blood samples were collected for the measurement of plasma concentrations of total molybdenum via ICP-MS.	Up to 240 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Treatment-Emergent Adverse Event (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was an AE that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. A related TEAE was defined as having a reasonable possibility the study intervention caused the AE as assessed by the investigator. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Baseline up to Day 43

Collaborators and Investigators

• Sponsor: Alexion

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2019
• Primary Completion (Actual): October 9, 2019
• Study Completion (Actual): October 9, 2019

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Pharmacodynamics; ALXN1840; Enteric-coated tablet
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Gastrointestinal Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Hypolipidemic Agents; Lipid Regulating Agents; Chelating Agents; Sequestering Agents; Nootropic Agents; Lipotropic Agents; Choline; Tetrathiomolybdate
• Other Study ID Numbers: ALXN1840-HV-104; 2019-000516-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes