Study of ALXN1840 on the Metabolism of a CYP2B6 Substrate in Healthy Participants

A Phase 1, Randomized, 2-Period, 2-Sequence, Cross-over Study to Determine the Effect of ALXN1840 on the Metabolism of a CYP2B6 Substrate in Healthy Participants

This is a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of bupropion, a sensitive cytochrome P450 2B6 (CYP2B6) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 will be determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of bupropion.

Study Overview

• Status: Completed
• Conditions: Wilson Disease
• Intervention / Treatment: Drug: Bupropion Hydrochloride; Drug: ALXN1840

Detailed Description

The study is being conducted as a randomized, 2-period, 2-sequence, cross-over study to determine the effect of a single dose of ALXN1840 (perpetrator) on the single-dose bupropion (victim) kinetics in healthy male and female participants.

The study has a Screening Period (Day -28 to Day -2), two 11-day study periods (Day 1 to Day 11) with a minimum of 14 days between doses of bupropion, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants will report to the clinical research unit on the day prior (Day -1) to both dosing periods. All participants will receive 1 treatment in each study period; treatment order will be defined based on randomization: Treatments A and B.

The time between dosing bupropion alone or in combination with ALXN1840 in each treatment sequence will be a minimum of 14 days.

The PK profile of ALXN1840 and bupropion will be determined by blood sampling following single dose administration.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adequate venous access in the left or right arm to allow the collection of blood samples.
• Body weight ≥ 45 to ≤ 100 kilograms (kg) and body mass index within the range of 18 to < 30 kg/meter squared.
• Willing and able to follow protocol-specified contraception requirements.
• Capable of giving signed informed consent.

Exclusion Criteria:

• History or presence of/significant medical history.
• Clinically significant multiple or severe allergies.
• Lymphoma, leukemia, or any malignancy within 5 years.
• Breast cancer within the past 10 years.
• Serum creatinine > upper limit of normal (ULN) of the reference range.
• Alanine aminotransferase, aspartate aminotransferase, or total bilirubin > ULN.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QTc > 450 milliseconds (msec) for male participants or > 470 msec for female participants.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Participants will receive bupropion.	Drug: Bupropion Hydrochloride; Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).; Other Names: Wellbutrin SR 150
Experimental: Treatment B; Participants will receive bupropion with ALXN1840.	Drug: Bupropion Hydrochloride; Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).; Other Names: Wellbutrin SR 150; Drug: ALXN1840; ALXN1840 will be administered orally as a single dose as 4 x 15 mg enteric-coated tablets with 240 milliliters of water (fasting), for a total dose of 60 mg.; Other Names: Tiomolibdate choline; WTX101; Bis-choline tetrathiomolybdate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840	Pre-dose (Day 1) up to 336 hours post-dose
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) of Bupropion With and Without the Coadministration of ALXN1840	Pre-dose (Day 1) up to 336 hours post-dose
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUCinf) of Bupropion With and Without the Coadministration of ALXN1840	Pre-dose (Day 1) up to 336 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
Cmax of Plasma Total Molybdenum With Coadministration of Bupropion	Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only.	Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Plasma Total Molybdenum With Coadministration of Bupropion	Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only.	Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Plasma Total Molybdenum With Coadministration of Bupropion	Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only.	Pre-dose (Day 1) up to 336 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with the study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A TEAE was defined as any AE that began or worsened on or after the first dose of treatment until the end of study (EOS) or early termination (ET). An AE that occurred during the washout period between drugs was considered treatment emergent to the last drug given. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Day 1 up to Day 15

Collaborators and Investigators

• Sponsor: Alexion

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2020
• Primary Completion (Actual): May 28, 2021
• Study Completion (Actual): May 28, 2021

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Healthy; Cytochrome P450; ALXN1840
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Metal Metabolism, Inborn Errors; Hepatolenticular Degeneration; Physiological Effects of Drugs; Neurotransmitter Agents; 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; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Chelating Agents; Sequestering Agents; Nootropic Agents; Lipotropic Agents; Bupropion; Choline; Tetrathiomolybdate
• Other Study ID Numbers: ALXN1840-HV-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No