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

NCT04526210 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ALXN1840-HV-103
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Wilson Disease

Keywords

Cytochrome P450; Healthy; ALXN1840

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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

  Pre-dose (Day 1) up to 336 hours post-dose

• AUCt of Plasma Total Molybdenum With Coadministration of Bupropion

  Pre-dose (Day 1) up to 336 hours post-dose

Study Arms (2)

Treatment A

EXPERIMENTAL

Participants will receive bupropion.

Drug: Bupropion Hydrochloride

Treatment B

EXPERIMENTAL

Participants will receive bupropion with ALXN1840.

Drug: ALXN1840; Drug: Bupropion Hydrochloride

Interventions

ALXN1840 DRUG

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.

Also known as: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline

Treatment B

Bupropion Hydrochloride DRUG

Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).

Also known as: Wellbutrin SR 150

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (1)

Clinical Trial Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

tetrathiomolybdate; Bupropion

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

+1 855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 25, 2020
• Study Start: October 21, 2020
• Primary Completion: May 28, 2021
• Study Completion: May 28, 2021
• Last Updated: August 31, 2023
• Results First Posted: August 31, 2023

Record last verified: 2022-10

Locations

US (1)