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

• ClinicalTrials.gov Identifier: NCT04526210
• Recruitment Status: Completed
• First Posted: August 25, 2020
• Last Update Posted: July 22, 2021
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Wilson Disease	Drug: ALXN1840; Drug: Bupropion Hydrochloride	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 21, 2020
• Actual Primary Completion Date: May 19, 2021
• Actual Study Completion Date: May 19, 2021

Arms and Interventions

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 Name: Wellbutrin SR 150
Experimental: Treatment B; Participants will receive bupropion with ALXN1840.	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: WTX101; Bis-choline tetrathiomolybdate; Tiomolibdate choline; 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 Name: Wellbutrin SR 150

Outcome Measures

Primary Outcome Measures :

1. Maximum Observed Plasma Concentration (Cmax) Of Bupropion With And Without The Coadministration Of ALXN1840 [ Time Frame: Baseline, up to 336 hours post-dose ]
2. 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 [ Time Frame: Baseline, up to 336 hours post-dose ]
3. Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) Of Bupropion With And Without The Coadministration Of ALXN1840 [ Time Frame: Baseline, up to 336 hours post-dose ]

Secondary Outcome Measures :

1. Cmax Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 [ Time Frame: Baseline, up to 336 hours post-dose ]
2. AUCt Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 [ Time Frame: Baseline, up to 336 hours post-dose ]
3. AUCinf Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 [ Time Frame: Baseline, up to 336 hours post-dose ]
4. Cmax Of Molybdenum With Coadministration Of Bupropion [ Time Frame: Baseline, up to 336 hours post-dose ]
5. AUCt Of Molybdenum With Coadministration Of Bupropion [ Time Frame: Baseline, up to 336 hours post-dose ]
6. AUCinf Of Molybdenum With Coadministration Of Bupropion [ Time Frame: Baseline, up to 336 hours post-dose ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Texas

Clinical Trial Site

Austin, Texas, United States, 78744

Sponsors and Collaborators

Alexion Pharmaceuticals

More Information

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04526210
• Other Study ID Numbers: ALXN1840-HV-103
• First Posted: August 25, 2020
• Last Update Posted: July 22, 2021
• Last Verified: July 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion Pharmaceuticals:

Cytochrome P450; Healthy; ALXN1840

Additional relevant MeSH terms:

Hepatolenticular Degeneration; 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; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Tetrathiomolybdate; Choline; Bupropion; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Cytochrome P-450 CYP2D6 Inhibitors