Wilson DiseasePhase 1NCT04526210

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

A Phase 1 study testing ALXN1840 and Bupropion Hydrochloride in people with Wilson Disease, run by Alexion Pharmaceuticals, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Wilson Disease
What is being tested?: ALXN1840 and Bupropion Hydrochloride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 54 participants
Where: 1 siteUnited States
Study dates: 21 Oct 2020to 28 May 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Trial Site
Austin, Texas, 78744

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Wilson Disease
Being tested: ALXN1840, Bupropion Hydrochloride
Keywords: Cytochrome P450, Healthy, ALXN1840
Medical subject headings: Hepatolenticular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ALXN1840Drug
Also called WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline
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.
Bupropion HydrochlorideDrug
Also called Wellbutrin SR 150
Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).

Study groups in NCT04526210
Study group	Role	What they receive
Treatment A	Experimental	Participants will receive bupropion. Receives: Drug: Bupropion Hydrochloride
Treatment B	Experimental	Participants will receive bupropion with ALXN1840. Receives: Drug: ALXN1840; Drug: Bupropion Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840
Measured: 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
Measured: 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
Measured: Pre-dose (Day 1) up to 336 hours post-dose

Secondary outcomes (7)

Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840
Measured: Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840
Measured: Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 up to Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Oct 202028 May 2021

First posted25 Aug 2020
Study start21 Oct 2020
Primary completion28 May 2021
Study completion28 May 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Wilson DiseaseStudies of the same condition, open and under way.
More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 54 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04526210
Sponsor's protocol ID: ALXN1840-HV-103
Status last verified: Oct 2022
First submitted: 19 Aug 2020
Last updated: 31 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04526210
Acronym / sponsor ID: ALXN1840-HV-103
Conditions: Wilson Disease
Keywords: Cytochrome P450, Healthy, ALXN1840
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 54 participants (actual)
Lead sponsor: Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 21 Oct 2020 (actual)
Primary completion: 28 May 2021 (actual)
Study completion: 28 May 2021 (actual)
First posted: 25 Aug 2020 (actual)
Results: Posted 31 Aug 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment A	Experimental	Drug: Bupropion HydrochlorideParticipants will receive bupropion.
Treatment B	Experimental	Drug: ALXN1840, Drug: Bupropion HydrochlorideParticipants will receive bupropion with ALXN1840.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ALXN1840Also: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate cholineALXN1840 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.	Drug	Treatment B
Bupropion HydrochlorideAlso: Wellbutrin SR 150Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).	Drug	Treatment A, Treatment B

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840
Time frame: 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
Time frame: 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
Time frame: Pre-dose (Day 1) up to 336 hours post-dose

7 secondary outcomes

Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
Cmax of Plasma Total Molybdenum With Coadministration of Bupropion
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Plasma Total Molybdenum With Coadministration of Bupropion
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Plasma Total Molybdenum With Coadministration of Bupropion
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Day 1 up to Day 15

Results and safety

Results posted to the registry on 31 Aug 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Sequence A-B	27	17
Treatment Sequence B-A	27	20

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840

Time frame: Pre-dose (Day 1) up to 336 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: nanograms (ng)/milliliter (mL)

Measure	Treatment A: Bupropion HCl n = 37	Treatment B: Bupropion HCl + ALXN1840 n = 36
Value	98.64 (31.6)	98.02 (27.9)

Treatment A: Bupropion HCl vs Treatment B: Bupropion HCl + ALXN1840: Geometric least square (LS) mean ratio: 0.980 (90% CI 0.9415 to 1.0205)

Population analysed: Pharmacokinetic (PK) analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Primary outcome: 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: Pre-dose (Day 1) up to 336 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: hours*ng/mL

Measure	Treatment A: Bupropion HCl n = 37	Treatment B: Bupropion HCl + ALXN1840 n = 36
Value	1021 (33.4)	1010 (31.6)

Treatment A: Bupropion HCl vs Treatment B: Bupropion HCl + ALXN1840: Geometric LS mean ratio: 0.978 (90% CI 0.9344 to 1.0244)

Population analysed: PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Primary outcome: 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: Pre-dose (Day 1) up to 336 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: hours*ng/mL

Measure	Treatment A: Bupropion HCl n = 37	Treatment B: Bupropion HCl + ALXN1840 n = 36
Value	1049 (32.9)	1039 (31.3)

Treatment A: Bupropion HCl vs Treatment B: Bupropion HCl + ALXN1840: Geometric LS mean ratio: 0.981 (90% CI 0.9368 to 1.0269)

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 up to Day 15. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A: Bupropion HCl	0 of 50 (0%)	8 of 50 (16%)	0 of 50
Treatment B: Bupropion HCl + ALXN1840	0 of 50 (0%)	11 of 50 (22%)	0 of 50

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ALXN1840 and Bupropion Hydrochloride in people with Wilson Disease, run by Alexion Pharmaceuticals, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840 (time frame: Pre-dose (Day 1) up to 336 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04526210.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.