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

Primary Purpose

Wilson Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ALXN1840

Bupropion Hydrochloride

About this trial

This is an interventional treatment trial for Wilson Disease focused on measuring Cytochrome P450, Healthy, ALXN1840

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Clinical Trial Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Treatment A

Treatment B

Arm Description

Participants will receive bupropion.

Participants will receive bupropion with ALXN1840.

Outcomes

Primary Outcome Measures

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

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

Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUCinf) of Bupropion With and Without the Coadministration of ALXN1840

Secondary Outcome Measures

Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840

AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840

AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840

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.

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.

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.

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.

Full Information

NCT ID

NCT04526210

First Posted

August 19, 2020

Last Updated

October 17, 2022

Sponsor

Alexion

1. Study Identification

Unique Protocol Identification Number

NCT04526210

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

October 21, 2020 (Actual)

Primary Completion Date

May 28, 2021 (Actual)

Study Completion Date

May 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alexion

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Wilson Disease

Keywords

Cytochrome P450, Healthy, ALXN1840

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment A

Arm Type

Experimental

Arm Description

Participants will receive bupropion.

Arm Title

Treatment B

Arm Type

Experimental

Arm Description

Participants will receive bupropion with ALXN1840.

Intervention Type

Drug

Intervention Name(s)

ALXN1840

Other Intervention Name(s)

WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Bupropion Hydrochloride

Other Intervention Name(s)

Wellbutrin SR 150

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame