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

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT04526210

Collaborator

(none)

Enrollment

Location

Arms

6.9

Actual Duration (Months)

7.8

Patients Per Site Per Month

Study Details

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

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 :

Oct 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 Names: 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 Names: Wellbutrin SR 150

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: 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 Names:

Wellbutrin SR 150

Outcome Measures

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) Of Bupropion With And Without The Coadministration Of ALXN1840 [Baseline, 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 [Baseline, 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 [Baseline, up to 336 hours post-dose]

Secondary Outcome Measures

Cmax Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 [Baseline, up to 336 hours post-dose]
AUCt Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 [Baseline, up to 336 hours post-dose]
AUCinf Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 [Baseline, up to 336 hours post-dose]
Cmax Of Molybdenum With Coadministration Of Bupropion [Baseline, up to 336 hours post-dose]
AUCt Of Molybdenum With Coadministration Of Bupropion [Baseline, up to 336 hours post-dose]
AUCinf Of Molybdenum With Coadministration Of Bupropion [Baseline, up to 336 hours post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.