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

Wilson Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04526210
• Other study ID #: ALXN1840-HV-103
• Status: Completed
• Phase: Phase 1
• Start date: October 21, 2020
• Est. completion date: May 28, 2021

Study information

• Verified date: October 2022
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: May 28, 2021
• Est. primary completion date: May 28, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Wilson Disease

Intervention

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

Locations

Country	Name	City	State
United States	Clinical Trial Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Alexion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
Primary	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
Primary	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	Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
Secondary	AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
Secondary	AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840		Pre-dose (Day 1) up to 336 hours post-dose
Secondary	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.	Pre-dose (Day 1) up to 336 hours post-dose
Secondary	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.	Pre-dose (Day 1) up to 336 hours post-dose
Secondary	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.	Pre-dose (Day 1) up to 336 hours post-dose
Secondary	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.	Day 1 up to Day 15