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

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

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.

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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


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




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 ]


Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04526210


Locations
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United States, Texas
Clinical Trial Site
Austin, Texas, United States, 78744
Sponsors and Collaborators
Alexion Pharmaceuticals
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04526210    
Other Study ID Numbers: ALXN1840-HV-103
First Posted: August 25, 2020    Key Record Dates
Last Update Posted: July 22, 2021
Last Verified: July 2021

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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:
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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