Skip to main content
OpenTrials
Completed

NCT Number: NCT04526197

Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.

This was a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of celecoxib, a sensitive cytochrome P450 2C9 (CYP2C9) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 were determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of celecoxib.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Wilson Disease Basal Ganglia Diseases Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Hepatolenticular Degeneration Heredodegenerative Disorders, Nervous System Liver Diseases Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Movement Disorders Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Trial Site

Austin, Texas, 78744, United States

About this study

The study was 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 celecoxib (victim) kinetics in healthy male and female participants.

The study had 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 celecoxib, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants only reported to the clinical research unit (CRU) on the day prior to the first dose because they were kept in the CRU during the wash-out period due to coronavirus disease 2019.

All participants received a single dose of celecoxib alone (Treatment A) and celecoxib coadministered with ALXN1840 (Treatment B) during the study, 1 in each treatment period. Based on randomization, participants were administered either Treatments A-B or Treatments B-A in each study period.

The PK profile of ALXN1840 and celecoxib was determined by blood sampling following single-dose administration. In addition to PK sampling, safety and tolerability were assessed by monitoring adverse events, vital signs, 12-lead electrocardiograms, physical examinations, and laboratory parameters.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adequate venous access in the left or right arm to allow the collection of blood samples.
  • Bodyweight ≥ 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.

Treatment and study plan

ALXN1840

Drug

ALXN1840 was administered orally as a single dose as 4 x 15 milligram (mg) enteric-coated tablets with 240 milliliters (mL) of water (fasting), for a total dose of 60 mg.

Other names: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline

Celecoxib

Drug

Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting).

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840

    Time frame: Baseline, up to 336 hours post-dose

    Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).

  2. Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) Of Celecoxib With And Without The Coadministration Of ALXN1840

    Time frame: Baseline, up to 336 hours post-dose

    Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) is reported as hours•ng/mL (h•ng/mL).

  3. Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) Of Celecoxib With And Without The Coadministration Of ALXN1840

    Time frame: Baseline, up to 336 hours post-dose

    Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) is reported as h•ng/mL.

Secondary outcomes

  1. Cmax Of Molybdenum With Coadministration Of Celecoxib

    Time frame: Baseline, up to 336 hours post-dose

    Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and plasma ultrafiltrate (PUF) molybdenum. Cmax is reported as ng/mL.

  2. AUCt Of Molybdenum With Coadministration Of Celecoxib

    Time frame: Baseline, up to 336 hours post-dose

    Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and PUF molybdenum. AUCt is reported as h•ng/mL.

  3. AUCinf Of Molybdenum With Coadministration Of Celecoxib

    Time frame: Baseline, up to 336 hours post-dose

    Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and PUF molybdenum. AUCinf is reported as h•ng/mL.

Sponsors and collaborators

Lead sponsor

Alexion Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 1, Randomized, 2-Period, 2-Sequence, Cross-over Study to Determine the Effect of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Aug 25, 2020
Registry last updated
Aug 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.