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

NCT04526197 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ALXN1840-HV-105
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Wilson Disease

Keywords

Cytochrome P450; Healthy; ALXN1840; Celecoxib; CYP2C9

Outcome Measures

Primary Outcomes (3)

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

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

  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 Celecoxib With And Without The Coadministration Of ALXN1840

  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).

  Baseline, up to 336 hours post-dose

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

  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.

  Baseline, up to 336 hours post-dose

Secondary Outcomes (3)

• Cmax Of Molybdenum With Coadministration Of Celecoxib

  Baseline, up to 336 hours post-dose

• AUCt Of Molybdenum With Coadministration Of Celecoxib

  Baseline, up to 336 hours post-dose

• AUCinf Of Molybdenum With Coadministration Of Celecoxib

  Baseline, up to 336 hours post-dose

Study Arms (2)

Treatment Sequence A-B

EXPERIMENTAL

Participants received 1 treatment during each study period in the following sequence: * Treatment A: Celecoxib. * Treatment B: Celecoxib plus ALXN1840.

Drug: ALXN1840; Drug: Celecoxib

Treatment Sequence B-A

EXPERIMENTAL

Participants received 1 treatment during each study period in the following sequence: * Treatment B: Celecoxib plus ALXN1840. * Treatment A: Celecoxib.

Drug: ALXN1840; Drug: Celecoxib

Interventions

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.

Also known as: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline

Treatment Sequence A-B; Treatment Sequence B-A

Celecoxib DRUG

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

Treatment Sequence A-B; Treatment Sequence B-A

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (1)

Clinical Trial Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

tetrathiomolybdate; Celecoxib

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 25, 2020
• Study Start: July 7, 2020
• Primary Completion: November 3, 2020
• Study Completion: November 3, 2020
• Last Updated: August 21, 2023
• Results First Posted: August 21, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)