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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Sequence A-B | Experimental | Participants received 1 treatment during each study period in the following sequence:
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| Treatment Sequence B-A | Experimental | Participants received 1 treatment during each study period in the following sequence:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax Of Molybdenum With Coadministration Of Celecoxib | 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. | Baseline, up to 336 hours post-dose |
| AUCt Of Molybdenum With Coadministration Of Celecoxib |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Austin | Texas | 78744 | United States |
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Participants were randomized to 1 of 2 treatment sequences (A-B) or (B-A) in a crossover study design during 2 dosing periods. Participants were scheduled to receive either treatment A or B on Day 1 of each dosing period. There was a washout of at least 14 days between the dosing periods.
A total of 70 potential participants were screened for this study, and 36 participants were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence A-B | All participants were randomized to 1 of 2 treatment sequences (A-B or B-A) and received 1 treatment in each study period; treatment order was defined based on randomization:
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| FG001 | Treatment Sequence B-A | All participants were randomized to 1 of 2 treatment sequences (A-B or B-A) and received 1 treatment in each study period; treatment order was defined based on randomization:
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| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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All participants who received at least 1 dose of study drug during treatment period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Sequence A-B | Participants received 1 treatment during each study period in the following sequence:
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| BG001 | Treatment Sequence B-A |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data. | Posted | Mean | Standard Deviation | ng/mL | Baseline, up to 336 hours post-dose |
|
Day 1 through 15 (± 2) days after final dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A | Participants who received celecoxib. | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals, Inc. | Alexion Pharmaceuticals, Inc. | 855-752-2356 | clinicaltrials@alexion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 28, 2020 | Apr 1, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 4, 2020 | Apr 1, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006527 | Hepatolenticular Degeneration |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| C020809 | tetrathiomolybdate |
| D000068579 | Celecoxib |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.
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| Celecoxib | Drug | Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting). |
|
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. |
| Baseline, up to 336 hours post-dose |
| AUCinf Of Molybdenum With Coadministration Of Celecoxib | 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. | Baseline, up to 336 hours post-dose |
| COMPLETED |
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| NOT COMPLETED |
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Participants received 1 treatment during each study period in the following sequence:
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Height | Mean | Standard Deviation | Centimeters |
|
| Weight | Mean | Standard Deviation | Kilograms |
|
| Body Mass Index | Mean | Standard Deviation | Kilograms/squared meter |
|
|
|
|
| Primary | 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). | Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data. | Posted | Mean | Standard Deviation | h•ng/mL | Baseline, up to 336 hours post-dose |
|
|
|
|
| Primary | 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. | Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data. | Posted | Mean | Standard Deviation | h•ng/mL | Baseline, up to 336 hours post-dose |
|
|
|
|
| Secondary | Cmax Of Molybdenum With Coadministration Of Celecoxib | 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. | Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data. | Posted | Mean | Standard Deviation | ng/mL | Baseline, up to 336 hours post-dose |
|
|
|
| Secondary | AUCt Of Molybdenum With Coadministration Of Celecoxib | 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. | Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data. | Posted | Mean | Standard Deviation | h•ng/mL | Baseline, up to 336 hours post-dose |
|
|
|
| Secondary | AUCinf Of Molybdenum With Coadministration Of Celecoxib | 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. | Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data. | Posted | Mean | Standard Deviation | h•ng/mL | Baseline, up to 336 hours post-dose |
|
|
|
| 35 |
| 0 |
| 35 |
| 8 |
| 35 |
| EG001 | Treatment B | Participants who received celecoxib with ALXN1840. | 0 | 35 | 0 | 35 | 3 | 35 |
| Constipation | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Dental discomfort | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Systematic Assessment |
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| SARS-CoV-2 test positive | Investigations | MedDRA Version 23.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 23.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA Version 23.1 | Systematic Assessment |
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| Menstruation irregular | Reproductive system and breast disorders | MedDRA Version 23.1 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Systematic Assessment |
|
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| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008664 | Metal Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
|