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The study will assess the change from baseline in mean daily copper balance in healthy participants with repeat-dose administrations of ALXN1840 over 2 weeks.
This study will also characterize the steady state absorption, distribution, metabolism, and excretion (mass balance) of total molybdenum, which is a surrogate measure of ALXN1840 disposition.
Safety will be monitored throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALXN1840 | Experimental | Participants will be administered repeat doses of ALXN1840 30 milligrams (mg) for 15 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALXN1840 | Drug | Administered orally as tablets. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15) | Copper balance was defined as the difference in copper input and copper output. A negative copper balance indicated greater copper output than copper intake. Copper input was defined as the sum of all copper input as measured in all food and fluids over the specified period. Copper output was defined as the sum of all copper output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1. | Baseline, Days 4 to 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Daily Copper Balance Over Two Weeks of Repeated ALXN1840 Dosing | Copper balance was defined by the difference in copper input and copper output. A negative copper balance indicated greater copper output than copper intake. Copper input was defined as the sum of all copper input as measured in all food and fluids over the specified period. Copper output was defined as the sum of all copper output as measured in urine and feces over the specified collection period. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eugene S. Swenson, MD, PhD | Alexion Pharmaceuticals, Inc. | Study Director |
| Peter Ksenuk, MD | Alexion Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Study Site | London | United Kingdom |
A total of 17 participants were enrolled in 2 groups. Group 1 consisted of 6 participants. Group 2, consisting of 11 participants, was initiated after the Safety Review Committee (SRC) reviewed safety information from Group 1. No safety concerns were identified; therefore, no dose adjustments were implemented with Group 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
| FG001 | Group 2: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Full analysis set included all participants who received at least 1 dose of ALXN1840.
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
| BG001 | Group 2: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
| 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 | Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15) | Copper balance was defined as the difference in copper input and copper output. A negative copper balance indicated greater copper output than copper intake. Copper input was defined as the sum of all copper input as measured in all food and fluids over the specified period. Copper output was defined as the sum of all copper output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg/day | Baseline, Days 4 to 15 |
|
Baseline up to Day 43
Safety set included all participants who received at least 1 dose of ALXN1840.
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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 | Group 1: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | +1 855-752-2356 | 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 | May 29, 2020 | Aug 30, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 20, 2020 | Aug 30, 2022 | SAP_001.pdf |
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| Day 4 through Day 15 |
| Change From Baseline in Mean Daily Molybdenum Balance at Steady State (Over Days 12 to 15) | Molybdenum mass balance was defined as the difference in molybdenum input and molybdenum output. A negative molybdenum balance indicated greater molybdenum output than molybdenum intake. Molybdenum input was defined as the sum of all molybdenum input as measured in all food and fluids over the specified period. Molybdenum output was defined as the sum of all molybdenum output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1. | Baseline, Days 12 to 15 |
| Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Molybdenum mass balance was defined as the difference in molybdenum input and molybdenum output. A negative molybdenum balance indicated greater molybdenum output than molybdenum intake. Molybdenum input was defined as the sum of all molybdenum input as measured in all food and fluids over the specified period. Molybdenum output was defined as the sum of all molybdenum output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1. Molybdenum excretion for the Day 4 through Day 15 period included data averaged from Day 4 through Day 15. | Baseline, Days 4 to 15 |
| Mean Daily Molybdenum Balance Throughout the ALXN1840 Treatment Period (Day 1 Through Day 15) | Molybdenum mass balance was defined as the difference in molybdenum input and molybdenum output. A negative molybdenum balance indicated greater molybdenum output than molybdenum intake. Molybdenum input was defined as the sum of all molybdenum input as measured in all food and fluids over the specified period. Molybdenum output was defined as the sum of all molybdenum output as measured in urine and feces over the specified collection period. | Day 1 through Day 15 |
| Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper balance for the Day 4 through Day 15 period included data averaged from Day 4 through Day 15. | Days 4 to 15 |
| Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper balance for the Day 1 through Day 30 period included data averaged from Day 1 through Day 30. | Day 1 through Day 30 |
| Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Day 15 (predose and 24 hours postdose) |
| Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum balance for the Day 1 through Day 30 period included data averaged from Day 1 through Day 30. | Day 1 through Day 30 |
| Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15 |
| Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15 |
| Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15 |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Mean Daily Copper Balance | Mean | Standard Deviation | milligrams (mg)/day |
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| Mean Daily Molybdenum Balance | Mean | Standard Deviation | mg/day |
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| Total Molybdenum Excretion in Feces | Mean | Standard Deviation | mg |
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| Total Molybdenum Excretion in Urine | Mean | Standard Deviation | mg |
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| OG001 | Group 2: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
| OG002 | Total (Groups 1 and 2): ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. |
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| Secondary | Mean Daily Copper Balance Over Two Weeks of Repeated ALXN1840 Dosing | Copper balance was defined by the difference in copper input and copper output. A negative copper balance indicated greater copper output than copper intake. Copper input was defined as the sum of all copper input as measured in all food and fluids over the specified period. Copper output was defined as the sum of all copper output as measured in urine and feces over the specified collection period. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg/day | Day 4 through Day 15 |
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| Secondary | Change From Baseline in Mean Daily Molybdenum Balance at Steady State (Over Days 12 to 15) | Molybdenum mass balance was defined as the difference in molybdenum input and molybdenum output. A negative molybdenum balance indicated greater molybdenum output than molybdenum intake. Molybdenum input was defined as the sum of all molybdenum input as measured in all food and fluids over the specified period. Molybdenum output was defined as the sum of all molybdenum output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg/day | Baseline, Days 12 to 15 |
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| Secondary | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Molybdenum mass balance was defined as the difference in molybdenum input and molybdenum output. A negative molybdenum balance indicated greater molybdenum output than molybdenum intake. Molybdenum input was defined as the sum of all molybdenum input as measured in all food and fluids over the specified period. Molybdenum output was defined as the sum of all molybdenum output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1. Molybdenum excretion for the Day 4 through Day 15 period included data averaged from Day 4 through Day 15. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg | Baseline, Days 4 to 15 |
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| Secondary | Mean Daily Molybdenum Balance Throughout the ALXN1840 Treatment Period (Day 1 Through Day 15) | Molybdenum mass balance was defined as the difference in molybdenum input and molybdenum output. A negative molybdenum balance indicated greater molybdenum output than molybdenum intake. Molybdenum input was defined as the sum of all molybdenum input as measured in all food and fluids over the specified period. Molybdenum output was defined as the sum of all molybdenum output as measured in urine and feces over the specified collection period. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg/day | Day 1 through Day 15 |
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| Secondary | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper balance for the Day 4 through Day 15 period included data averaged from Day 4 through Day 15. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg | Days 4 to 15 |
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| Secondary | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper balance for the Day 1 through Day 30 period included data averaged from Day 1 through Day 30. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg | Day 1 through Day 30 |
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| Secondary | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Full analysis set included all participants who received at least 1 dose of ALXN1840. Here, 'number analyzed' signifies participants evaluable for specified categories. | Posted | Mean | Standard Deviation | micromoles (μmol)/liter (L) | Day 15 (predose and 24 hours postdose) |
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| Secondary | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum balance for the Day 1 through Day 30 period included data averaged from Day 1 through Day 30. | Full analysis set included all participants who received at least 1 dose of ALXN1840. | Posted | Mean | Standard Deviation | mg | Day 1 through Day 30 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Pharmacokinetic (PK) analysis set included all participants who had sufficient samples to enable the calculation of PK parameters and provide PK profiles. Here, 'number analyzed' signifies participants evaluable for specified categories. | Posted | Mean | Standard Deviation | nanograms (ng)/mL | Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15 |
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| Secondary | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | PK analysis set included all participants who had sufficient samples to enable the calculation of PK parameters and provide PK profiles. Here, 'number analyzed' signifies participants evaluable for specified categories. | Posted | Mean | Standard Deviation | hours*ng/mL | Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15 |
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| Secondary | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | PK analysis set included all participants who had sufficient samples to enable the calculation of PK parameters and provide PK profiles. Here, 'number analyzed' signifies participants evaluable for specified categories. | Posted | Mean | Standard Deviation | ng/mL | Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15 |
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| 0 |
| 6 |
| 0 |
| 6 |
| 5 |
| 6 |
| EG001 | Group 2: ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. | 0 | 11 | 0 | 11 | 9 | 11 |
| EG002 | Total (Groups 1 and 2): ALXN1840 | Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. | 0 | 17 | 0 | 17 | 14 | 17 |
| Dyspepsia | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Catheter site haematoma | General disorders | MedDRA (23.1) | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
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| Liver function test abnormal | Investigations | MedDRA (23.1) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
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| Renal cyst | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (23.1) | Systematic Assessment | This is a gender-specific AE. Only female participants were at risk. |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Dandruff | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Ingrown hair | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
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| Copper Quantified in Feces |
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| Copper Quantified in Urine |
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| Copper Quantified in Feces |
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| Copper Quantified in Urine |
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| Total Copper Concentration at Day 15 (24 hours postdose) |
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| LBC Concentration at Day 15 (predose) |
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| LBC Concentration at Day 15 (24 hours postdose) |
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| Molybdenum Quantified in Feces |
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| Molybdenum Quantified in Urine |
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| Molybdenum Quantified in ALXN1840 Doses Given |
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| Cmax of Total Molybdenum at Day 15 |
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| Cmax of PUF Molybdenum at Day 1 |
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| Cmax of PUF Molybdenum at Day 15 |
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| AUCtau of Total Molybdenum at Day 15 |
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| AUCtau of PUF Molybdenum at Day 1 |
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| AUCtau of PUF Molybdenum at Day 15 |
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| Ctau of Total Molybdenum at Day 15 |
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| Ctau of PUF Molybdenum at Day 1 |
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| Ctau of PUF Molybdenum at Day 15 |
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