Wilson Disease
Conditions
Keywords
Copper Balance, Molybdenum Balance, Wilson Disease, ALXN1840
Brief summary
This exploratory study will investigate the effects of ALXN1840 on copper balance in participants with Wilson disease (WD).
Detailed description
Participants who are treatment experienced (which includes standard-of-care therapies or ALXN1840) and treatment naïve are eligible for this study.
Interventions
DRUGALXN1840
Administered orally as tablets.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of WD by Leipzig Criteria ≥ 4. 2. Able to reside in the clinical research unit for intensive metabolic monitoring of copper and molybdenum. 3. Participants willing to adhere to copper/molybdenum-controlled diet during the study. 4. Willing and able to follow protocol-specified contraception requirements. 5. Capable of giving signed informed consent.
Exclusion criteria
1. Decompensated cirrhosis or model for end stage liver disease score \> 13. 2. Modified Nazer score \> 7. 3. Clinically significant gastrointestinal bleed within past 3 months. 4. Alanine aminotransferase \> 2 × upper limit of normal. 5. Hemoglobin less than lower limit of the reference range for age and sex. 6. Significant medical history (current or past). 7. Previous treatment with zinc within 30 days prior to the Screening Visit. 8. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5) or creatinine clearance \< 30 milliliters/minute.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Copper Balance: Day 1 Through Day 8 | Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. |
| Mean Daily Copper Balance: Day 31 Through Day 35 | Accumulation: Day 31 through Day 35 (ALXN1840 30 mg) | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. |
| Mean Daily Copper Balance: Day 25 Through Day 28 | Accumulation: Day 25 through Day 28 (ALXN1840 15 mg) | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. |
| Mean Daily Copper Balance: Day 36 Through Day 39 | Accumulation: Day 36 through Day 39 (ALXN1840 30 mg) | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Molybdenum Balance At ALXN1840 Steady State | Steady state: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | Molybdenum balance at steady state was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine). Steady state is defined as molybdenum (out) equal to molybdenum (in). |
| Accumulation Of Molybdenum As Determined By Molybdenum Balance | Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 ((ALXN1840 30 mg) | Molybdenum balance was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine). |
| Change From Baseline In Mean Daily Copper Balance | Accumulation: Baseline, Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 (ALXN1840 30 mg); Steady State: Baseline, Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. |
| Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Day 39 | — |
| Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Day 1 up to Day 39 | — |
| Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Accumulation: Day 1 through Day 8 for 15 mg and Day 31 through Day 35 for 30 mg; Steady state: Day 25 through Day 28 for ALXN1840 15 mg and Day 36 through Day 39 for ALXN1840 30 mg | Copper was assessed through measurement of copper intake (in food and drink), and copper output (in feces and urine) as well as plasma total and labile bound copper. |
| Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | The amount of molybdenum in food, drink, feces and urine is reported in this outcome measure. |
| Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Accumulation: Baseline, Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 (ALXN1840 30 mg); Steady State: Baseline, Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | — |
Countries
New Zealand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants who had received Wilson disease therapy for \>28 days prior to enrollment were administered ALXN1840 at a dose of 15 mg/day on Day 1 through Day 28 and then increased to 30 mg/day on Day 29 through Day 39. | 8 |
| Cohort 2 Participants who had received Wilson disease therapy for ≤28 days were administered ALXN1840 at a dose of 15 mg/day on Day 1 through Day 28 and then increased to 30 mg/day on Day 29 through Day 39. | 1 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 2 | Total | Cohort 1 |
|---|---|---|---|
| Age, Continuous | 26.0 years | 34.1 years STANDARD_DEVIATION 12 | 35.1 years STANDARD_DEVIATION 12.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 9 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 1 |
| other Total, other adverse events | 6 / 8 | 1 / 1 |
| serious Total, serious adverse events | 0 / 8 | 0 / 1 |
Outcome results
Primary
Mean Daily Copper Balance: Day 1 Through Day 8
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Time frame: Accumulation: Day 1 through Day 8 (ALXN1840 15 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Daily Copper Balance: Day 1 Through Day 8 | 0.8025 milligrams/day | Standard Deviation 0.2686 |
| Cohort 2 | Mean Daily Copper Balance: Day 1 Through Day 8 | 0.3062 milligrams/day | — |
Primary
Mean Daily Copper Balance: Day 25 Through Day 28
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Time frame: Accumulation: Day 25 through Day 28 (ALXN1840 15 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Daily Copper Balance: Day 25 Through Day 28 | 0.7109 milligrams/day | Standard Deviation 0.67915 |
| Cohort 2 | Mean Daily Copper Balance: Day 25 Through Day 28 | 0.7072 milligrams/day | — |
Primary
Mean Daily Copper Balance: Day 31 Through Day 35
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Time frame: Accumulation: Day 31 through Day 35 (ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Daily Copper Balance: Day 31 Through Day 35 | 0.9156 milligrams/day | Standard Deviation 0.37982 |
| Cohort 2 | Mean Daily Copper Balance: Day 31 Through Day 35 | 0.6613 milligrams/day | — |
Primary
Mean Daily Copper Balance: Day 36 Through Day 39
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Time frame: Accumulation: Day 36 through Day 39 (ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean Daily Copper Balance: Day 36 Through Day 39 | 0.9975 milligrams/day | Standard Deviation 0.26543 |
| Cohort 2 | Mean Daily Copper Balance: Day 36 Through Day 39 | 0.5662 milligrams/day | — |
Secondary
Accumulation Of Molybdenum As Determined By Molybdenum Balance
Molybdenum balance was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine).
Time frame: Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 ((ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Accumulation Of Molybdenum As Determined By Molybdenum Balance | Days 1 through 8 | 2.2458 milligrams | Standard Deviation 0.23232 |
| Cohort 1 | Accumulation Of Molybdenum As Determined By Molybdenum Balance | Days 31 through 35 | 2.6265 milligrams | Standard Deviation 1.96365 |
| Cohort 2 | Accumulation Of Molybdenum As Determined By Molybdenum Balance | Days 1 through 8 | 2.0876 milligrams | — |
| Cohort 2 | Accumulation Of Molybdenum As Determined By Molybdenum Balance | Days 31 through 35 | 4.0775 milligrams | — |
Secondary
Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum
Time frame: Day 39
Population: Pharmacokinetic analysis set included all participants who had sufficient plasma samples to enable the calculation of PK parameters and provide PK profiles. Here, Number of participants analyzed signifies those who were evaluable for this outcome measure and number analyzed signifies those who were evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Plasma ultrafiltrate molybdenum | 292.737 hours*nanograms/milliliters | Geometric Coefficient of Variation 11.9 |
| Cohort 1 | Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Total Molydenum | 13532.591 hours*nanograms/milliliters | Geometric Coefficient of Variation 49.3 |
| Cohort 2 | Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Total Molydenum | 65694.679 hours*nanograms/milliliters | — |
| Cohort 2 | Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Plasma ultrafiltrate molybdenum | 476.960 hours*nanograms/milliliters | — |
Secondary
Change From Baseline In Mean Daily Copper Balance
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Time frame: Accumulation: Baseline, Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 (ALXN1840 30 mg); Steady State: Baseline, Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline In Mean Daily Copper Balance | Day 1 through Day 8 | -0.3780 milligrams/day | Standard Deviation 0.14822 |
| Cohort 1 | Change From Baseline In Mean Daily Copper Balance | Day 25 through Day 28 | -0.4697 milligrams/day | Standard Deviation 0.5577 |
| Cohort 1 | Change From Baseline In Mean Daily Copper Balance | Day 31 through Day 35 | -0.2650 milligrams/day | Standard Deviation 0.47135 |
| Cohort 1 | Change From Baseline In Mean Daily Copper Balance | Day 36 through Day 39 | -0.1831 milligrams/day | Standard Deviation 0.44589 |
| Cohort 2 | Change From Baseline In Mean Daily Copper Balance | Day 36 through Day 39 | 0.0540 milligrams/day | — |
| Cohort 2 | Change From Baseline In Mean Daily Copper Balance | Day 1 through Day 8 | -0.2060 milligrams/day | — |
| Cohort 2 | Change From Baseline In Mean Daily Copper Balance | Day 31 through Day 35 | 0.1492 milligrams/day | — |
| Cohort 2 | Change From Baseline In Mean Daily Copper Balance | Day 25 through Day 28 | 0.1950 milligrams/day | — |
Secondary
Change From Baseline In Total Molybdenum Excretion In Urine And Feces
Time frame: Accumulation: Baseline, Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 (ALXN1840 30 mg); Steady State: Baseline, Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Day 1 through 8 | 0.7102 milligrams | Standard Deviation 0.22072 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Day 1 through 8 | 0.3972 milligrams | Standard Deviation 0.15972 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Days 31 through 35 | 1.0484 milligrams | Standard Deviation 0.62291 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Days 25 through 28 | 0.6122 milligrams | Standard Deviation 0.28154 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Days 25 through 28 | 1.0146 milligrams | Standard Deviation 0.42658 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Days 36 through 39 | 0.9683 milligrams | Standard Deviation 0.88027 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Days 36 through 39 | 0.7855 milligrams | Standard Deviation 0.5882 |
| Cohort 1 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Days 31 through 35 | 0.7974 milligrams | Standard Deviation 0.47607 |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Days 36 through 39 | 0.8926 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Day 1 through 8 | 0.9510 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Days 25 through 28 | 0.9736 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Days 31 through 35 | 1.7188 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Feces Content : Days 36 through 39 | 2.0432 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Day 1 through 8 | 0.1725 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Days 25 through 28 | 0.4010 milligrams | — |
| Cohort 2 | Change From Baseline In Total Molybdenum Excretion In Urine And Feces | Molybdenum Urine Content : Days 31 through 35 | 0.8085 milligrams | — |
Secondary
Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC)
Copper was assessed through measurement of copper intake (in food and drink), and copper output (in feces and urine) as well as plasma total and labile bound copper.
Time frame: Accumulation: Day 1 through Day 8 for 15 mg and Day 31 through Day 35 for 30 mg; Steady state: Day 25 through Day 28 for ALXN1840 15 mg and Day 36 through Day 39 for ALXN1840 30 mg
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 1 through Day 8 | 1.6423 milligrams | Standard Deviation 0.15638 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 25 through Day 28 | 1.8269 milligrams | Standard Deviation 0.42485 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 31 through Day 35 | 1.8938 milligrams | Standard Deviation 0.21846 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 36 through Day 39 | 1.7850 milligrams | Standard Deviation 0.20107 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 1 through Day 8 | 0.0061 milligrams | Standard Deviation 0.00159 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 25 through Day 28 | 0.0066 milligrams | Standard Deviation 0.0018 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 31 through Day 35 | 0.0071 milligrams | Standard Deviation 0.00184 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 36 through Day 39 | 0.0118 milligrams | Standard Deviation 0.0092 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 1 through Day 8 | 0.7594 milligrams | Standard Deviation 0.21993 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 25 through Day 28 | 0.9373 milligrams | Standard Deviation 0.30688 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 31 through Day 35 | 0.8270 milligrams | Standard Deviation 0.33746 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 36 through Day 39 | 0.6136 milligrams | Standard Deviation 0.27213 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 1 through Day 8 | 0.0865 milligrams | Standard Deviation 0.05689 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 25 through Day 28 | 0.1852 milligrams | Standard Deviation 0.09079 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 31 through Day 35 | 0.1584 milligrams | Standard Deviation 0.07823 |
| Cohort 1 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 36 through Day 39 | 0.1857 milligrams | Standard Deviation 0.09506 |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 36 through Day 39 | 0.0994 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 1 through Day 8 | 1.3523 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 1 through Day 8 | 0.7718 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 25 through Day 28 | 1.5637 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 1 through Day 8 | 0.2798 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 31 through Day 35 | 1.6022 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 25 through Day 28 | 0.7238 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Food Content: Day 36 through Day 39 | 1.4397 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 31 through Day 35 | 0.0732 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 1 through Day 8 | 0.0055 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 31 through Day 35 | 0.8720 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 25 through Day 28 | 0.0080 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Urine Content: Day 25 through Day 28 | 0.1408 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 31 through Day 35 | 0.0044 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Feces Content: Day 36 through Day 39 | 0.7787 milligrams | — |
| Cohort 2 | Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper Drink Content: Day 36 through Day 39 | 0.0045 milligrams | — |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum
Time frame: Day 1 up to Day 39
Population: Pharmacokinetic (PK) analysis set included all participants who had sufficient plasma samples to enable the calculation of PK parameters and provide PK profiles.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Total Molydenum | 430.451 nanograms/milliliters | Geometric Coefficient of Variation 46.6 |
| Cohort 1 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Plasma ultrafiltrate molybdenum | 13.546 nanograms/milliliters | Geometric Coefficient of Variation 43.5 |
| Cohort 2 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Total Molydenum | 1271.551 nanograms/milliliters | — |
| Cohort 2 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Plasma ultrafiltrate molybdenum | 17.823 nanograms/milliliters | — |
Secondary
Mean Daily Molybdenum Balance At ALXN1840 Steady State
Molybdenum balance at steady state was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine). Steady state is defined as molybdenum (out) equal to molybdenum (in).
Time frame: Steady state: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean Daily Molybdenum Balance At ALXN1840 Steady State | Days 25 through 28 | 1.3618 milligrams/day | Standard Deviation 0.44254 |
| Cohort 1 | Mean Daily Molybdenum Balance At ALXN1840 Steady State | Days 36 through 39 | 2.7599 milligrams/day | Standard Deviation 1.68008 |
| Cohort 2 | Mean Daily Molybdenum Balance At ALXN1840 Steady State | Days 25 through 28 | 2.1087 milligrams/day | — |
| Cohort 2 | Mean Daily Molybdenum Balance At ALXN1840 Steady State | Days 36 through 39 | 3.6581 milligrams/day | — |
Secondary
Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State
The amount of molybdenum in food, drink, feces and urine is reported in this outcome measure.
Time frame: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840 treatment. Here, Number of Participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Food Content : Days 25 through 28 | 0.3324 milligrams | Standard Deviation 0.18039 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Food Content : Days 36 through 39 | 0.1923 milligrams | Standard Deviation 0.02354 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Drink Content : Days 25 through 28 | 0.0006 milligrams | Standard Deviation 0.00012 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Drink Content : Days 36 through 39 | 0.0007 milligrams | Standard Deviation 0.00024 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Feces Content : Days 25 through 28 | 1.1004 milligrams | Standard Deviation 0.38506 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Feces Content : Days 36 through 39 | 1.0541 milligrams | Standard Deviation 0.83207 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Urine Content : Days 25 through 28 | 0.7250 milligrams | Standard Deviation 0.32736 |
| Cohort 1 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Urine Content : Days 36 through 39 | 0.8984 milligrams | Standard Deviation 0.62633 |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Urine Content : Days 36 through 39 | 1.0395 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Food Content : Days 25 through 28 | 0.3905 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Feces Content : Days 25 through 28 | 1.0656 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Food Content : Days 36 through 39 | 0.1724 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Urine Content : Days 25 through 28 | 0.5480 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Drink Content : Days 25 through 28 | 0.0018 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Feces Content : Days 36 through 39 | 2.1352 milligrams | — |
| Cohort 2 | Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | Molybdenum Drink Content : Days 36 through 39 | 0.0004 milligrams | — |