Healthy
Conditions
Keywords
Copper Balance, Molybdenum Balance, Healthy, ALXN1840
Brief summary
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.
Detailed description
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.
Interventions
DRUGALXN1840
Administered orally as tablets.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Have regular bowel movements (at least once per day). 2. Adequate venous access in the left or right arm to allow collection of study-required blood samples. 3. Willing and able to adhere to all dietary requirements of the study. 4. Body weight between 50 to 70 kilograms (kg) (inclusive) for female participants, and 65 to 85 kg (inclusive) for male participants, and body mass index within the range 18 to 25 kg/meters squared (inclusive). 5. Willing and able to follow protocol-specified contraception requirements. 6. Capable of giving signed informed consent.
Exclusion criteria
1. Significant medical history (current or past). 2. History or presence of gastrointestinal conditions including chronic constipation and irritable bowel syndrome. 3. Supine blood pressure ≤ 90/60 millimeters of mercury (mmHg) or \> 140/90 mmHg. 4. Lymphoma, leukemia, or any malignancy within 3 years. 5. Breast cancer within the past 10 years. 6. Alanine aminotransferase, aspartate aminotransferase, or total bilirubin \> upper limit of normal at Screening. 7. Serum copper or serum ceruloplasmin below lower limit of normal on laboratory reference range at Screening. 8. History of anemia or hemoglobin \< 130 gram (g)/Liter (L) for men and hemoglobin \< 115 g/L for women at Screening. 9. History of benign ethnic neutropenia or absolute neutrophil count \< 1500/microliter (uL), lymphocyte count below 1000/uL. 10. QTcF\> 450 millisecond (ms) for men and QTcF\> 480 ms for women. 11. Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for asymptomatic gallstones).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15) | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Daily Molybdenum Balance at Steady State (Over Days 12 to 15) | Baseline, 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. |
| Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Baseline, 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. |
| Mean Daily Molybdenum Balance Throughout the ALXN1840 Treatment Period (Day 1 Through Day 15) | 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. |
| Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Days 4 to 15 | Copper balance for the Day 4 through Day 15 period included data averaged from Day 4 through Day 15. |
| Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Day 1 through Day 30 | Copper balance for the Day 1 through Day 30 period included data averaged from Day 1 through Day 30. |
| Mean Daily Copper Balance Over Two Weeks of Repeated ALXN1840 Dosing | Day 4 through Day 15 | 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. |
| Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Day 1 through Day 30 | Molybdenum balance for the Day 1 through Day 30 period included data averaged from 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 | — |
| Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Day 15 (predose and 24 hours postdose) | — |
Countries
United Kingdom
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: ALXN1840 Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. | 6 |
| Group 2: ALXN1840 Participants received repeat dose of ALXN1840 tablet administered orally on Day 1 through Day 15. | 11 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Group 1: ALXN1840 | Group 2: ALXN1840 |
|---|---|---|---|
| Age, Continuous | 28.6 years STANDARD_DEVIATION 5.8 | 27.0 years STANDARD_DEVIATION 6.29 | 29.5 years STANDARD_DEVIATION 5.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Mean Daily Copper Balance | 0.5160 milligrams (mg)/day STANDARD_DEVIATION 0.51399 | 0.8538 milligrams (mg)/day STANDARD_DEVIATION 0.48629 | 0.3317 milligrams (mg)/day STANDARD_DEVIATION 0.44568 |
| Mean Daily Molybdenum Balance | 0.0540 mg/day STANDARD_DEVIATION 0.07372 | 0.1286 mg/day STANDARD_DEVIATION 0.04469 | 0.0133 mg/day STANDARD_DEVIATION 0.05035 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 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 | 13 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 3 Participants | 5 Participants |
| Total Molybdenum Excretion in Feces | 0.0675 mg STANDARD_DEVIATION 0.02809 | 0.0586 mg STANDARD_DEVIATION 0.02347 | 0.0724 mg STANDARD_DEVIATION 0.03023 |
| Total Molybdenum Excretion in Urine | 0.1142 mg STANDARD_DEVIATION 0.03268 | 0.1039 mg STANDARD_DEVIATION 0.02656 | 0.1198 mg STANDARD_DEVIATION 0.03546 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 11 | 0 / 17 |
| other Total, other adverse events | 5 / 6 | 9 / 11 | 14 / 17 |
| serious Total, serious adverse events | 0 / 6 | 0 / 11 | 0 / 17 |
Outcome results
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.
Time frame: Baseline, Days 4 to 15
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: ALXN1840 | Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15) | -0.0749 mg/day | Standard Deviation 0.37419 |
| Group 2: ALXN1840 | Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15) | 0.6901 mg/day | Standard Deviation 0.48176 |
| Total (Groups 1 and 2): ALXN1840 | Change From Baseline in Mean Daily Copper Balance Over 2 Weeks of Repeated Daily ALXN1840 Dosing (Over Days 4 to 15) | 0.4201 mg/day | Standard Deviation 0.57518 |
Secondary
Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum
Time frame: Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of Total Molybdenum at Day 1 | 4860.289 hours*ng/mL | Standard Deviation 1078.263 |
| Group 1: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of Total Molybdenum at Day 15 | 6770.905 hours*ng/mL | Standard Deviation 582.77 |
| Group 1: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of PUF Molybdenum at Day 1 | 356.156 hours*ng/mL | Standard Deviation 133.8174 |
| Group 1: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of PUF Molybdenum at Day 15 | 1035.231 hours*ng/mL | Standard Deviation 252.0931 |
| Group 2: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of PUF Molybdenum at Day 15 | 913.807 hours*ng/mL | Standard Deviation 379.175 |
| Group 2: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of Total Molybdenum at Day 1 | 4439.012 hours*ng/mL | Standard Deviation 1374.869 |
| Group 2: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of PUF Molybdenum at Day 1 | 318.123 hours*ng/mL | Standard Deviation 131.9084 |
| Group 2: ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of Total Molybdenum at Day 15 | 7496.724 hours*ng/mL | Standard Deviation 1499.37 |
| Total (Groups 1 and 2): ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of PUF Molybdenum at Day 15 | 962.376 hours*ng/mL | Standard Deviation 329.6126 |
| Total (Groups 1 and 2): ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of Total Molybdenum at Day 15 | 7206.397 hours*ng/mL | Standard Deviation 1241.529 |
| Total (Groups 1 and 2): ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of PUF Molybdenum at Day 1 | 331.546 hours*ng/mL | Standard Deviation 129.699 |
| Total (Groups 1 and 2): ALXN1840 | Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval (AUCtau) of Total Molybdenum and PUF Molybdenum | AUCtau of Total Molybdenum at Day 1 | 4587.698 hours*ng/mL | Standard Deviation 1260.082 |
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.
Time frame: Baseline, Days 12 to 15
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: ALXN1840 | Change From Baseline in Mean Daily Molybdenum Balance at Steady State (Over Days 12 to 15) | 1.7750 mg/day | Standard Deviation 0.98161 |
| Group 2: ALXN1840 | Change From Baseline in Mean Daily Molybdenum Balance at Steady State (Over Days 12 to 15) | 0.6189 mg/day | Standard Deviation 1.24337 |
| Total (Groups 1 and 2): ALXN1840 | Change From Baseline in Mean Daily Molybdenum Balance at Steady State (Over Days 12 to 15) | 1.0269 mg/day | Standard Deviation 1.26161 |
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.
Time frame: Baseline, Days 4 to 15
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Feces | 2.0247 mg | Standard Deviation 0.64199 |
| Group 1: ALXN1840 | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Urine | 2.6210 mg | Standard Deviation 0.68681 |
| Group 2: ALXN1840 | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Feces | 1.9586 mg | Standard Deviation 0.32854 |
| Group 2: ALXN1840 | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Urine | 2.5957 mg | Standard Deviation 0.39688 |
| Total (Groups 1 and 2): ALXN1840 | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Feces | 1.9819 mg | Standard Deviation 0.44421 |
| Total (Groups 1 and 2): ALXN1840 | Change From Baseline in Total Molybdenum Excretion in Urine and Feces Averaged Over 2 Weeks of Dosing (Days 4 to 15) | Urine | 2.6046 mg | Standard Deviation 0.496 |
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.
Time frame: Days 4 to 15
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Food | 1.5039 mg | Standard Deviation 0.10025 |
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Drink | 0.0270 mg | Standard Deviation 0.0012 |
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Feces | 0.7373 mg | Standard Deviation 0.23986 |
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Urine | 0.0147 mg | Standard Deviation 0.01102 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Urine | 0.0173 mg | Standard Deviation 0.0078 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Food | 1.7178 mg | Standard Deviation 0.12247 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Feces | 0.6895 mg | Standard Deviation 0.17102 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Drink | 0.0108 mg | Standard Deviation 0.00194 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Urine | 0.0164 mg | Standard Deviation 0.00881 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Drink | 0.0165 mg | Standard Deviation 0.00816 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Feces | 0.7064 mg | Standard Deviation 0.19187 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine Averaged Over 2 Weeks of Dosing | Copper Quantified in Food | 1.6423 mg | Standard Deviation 0.15366 |
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.
Time frame: Day 1 through Day 30
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Food | 1.6117 mg | Standard Deviation 0.12736 |
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Drink | 0.0252 mg | Standard Deviation 0.00124 |
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Feces | 0.7017 mg | Standard Deviation 0.19009 |
| Group 1: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Urine | 0.0192 mg | Standard Deviation 0.01107 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Urine | 0.0209 mg | Standard Deviation 0.00655 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Food | 1.6673 mg | Standard Deviation 0.12779 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Feces | 0.6962 mg | Standard Deviation 0.13385 |
| Group 2: ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Drink | 0.0124 mg | Standard Deviation 0.00212 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Urine | 0.0203 mg | Standard Deviation 0.00811 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Drink | 0.0169 mg | Standard Deviation 0.00658 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Feces | 0.6982 mg | Standard Deviation 0.14999 |
| Total (Groups 1 and 2): ALXN1840 | Copper Quantified in Food, Drink, Feces, and Urine From Day 1 Through Day 30 | Copper Quantified in Food | 1.6476 mg | Standard Deviation 0.12659 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum
Time frame: Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of Total Molybdenum at Day 1 | 303.000 nanograms (ng)/mL | Standard Deviation 65.3667 |
| Group 1: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of Total Molybdenum at Day 15 | 358.500 nanograms (ng)/mL | Standard Deviation 53.6945 |
| Group 1: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of PUF Molybdenum at Day 1 | 30.445 nanograms (ng)/mL | Standard Deviation 12.0613 |
| Group 1: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of PUF Molybdenum at Day 15 | 93.717 nanograms (ng)/mL | Standard Deviation 42.9368 |
| Group 2: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of PUF Molybdenum at Day 15 | 74.678 nanograms (ng)/mL | Standard Deviation 36.1617 |
| Group 2: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of Total Molybdenum at Day 1 | 291.727 nanograms (ng)/mL | Standard Deviation 100.7324 |
| Group 2: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of PUF Molybdenum at Day 1 | 27.266 nanograms (ng)/mL | Standard Deviation 12.9396 |
| Group 2: ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of Total Molybdenum at Day 15 | 382.333 nanograms (ng)/mL | Standard Deviation 78.2624 |
| Total (Groups 1 and 2): ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of PUF Molybdenum at Day 15 | 82.293 nanograms (ng)/mL | Standard Deviation 38.7152 |
| Total (Groups 1 and 2): ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of Total Molybdenum at Day 15 | 372.800 nanograms (ng)/mL | Standard Deviation 68.3794 |
| Total (Groups 1 and 2): ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of PUF Molybdenum at Day 1 | 28.388 nanograms (ng)/mL | Standard Deviation 12.3515 |
| Total (Groups 1 and 2): ALXN1840 | Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum | Cmax of Total Molybdenum at Day 1 | 295.706 nanograms (ng)/mL | Standard Deviation 87.795 |
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.
Time frame: Day 4 through Day 15
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: ALXN1840 | Mean Daily Copper Balance Over Two Weeks of Repeated ALXN1840 Dosing | 0.7789 mg/day | Standard Deviation 0.20297 |
| Group 2: ALXN1840 | Mean Daily Copper Balance Over Two Weeks of Repeated ALXN1840 Dosing | 1.0218 mg/day | Standard Deviation 0.21279 |
| Total (Groups 1 and 2): ALXN1840 | Mean Daily Copper Balance Over Two Weeks of Repeated ALXN1840 Dosing | 0.9361 mg/day | Standard Deviation 0.23558 |
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.
Time frame: Day 1 through Day 15
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: ALXN1840 | Mean Daily Molybdenum Balance Throughout the ALXN1840 Treatment Period (Day 1 Through Day 15) | 2.5560 mg/day | Standard Deviation 0.73042 |
| Group 2: ALXN1840 | Mean Daily Molybdenum Balance Throughout the ALXN1840 Treatment Period (Day 1 Through Day 15) | 2.2861 mg/day | Standard Deviation 0.35654 |
| Total (Groups 1 and 2): ALXN1840 | Mean Daily Molybdenum Balance Throughout the ALXN1840 Treatment Period (Day 1 Through Day 15) | 2.3813 mg/day | Standard Deviation 0.51367 |
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.
Time frame: Day 1 through Day 30
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Urine | 1.4016 mg | Standard Deviation 0.35415 |
| Group 1: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Feces | 1.0575 mg | Standard Deviation 0.29359 |
| Group 1: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Food | 0.2618 mg | Standard Deviation 0.02275 |
| Group 1: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Drink | 0.0014 mg | Standard Deviation 0.00015 |
| Group 1: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in ALXN1840 Doses Given | 3.5933 mg | Standard Deviation 0.02277 |
| Group 2: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Feces | 0.9949 mg | Standard Deviation 0.16082 |
| Group 2: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Food | 0.1414 mg | Standard Deviation 0.01123 |
| Group 2: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Drink | 0.0017 mg | Standard Deviation 0.00048 |
| Group 2: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Urine | 1.3848 mg | Standard Deviation 0.21874 |
| Group 2: ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in ALXN1840 Doses Given | 3.3625 mg | Standard Deviation 0.28101 |
| Total (Groups 1 and 2): ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in ALXN1840 Doses Given | 3.4439 mg | Standard Deviation 0.24988 |
| Total (Groups 1 and 2): ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Urine | 1.3907 mg | Standard Deviation 0.263 |
| Total (Groups 1 and 2): ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Food | 0.1839 mg | Standard Deviation 0.06129 |
| Total (Groups 1 and 2): ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Feces | 1.0170 mg | Standard Deviation 0.20988 |
| Total (Groups 1 and 2): ALXN1840 | Molybdenum Quantified in ALXN1840 Doses Given and in Food, Drink, Feces, And Urine | Molybdenum Quantified in Drink | 0.0016 mg | Standard Deviation 0.00041 |
Secondary
Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum
Time frame: Predose (within 1 hour prior to dosing) through 24 hours postdose on Day 1 and Day 15
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of PUF Molybdenum at Day 1 | 4.655 ng/mL | Standard Deviation 1.1623 |
| Group 1: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of Total Molybdenum at Day 1 | 143.800 ng/mL | Standard Deviation 35.5348 |
| Group 1: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of PUF Molybdenum at Day 15 | 11.060 ng/mL | Standard Deviation 1.3785 |
| Group 1: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of Total Molybdenum at Day 15 | 218.833 ng/mL | Standard Deviation 23.034 |
| Group 2: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of PUF Molybdenum at Day 1 | 4.785 ng/mL | Standard Deviation 1.6602 |
| Group 2: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of Total Molybdenum at Day 15 | 242.625 ng/mL | Standard Deviation 54.5892 |
| Group 2: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of Total Molybdenum at Day 1 | 140.436 ng/mL | Standard Deviation 53.2088 |
| Group 2: ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of PUF Molybdenum at Day 15 | 11.141 ng/mL | Standard Deviation 2.8492 |
| Total (Groups 1 and 2): ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of PUF Molybdenum at Day 15 | 11.106 ng/mL | Standard Deviation 2.2591 |
| Total (Groups 1 and 2): ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of Total Molybdenum at Day 1 | 141.624 ng/mL | Standard Deviation 46.5492 |
| Total (Groups 1 and 2): ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of Total Molybdenum at Day 15 | 232.429 ng/mL | Standard Deviation 44.2488 |
| Total (Groups 1 and 2): ALXN1840 | Observed Concentration at the End of the Dosing Interval (Ctau) of Total Molybdenum and PUF Molybdenum | Ctau of PUF Molybdenum at Day 1 | 4.739 ng/mL | Standard Deviation 1.466 |
Secondary
Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration
Time frame: Day 15 (predose and 24 hours postdose)
Population: Full analysis set included all participants who received at least 1 dose of ALXN1840. Here, 'number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Total Copper Concentration at Day 15 (predose) | 12.58931 micromoles (μmol)/liter (L) | Standard Deviation 1.63664 |
| Group 1: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Total Copper Concentration at Day 15 (24 hours postdose) | 12.56570 micromoles (μmol)/liter (L) | Standard Deviation 1.342502 |
| Group 1: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | LBC Concentration at Day 15 (predose) | 0.93213 micromoles (μmol)/liter (L) | Standard Deviation 0.262655 |
| Group 1: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | LBC Concentration at Day 15 (24 hours postdose) | 1.04386 micromoles (μmol)/liter (L) | Standard Deviation 0.233526 |
| Group 2: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | LBC Concentration at Day 15 (24 hours postdose) | 0.90612 micromoles (μmol)/liter (L) | Standard Deviation 0.264791 |
| Group 2: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Total Copper Concentration at Day 15 (predose) | 13.87256 micromoles (μmol)/liter (L) | Standard Deviation 1.627496 |
| Group 2: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | LBC Concentration at Day 15 (predose) | 0.82360 micromoles (μmol)/liter (L) | Standard Deviation 0.160887 |
| Group 2: ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Total Copper Concentration at Day 15 (24 hours postdose) | 14.49816 micromoles (μmol)/liter (L) | Standard Deviation 1.548441 |
| Total (Groups 1 and 2): ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | LBC Concentration at Day 15 (24 hours postdose) | 0.95777 micromoles (μmol)/liter (L) | Standard Deviation 0.254932 |
| Total (Groups 1 and 2): ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Total Copper Concentration at Day 15 (24 hours postdose) | 13.77349 micromoles (μmol)/liter (L) | Standard Deviation 1.72423 |
| Total (Groups 1 and 2): ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | LBC Concentration at Day 15 (predose) | 0.86190 micromoles (μmol)/liter (L) | Standard Deviation 0.201482 |
| Total (Groups 1 and 2): ALXN1840 | Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration | Total Copper Concentration at Day 15 (predose) | 13.41964 micromoles (μmol)/liter (L) | Standard Deviation 1.700617 |