Copper Balance in Healthy Participants Administered ALXN1840

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: ALXN1840

• Registration Number: NCT04594252
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

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.

Study Timeline

• Study Start: 2020-07-01
• Study First Submitted: 2020-09-28
• Study First Submitted QC: 2020-10-16
• Study First Posted: 2020-10-20
• Primary Completion: 2020-11-18
• Study Completion: 2020-11-18
• Results First Submitted: 2022-08-30
• Status Verified: 2024-03
• Results First Submitted QC: 2024-03-21
• Last Update Submitted: 2024-03-21
• Results First Posted: 2024-08-19
• Last Update Posted: 2024-08-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ALXN1840	ALXN1840	Participants will be administered repeat doses of ALXN1840 30 milligrams (mg) for 15 days.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
Plasma Total Copper Concentration and Labile Bound Copper (LBC) Concentration	Day 15 (predose and 24 hours postdose)
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.
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.
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

Trial Locations

Locations (1)

Clinical Study Site; 🇬🇧 London, United Kingdom