Copper Balance in Healthy Participants Administered ALXN1840

A Phase 1, Open-label Study to Assess Copper Balance in Healthy Participants Following Administration of ALXN1840

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ALXN1840

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1840; Participants will be administered repeat doses of ALXN1840 30 milligrams (mg) for 15 days.	Drug: ALXN1840; Administered orally as tablets.; Other Names: formerly WTX101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Investigators: Study Director: Eugene S. Swenson, MD, PhD, Alexion Pharmaceuticals, Inc.; Study Director: Peter Ksenuk, MD, Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): November 18, 2020

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Healthy; Copper Balance; Molybdenum Balance; ALXN1840
• Other Study ID Numbers: ALXN1840-HV-108

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No