Bioavailability Study of 2 Oral Formulations of ALXN1840

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: ALXN1840

• Registration Number: NCT04610580
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

The study will assess the relative bioavailability of 2 different formulations of ALXN1840 in healthy participants.

Detailed Description

This is a two-way crossover study consisting of 2 dosing periods assessing a test and reference formulation of ALXN1840. A dose-proportionality parallel group design extension period will be conducted following completion of the two-way crossover period of the study and will assess 5 different ascending doses of ALXN1840. There will be at least a 14-day washout following doses between Periods 1 and 2 and also at least a 14-day washout following the dose in Period 2 and the following dose in the Dose-Proportionality Extension Period.

Safety will be assessed throughout the study.

Study Timeline

• Study First Submitted: 2020-10-13
• Study First Submitted QC: 2020-10-29
• Study First Posted: 2020-10-30
• Study Start: 2021-01-31
• Primary Completion: 2021-03-24
• Study Completion: 2021-04-26
• Results First Submitted: 2022-06-08
• Status Verified: 2023-04
• Results First Submitted QC: 2023-04-17
• Last Update Submitted: 2023-04-17
• Results First Posted: 2024-01-16
• Last Update Posted: 2024-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• No clinically significant history or presence of electrocardiogram findings
• Body weight ≥50 to ≤100 kilograms (kg) and body mass index 18 to <32 kg/meter squared for all participants
• Willing and able to follow protocol-specified contraception requirements

Exclusion Criteria

• History or presence of clinical and/or laboratory disorders
• Abnormal blood pressure, defined as supine blood pressure ≤90/60 millimeters of mercury (mmHg) or >140/90 mmHg
• Lymphoma, leukemia, or any malignancy within the past 5 years
• Alanine aminotransferase, aspartate aminotransferase, or total bilirubin > upper limit of normal
• Serum copper or serum ceruloplasmin below lower limit of normal
• Hemoglobin <130 grams (g)/liter (L) for males and hemoglobin <115 g/L for females
• Significant allergies
• Smoker

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Crossover ALXN1840 Sequence 1	ALXN1840	Participants will first receive a single dose of ALXN1840 test formulation on Day 1 of Period 1. After a washout period of 14 days, they will then receive a single dose of ALXN1840 reference formulation on Day 1 of Period 2.
Crossover ALXN1840 Sequence 2	ALXN1840	Participants will first receive a single dose of ALXN1840 reference formulation on Day 1 of Period 1. After a washout period of 14 days, they will then receive a single dose of ALXN1840 test formulation on Day 1 of Period 2.
Parallel Dose-proportionality Extension: ALXN1840 Dose 1	ALXN1840	Participants will receive a single dose of ALXN1840.
Parallel Dose-proportionality Extension: ALXN1840 Dose 3	ALXN1840	Participants will receive a single dose of ALXN1840.
Parallel Dose-proportionality Extension: ALXN1840 Dose 4	ALXN1840	Participants will receive a single dose of ALXN1840.
Parallel Dose-proportionality Extension: ALXN1840 Dose 2	ALXN1840	Participants will receive a single dose of ALXN1840.

Primary Outcome Measures

Name	Time	Method
Two-way Crossover Period: Cmax for PUF Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS.
Two-way Crossover Period: Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) For Plasma Total Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.
Two-way Crossover Period: Maximum Observed Concentration (Cmax) For Plasma Total Molybdenum (Mo)	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of total Mo via inductively coupled plasma-mass spectroscopy (ICP-MS).
Two-way Crossover Period: Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) For Plasma Total Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.
Two-way Crossover Period: AUCt for Plasma PUF Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS.

Secondary Outcome Measures

Name	Time	Method
Dose-Proportionality Extension Period: AUCinf For Plasma Total Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.
Dose-Proportionality Extension Period: AUCt For Plasma PUF Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS.
Dose-Proportionality Extension Period: Cmax For Plasma Total Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.
Dose-Proportionality Extension Period: Cmax For Plasma PUF Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS.
Dose-Proportionality Extension Period: AUCt For Plasma Total Mo	predose (0.5 hour) and up to 336 hours postdose	Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.

Trial Locations

Locations (1)

Nucleus Network Pty Ltd.; 🇦🇺 Melbourne, Victoria, Australia