Bioavailability Study of 2 Oral Formulations of ALXN1840

• ClinicalTrials.gov Identifier: NCT04610580
• Recruitment Status: Completed
• First Posted: October 30, 2020
• Last Update Posted: July 28, 2021
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: ALXN1840	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This is a 2-period, 2-sequence, crossover study with a parallel group extension.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, 2-period, 2-sequence, Crossover With Parallel-group Extension, Open-label Study to Compare the Relative Bioavailability of 2 Oral Formulations of ALXN1840 in Healthy Adult Participants
• Actual Study Start Date: January 31, 2021
• Actual Primary Completion Date: March 24, 2021
• Actual Study Completion Date: April 26, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Crossover ALXN1840 Sequence 1; 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.	Drug: ALXN1840; ALXN1840 will be administered orally.
Experimental: Crossover ALXN1840 Sequence 2; 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.	Drug: ALXN1840; ALXN1840 will be administered orally.
Experimental: Parallel Dose-proportionality Extension: ALXN1840 Dose 1; Participants will receive a single dose of ALXN1840.	Drug: ALXN1840; ALXN1840 will be administered orally.
Experimental: Parallel Dose-proportionality Extension: ALXN1840 Dose 2; Participants will receive a single dose of ALXN1840.	Drug: ALXN1840; ALXN1840 will be administered orally.
Experimental: Parallel Dose-proportionality Extension: ALXN1840 Dose 3; Participants will receive a single dose of ALXN1840.	Drug: ALXN1840; ALXN1840 will be administered orally.
Experimental: Parallel Dose-proportionality Extension: ALXN1840 Dose 4; Participants will receive a single dose of ALXN1840.	Drug: ALXN1840; ALXN1840 will be administered orally.

Outcome Measures

Primary Outcome Measures :

1. Relative Bioavailability Of ALXN1840 Test And Reference Formulations As Assessed By Maximum Observed Concentration (Cmax) For Plasma Total Molybdenum (Mo) and Plasma Ultrafiltrate (PUF) Mo [ Time Frame: Period 1: up to 336 hours postdose and Period 2: up to 336 hours postdose ]
2. Relative Bioavailability Of ALXN1840 Test And Reference Formulations As Assessed By Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) For Plasma Total Mo and PUF Mo [ Time Frame: Period 1: up to 336 hours postdose and Period 2: up to 336 hours postdose ]
3. Relative Bioavailability Of ALXN1840 Test And Reference Formulations As Assessed By Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) For Plasma Total Mo and PUF Mo [ Time Frame: Period 1: up to 336 hours postdose and Period 2: up to 336 hours postdose ]

Secondary Outcome Measures :

1. Extension Period: Dose-proportionality Between 4 Ascending Doses Of ALXN1840 As Assessed by Dose-normalized Cmax For Plasma Total Mo and PUF Mo [ Time Frame: up to 336 hours postdose ]
2. Extension Period: Dose-proportionality Between 4 Ascending Doses Of ALXN1840 As Assessed by Dose-normalized AUCt For Plasma Total Mo and PUF Mo [ Time Frame: up to 336 hours postdose ]
3. Extension Period: Dose-proportionality Between 4 Ascending Doses Of ALXN1840 As Assessed by Dose-normalized AUCinf For Plasma Total Mo and PUF Mo [ Time Frame: up to 336 hours postdose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Australia, Victoria

Nucleus Network Pty Ltd.

Melbourne, Victoria, Australia, 3004

Sponsors and Collaborators

Alexion Pharmaceuticals

More Information

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04610580
• Other Study ID Numbers: ALXN1840-HV-109
• First Posted: October 30, 2020
• Last Update Posted: July 28, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Alexion Pharmaceuticals:

Bioavailability; Healthy