A Study of ALXN1840 (Non-coated) Administered With And Without Omeprazole In Healthy Adults

Study Overview
=================
Brief Summary
-----------------
This was single-center, open-label, randomized, 3-period, 3-treatment, 6-sequence crossover study evaluating the PK of single doses of WTX101 in healthy participants based on the measurement of plasma total Molybdenum.

Official Title
-----------------
A Phase 1, Single-Center, Randomized, 3-Period Crossover Study to Evaluate the Relative Bioavailability of WTX101 in Healthy Subjects After Single Dose Administration of a Non-Coated Formulation With and Without a Proton Pump Inhibitor and With a Proton Pump Inhibitor With and Without Food

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: ALXN1840
* Drug: Omeprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-smoker Medically healthy with no clinically significant laboratory profiles, vital signs, or electrocardiograms. Body mass index ≥ 18 and ≤ 32.0 kilograms/meter squared. Willing and able to adhere to contraception requirements. Exclusion Criteria: Participant was mentally or legally incapacitated History or presence of clinically significant medical or psychiatric condition or disease. History of any illness that might have interfered with drug absorption. History or presence of hypersensitivity or idiosyncratic reaction to the study medications, study medication excipients. History or presence of alcoholism or drug abuse. Female participants who were pregnant or lactating. Positive results at screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus. Serum ceruloplasmin and copper values outside of the normal range at screening. On a diet incompatible with the on-study diet within the 28 days prior to the first ALXN1840 dose and throughout the study; unable to consume the contents of a high-fat breakfast. Participation in a previous clinical trial with ALXN1840.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This was single-center, open-label, randomized, 3-period, 3-treatment, 6-sequence crossover study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: ABC<br>Participants received each treatment on 1 occasion: Period 1 (Treatment A): ALXN1840 following an overnight fast. Period 2 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 3 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. There was a washout period of at least 14 days between each ALXN1840 dosing. | Drug: ALXN1840<br>* ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.<br>* Other names: Tiomolibdate choline;Drug: Omeprazole<br>* Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1.<br>* Other names: Prilosec;|
| Experimental: Sequence 2: ACB<br>Participants received each treatment on 1 occasion: Period 1 (Treatment A): ALXN1840 following an overnight fast. Period 2 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 3 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. | Drug: ALXN1840<br>* ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.<br>* Other names: Tiomolibdate choline;Drug: Omeprazole<br>* Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1.<br>* Other names: Prilosec;|
| Experimental: Sequence 3: BAC<br>Participants received each treatment on 1 occasion: Period 1 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 2 (Treatment A): ALXN1840 following an overnight fast. Period 3 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. There was a washout period of at least 14 days between each ALXN1840 dosing. | Drug: ALXN1840<br>* ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.<br>* Other names: Tiomolibdate choline;Drug: Omeprazole<br>* Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1.<br>* Other names: Prilosec;|
| Experimental: Sequence 4: BCA<br>Participants received each treatment on 1 occasion: Period 1 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 2 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 3 (Treatment A): ALXN1840 following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. | Drug: ALXN1840<br>* ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.<br>* Other names: Tiomolibdate choline;Drug: Omeprazole<br>* Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1.<br>* Other names: Prilosec;|
| Experimental: Sequence 5: CAB<br>Participants received each treatment on 1 occasion: Period 1 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 2 (Treatment A): ALXN1840 following an overnight fast. Period 3 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. | Drug: ALXN1840<br>* ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.<br>* Other names: Tiomolibdate choline;Drug: Omeprazole<br>* Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1.<br>* Other names: Prilosec;|
| Experimental: Sequence 6: CBA<br>Participants received each treatment on 1 occasion: Period 1 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 2 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 3 (Treatment A): ALXN1840 following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. | Drug: ALXN1840<br>* ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.<br>* Other names: Tiomolibdate choline;Drug: Omeprazole<br>* Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1.<br>* Other names: Prilosec;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Total Molybdenum (Mo) | AUC0-t was calculated by the linear trapezoidal method. | Predose (0 hour) up to 192 hours postdose | 
| Maximum Measured Plasma Concentration (Cmax) of Total Mo |  | Predose (0 hour) up to 192 hours postdose | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with the study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A TEAE was defined as an AE that started or worsened at the time of or after study drug administration. An AE that occurred during the washout period between drugs was considered treatment emergent to the last drug given. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. | Day 1 through 14 days following final dose (up to Day 43) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
WTX101, ALXN1840, Omeprazole