A Bioequivalence Study of the Lu AA21004 20 mg and 2×10 mg Tablets

A Randomized, Open-Label, 2×2 Crossover Phase 1 Study to Evaluate the Bioequivalence of Single Oral Dose of Lu AA21004 20 mg Tablet and 2× Lu AA21004 10 mg Tablets in Healthy Adult Subjects

The purpose of this study is to evaluate the bioequivalence of a single oral administration of a vortioxetine (Lu AA21004) 20 mg tablet in comparison with two of vortioxetine 10 mg tablets in Japanese healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Participants
• Intervention / Treatment: Drug: Vortioxetine

Detailed Description

The drug being tested in this study is called vortioxetine (Lu AA21004). Vortioxetine is being tested in Japanese healthy adult participants. This study will look at the bioequivalence of a single oral administration of a vortioxetine 20 mg tablet in comparison with two of vortioxetine 10 mg tablets, and also look at the safety of a single oral dose of vortioxetine 20 mg in Japanese healthy adult participants.

The study will enroll 28 (14 for each sequence) healthy participants. In case bioequivalence cannot be demonstrated with the number of participants initially planned, an add-on participant study may be conducted (as a maximum 28 participants additionally). Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups.

• Treatment Group A: Vortioxetine 20 mg (one 20 mg tablet) in Period 1 + Vortioxetine 20 mg (two 10 mg tablets) in Period 2
• Treatment Group B: Vortioxetine 20 mg (two 10 mg tablets) in Period 1 + Vortioxetine 20 mg (one 20 mg tablet) in Period 2

This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 25 days. Participants will make two visits to the clinic and be hospitalized for ten days in total.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan
    • Nishi Kumamoto Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be a healthy Japanese adult volunteer.
2. Understand the contents of the study and is capable of providing written consent to participate in the study.
3. Be willing to comply with all study procedures and restrictions.
4. Aged between ≥20 and ≤45 years at the time of screening.
5. Have a BMI of ≥18.5 and ≤24.9 (kg/m^2) and a body weight of ≥50 kg at the time of screening.
6. Be a extensive metabolizer (EM) based on CYP2D6 genotyping at the time of screening.
7. A female participant of childbearing potential with a non-sterilized male partner must agree to routinely use appropriate contraception during the study from the time of signing informed consent until 4 weeks after last dosing of the study drug.

Exclusion Criteria:

1. Has received any investigational drug within 90 days before screening for this study.
2. Previously received Lu AA21004 before participation in this study.
3. Is an employee of the sponsor or the study site, or immediate family member, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or who may be coerced to provide consent.
4. Has uncontrolled, clinically relevant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may affect study participation or study results.
5. Has a history of multiple episodes or severe allergies (eg, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription drugs, over the counter (OTC) drugs, or foods.
6. Has a positive pregnancy test at the time of screening or Day -1.
7. Is a pregnant or lactating female.
8. Has a positive urine drug screen test at the time of screening or Day -1.
9. Has a history of drug abuse (defined as any illicit drug use) or has a history of alcohol dependence within 2 years before the start of screening or is unwilling to agree to abstain from alcohol and drugs throughout the study.
10. Consumes 6 or more servings of caffeinated beverages (containing about 120 mg of caffeine per serving) such as of coffee, tea, cola, or energy drinks.
11. Is a smoker who smoked cigarettes or used nicotine-containing products (such as nicotine patch) within 6 months before the Period 1 study drug administration.
12. Used any of the excluded drugs, dietary products or foods during the specified time periods, or will need any of them during the study period.
13. Has any current or recent gastrointestinal diseases that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn), or any surgical intervention (Stomach, cholecystectomy etc.).
14. Has a history of cancer.
15. Has a positive test result for any of the following at the time of screening: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, serological test for syphilis.
16. Has poor peripheral venous access.
17. Has undergone whole blood collection of at least 200 mL within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of Period 1 study drug administration.
18. Has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of Period 1 study drug administration.
19. Has undergone blood component collection within 2 weeks (14 days) prior to the start of Period 1 study drug administration.
20. Has any clinically relevant abnormality in vital signs or 12-lead electrocardiograms (ECG) at screening or on Day -1 of Period 1.
21. Has abnormal laboratory test values at screening or on Day -1 of Period 1 indicating clinically relevant underlying disease, or showing alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5×upper limit of normal (ULN).
22. Is unlikely to comply with the protocol requirements or is unsuitable as a participant of this study for any other reason in the opinion of the investigator or sub-investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vortioxetine one 20 mg tablet + two 10 mg tablets; Vortioxetine 20 mg (one 20 mg tablet) on Day 1 in Period 1 in a fasted state + vortioxetine 20 mg (two 10 mg tablets) on Day 1 in Period 2 in a fasted state.	Drug: Vortioxetine; Vortioxetine tablet; Other Names: Lu AA21004
Experimental: Vortioxetine two 10 mg tablets + one 20 mg tablet; Vortioxetine 20 mg (two 10 mg tablets) on Day 1 in Period 1 in a fasted state + vortioxetine 20 mg (one 20 mg tablet) on Day 1 in Period 2 in a fasted state.	Drug: Vortioxetine; Vortioxetine tablet; Other Names: Lu AA21004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Time Point of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Cmax: Maximum Plasma Concentration (Observed Value) of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Tmax: Time to Reach Cmax (Observed Value) of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
MRT∞, ev: Mean Residence Time 0 to Infinity of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
MRTlast, ev: Mean Residence Time From Time 0 to the Time of the Last Quantifiable Concentration of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
λz: Apparent Elimination Rate Constant of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
T1/2z: Apparent Elimination Half-Life of Unchanged Lu AA21004	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)	Up to Day 25
Number of Participants With TEAE Related to Vital Sign	Up to Day 25
Number of Participants With TEAE Related to Clinical Laboratory Tests (Alanine Aminotransferase Increased)	Up to Day 25
Number of Participants With TEAE Related to 12-lead Electrocardiograms	Up to Day 25

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): April 13, 2018
• Study Completion (Actual): April 13, 2018

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 13, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine
• Other Study ID Numbers: Vortioxetine-1001; U1111-1208-2715 (Other Identifier: WHO); JapicCTI-183863 (Registry Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

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