Clinical trial NCT03437564: A Bioequivalence Study of the Lu AA21004 20 mg and 2×10 mg Tablets
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Participants
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 28
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Time Point of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Cmax: Maximum Plasma Concentration (Observed Value) of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Secondary outcomes:
measure: AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Tmax: Time to Reach Cmax (Observed Value) of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: MRT∞, ev: Mean Residence Time 0 to Infinity of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: MRTlast, ev: Mean Residence Time From Time 0 to the Time of the Last Quantifiable Concentration of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: λz: Apparent Elimination Rate Constant of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: T1/2z: Apparent Elimination Half-Life of Unchanged Lu AA21004
timeFrame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
measure: Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to Day 25
measure: Number of Participants With TEAE Related to Vital Sign
timeFrame: Up to Day 25
measure: Number of Participants With TEAE Related to Clinical Laboratory Tests (Alanine Aminotransferase Increased)
timeFrame: Up to Day 25
measure: Number of Participants With TEAE Related to 12-lead Electrocardiograms
timeFrame: Up to Day 25
Other outcomes:
Locations:
city: Kumamoto
country: Japan
facility: Nishi Kumamoto Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: