Trial Outcomes & Findings for A Bioequivalence Study of the Lu AA21004 20 mg and 2×10 mg Tablets (NCT NCT03437564)

NCT ID: NCT03437564

Last Updated: 2019-06-27

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 28 participants
• Primary outcome timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
• Results posted on: 2019-06-27

Participant Flow

Participants took part in the study at 1 investigative site in Japan, from 16 February 2018 to 13 April 2018.

Healthy participants were enrolled in one of two treatment group (vortioxetine 20 mg (1×20 mg tablet) on Day 1 in Period 1, followed by vortioxetine 20 mg (2×10 mg tablets) on Day 1 in Period 2; vortioxetine 20 mg (2×10 mg tablets) on Day 1 in Period 1, followed by vortioxetine 20 mg (1×20 mg tablet) on Day 1 in Period 2) with cross over design.

Participant milestones

Measure	Vortioxetine One 20 mg Tablet + Two 10 mg Tablets Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state + vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets + One 20 mg Tablet Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state + vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 2 in a fasted state.
Overall Study STARTED	14	14
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Vortioxetine One 20 mg Tablet + Two 10 mg Tablets n=14 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state + vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets + One 20 mg Table n=14 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state + vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 2 in a fasted state.	Total n=28 Participants Total of all reporting groups
Age, Continuous	24.0 Years STANDARD_DEVIATION 6.52 • n=14 Participants	24.0 Years STANDARD_DEVIATION 4.96 • n=14 Participants	24.0 Years STANDARD_DEVIATION 5.68 • n=28 Participants
Sex: Female, Male Female	0 Participants n=14 Participants	0 Participants n=14 Participants	0 Participants n=28 Participants
Sex: Female, Male Male	14 Participants n=14 Participants	14 Participants n=14 Participants	28 Participants n=28 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Japan	14 Participants n=14 Participants	14 Participants n=14 Participants	28 Participants n=28 Participants
Height	172.4 Centimeters (cm) STANDARD_DEVIATION 3.94 • n=14 Participants	170.2 Centimeters (cm) STANDARD_DEVIATION 6.48 • n=14 Participants	171.3 Centimeters (cm) STANDARD_DEVIATION 5.38 • n=28 Participants
Weight	63.86 Kilograms (kg) STANDARD_DEVIATION 6.694 • n=14 Participants	61.91 Kilograms (kg) STANDARD_DEVIATION 6.254 • n=14 Participants	62.89 Kilograms (kg) STANDARD_DEVIATION 6.434 • n=28 Participants
BMI	21.46 kg/meter (m)^2 STANDARD_DEVIATION 1.812 • n=14 Participants	21.33 kg/meter (m)^2 STANDARD_DEVIATION 1.175 • n=14 Participants	21.39 kg/meter (m)^2 STANDARD_DEVIATION 1.500 • n=28 Participants
Smoking Classification Never Smoked	12 Participants n=14 Participants	13 Participants n=14 Participants	25 Participants n=28 Participants
Smoking Classification Ex-Smoker	2 Participants n=14 Participants	1 Participants n=14 Participants	3 Participants n=28 Participants
Alcohol Classification Drank 2 to 3 Days a Week	3 Participants n=14 Participants	0 Participants n=14 Participants	3 Participants n=28 Participants
Alcohol Classification Drank 2 to 3 Days a Month	9 Participants n=14 Participants	8 Participants n=14 Participants	17 Participants n=28 Participants
Alcohol Classification Never Drank	2 Participants n=14 Participants	6 Participants n=14 Participants	8 Participants n=28 Participants
Caffeine Classification Had Caffeine Consumption	5 Participants n=14 Participants	4 Participants n=14 Participants	9 Participants n=28 Participants
Caffeine Classification Had no Caffeine Consumption	9 Participants n=14 Participants	10 Participants n=14 Participants	19 Participants n=28 Participants

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Time Point of Unchanged Lu AA21004	299.3 hour*nanogram per milliliter (h*ng/mL) Standard Deviation 59.820	301.1 hour*nanogram per milliliter (h*ng/mL) Standard Deviation 62.070

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Cmax: Maximum Plasma Concentration (Observed Value) of Unchanged Lu AA21004	8.744 ng/mL Standard Deviation 1.7838	8.976 ng/mL Standard Deviation 1.6936

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Unchanged Lu AA21004	463.9 h*ng/mL Standard Deviation 135.58	477.6 h*ng/mL Standard Deviation 164.83

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Tmax: Time to Reach Cmax (Observed Value) of Unchanged Lu AA21004	6.000 Hours Interval 6.0 to 8.0	6.000 Hours Interval 6.0 to 8.0

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
MRT∞, ev: Mean Residence Time 0 to Infinity of Unchanged Lu AA21004	67.27 Hours Standard Deviation 14.145	68.84 Hours Standard Deviation 18.646

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
MRTlast, ev: Mean Residence Time From Time 0 to the Time of the Last Quantifiable Concentration of Unchanged Lu AA21004	30.12 Hours Standard Deviation 1.8274	30.12 Hours Standard Deviation 1.8335

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
λz: Apparent Elimination Rate Constant of Unchanged Lu AA21004	0.01608 1/Hours Standard Deviation 0.0040090	0.01599 1/Hours Standard Deviation 0.0041766

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Analysis Set; PK analysis set included all treated participants who had no major protocol violations, completed the minimum element of the protocol, and had evaluable pharmacokinetic data.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
T1/2z: Apparent Elimination Half-Life of Unchanged Lu AA21004	45.36 Hours Standard Deviation 9.7694	46.44 Hours Standard Deviation 13.090

SECONDARY outcome

Timeframe: Up to Day 25

Population: Safety Analysis Set; The safety analysis set included all participants who received at least one dose of the study drug.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 25

Population: Safety Analysis Set; The safety analysis set included all participants who received at least one dose of the study drug.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Number of Participants With TEAE Related to Vital Sign	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 25

Population: Safety Analysis Set; The safety analysis set included all participants who received at least one dose of the study drug.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Number of Participants With TEAE Related to Clinical Laboratory Tests (Alanine Aminotransferase Increased)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 25

Population: Safety Analysis Set; The safety analysis set included all participants who received at least one dose of the study drug.

Outcome measures

Measure	Vortioxetine One 20 mg Tablet n=28 Participants Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 Participants Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Number of Participants With TEAE Related to 12-lead Electrocardiograms	0 Participants	0 Participants

Adverse Events

Vortioxetine One 20 mg Tablet

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Vortioxetine Two 10 mg Tablets

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vortioxetine One 20 mg Tablet n=28 participants at risk Vortioxetine 20 mg (one 20 mg tablet) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.	Vortioxetine Two 10 mg Tablets n=28 participants at risk Vortioxetine 20 mg (two 10 mg tablets) orally, once on Day 1 in Period 1 in a fasted state plus Day 1 in Period 2 in a fasted state.
Investigations Alanine aminotransferase increased	3.6% 1/28 • Up to Day 25 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/28 • Up to Day 25 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER