Trial Outcomes & Findings for Pharmacokinetics, Safety and Tolerability of Vortioxetine in Normal Hepatic Function or Severe Hepatic Impairment (NCT NCT02170220)

NCT ID: NCT02170220

Last Updated: 2016-01-05

Results Overview

(AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC\[0-tlqc\]).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose
• Results posted on: 2016-01-05

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 09 July 2014 (first participant signed the informed consent form) to 01 December 2014.

Participants with normal hepatic function and participants with severe hepatic impairment received a single dose of 5 mg vortioxetine.

Participant milestones

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics, Safety and Tolerability of Vortioxetine in Normal Hepatic Function or Severe Hepatic Impairment

Baseline characteristics by cohort

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.	Total n=12 Participants Total of all reporting groups
Age, Continuous	50.3 years STANDARD_DEVIATION 2.58 • n=5 Participants	54.8 years STANDARD_DEVIATION 6.79 • n=7 Participants	52.6 years STANDARD_DEVIATION 5.43 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized White	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Height	169.3 cm STANDARD_DEVIATION 10.31 • n=5 Participants	165.7 cm STANDARD_DEVIATION 10.41 • n=7 Participants	167.5 cm STANDARD_DEVIATION 10.06 • n=5 Participants
Weight	80.65 kg STANDARD_DEVIATION 13.261 • n=5 Participants	82.17 kg STANDARD_DEVIATION 29.038 • n=7 Participants	81.41 kg STANDARD_DEVIATION 21.537 • n=5 Participants
Body Mass Index (BMI)	28.02 kg/m^2 STANDARD_DEVIATION 2.927 • n=5 Participants	29.43 kg/m^2 STANDARD_DEVIATION 7.554 • n=7 Participants	28.73 kg/m^2 STANDARD_DEVIATION 5.512 • n=5 Participants
Smoking Classification Never smoked	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Smoking Classification Current smoker	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Smoking Classification Ex-smoker	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Alcohol Classification Never drank	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Alcohol Classification Current drinker	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Alcohol Classification Ex-drinker	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Caffeine Consumption Yes	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Caffeine Consumption No	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: Pharmacokinetic (PK) Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

(AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC[0-tlqc]).

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vortioxetine	166.955 ng*hr/mL Standard Deviation 45.1656	188.663 ng*hr/mL Standard Deviation 68.5380

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

(AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC[0-tlqc]).

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vortioxetine Metabolite Lu AA34443	88.614 ng*hr/mL Standard Deviation 53.1478	71.942 ng*hr/mL Standard Deviation 48.9356

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

(AUC(0-tlqc) is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC[0-tlqc]).

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vortioxetine Metabolite Lu AA39835	1.143 ng*hr/mL Standard Deviation 1.2640	0.078 ng*hr/mL Standard Deviation 0.1903

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Vortioxetine	187.202 ng*hr/mL Standard Deviation 52.8692	288.053 ng*hr/mL Standard Deviation 148.7612

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=5 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=5 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Vortioxetine Metabolite Lu AA34443	122.899 ng*hr/mL Standard Deviation 39.2417	124.708 ng*hr/mL Standard Deviation 46.8665

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
Cmax: Maximum Observed Plasma Concentration for Vortioxetine	2.078 ng/mL Standard Deviation 0.4675	1.670 ng/mL Standard Deviation 0.6135

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
Cmax: Maximum Observed Plasma Concentration for Vortioxetine Metabolite Lu AA34443	2.654 ng/mL Standard Deviation 1.6018	1.374 ng/mL Standard Deviation 0.7849

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
Cmax: Maximum Observed Plasma Concentration for Vortioxetine Metabolite Lu AA39835	0.029 ng/mL Standard Deviation 0.0324	0.008 ng/mL Standard Deviation 0.0190

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

AUC(0-tlqc)u is a measure of total unbound plasma exposure to the drug from time 0 to time of the last quantifiable concentration (AUC[0-tlqc]u).

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-tlqc)u: Area Under the Unbound Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vortioxetine	1.611 ng*hr/mL Standard Deviation 0.4937	1.653 ng*hr/mL Standard Deviation 0.6882

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

AUC(0-inf)u is a measure of total unbound plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
AUC(0-inf)u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Vortioxetine	1.806 ng*hr/mL Standard Deviation 0.5685	2.558 ng*hr/mL Standard Deviation 1.5242

PRIMARY outcome

Timeframe: Predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 240 hours postdose

Population: PK Analysis Set included all enrolled participants who received at least 1 dose of study drug with at least 1 measureable plasma concentration.

Maximum Observed Unbound Plasma Concentration (Cmaxu) is the peak unbound plasma concentration of a drug after administration, obtained directly from the unbound plasma concentration-time curve.

Outcome measures

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 Participants Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
Cmaxu: Maximum Observed Unbound Plasma Concentration for Vortioxetine	0.020 ng/mL Standard Deviation 0.0056	0.014 ng/mL Standard Deviation 0.0053

Adverse Events

Vortioxetine 5 mg: Normal Hepatic Function Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vortioxetine 5 mg: Severe Hepatic Impairment Cohort

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vortioxetine 5 mg: Normal Hepatic Function Cohort n=6 participants at risk Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.	Vortioxetine 5 mg: Severe Hepatic Impairment Cohort n=6 participants at risk Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.
Gastrointestinal disorders Vomiting	0.00% 0/6 • The first dose of study drug to within 32 days 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.	16.7% 1/6 • The first dose of study drug to within 32 days 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.
Investigations Blood potassium increased	0.00% 0/6 • The first dose of study drug to within 32 days 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.	16.7% 1/6 • The first dose of study drug to within 32 days 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, Clinical Science

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER