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

NCT02170220 | Completed Phase 1 Results

• 2 other identifiers: LuAA21004_401U1111-1155-8776
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of vortioxetine and its metabolites Lu AA34443 and Lu AA39835 following a single oral dose administration of vortioxetine 5 mg in participants with severe hepatic impairment compared to healthy participants.

Conditions

Severe Hepatic Impairment

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (11)

• AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Vortioxetine

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

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

• 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

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

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

• 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

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

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

• AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Vortioxetine

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

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

• AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Vortioxetine Metabolite Lu AA34443

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

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

• Cmax: Maximum Observed Plasma Concentration for Vortioxetine

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

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

• Cmax: Maximum Observed Plasma Concentration for Vortioxetine Metabolite Lu AA34443

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

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

• Cmax: Maximum Observed Plasma Concentration for Vortioxetine Metabolite Lu AA39835

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

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

• 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

  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).

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

• AUC(0-inf)u: Area Under the Unbound Plasma Concentration-time Curve From Time 0 to Infinity for Vortioxetine

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

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

• Cmaxu: Maximum Observed Unbound Plasma Concentration for Vortioxetine

  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.

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

Study Arms (2)

Vortioxetine 5 mg: Normal Hepatic Function Cohort

EXPERIMENTAL

Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with normal hepatic function.

Drug: Vortioxetine

Vortioxetine 5 mg: Severe Hepatic Impairment Cohort

EXPERIMENTAL

Vortioxetine 5 mg, tablets, orally, once, on Day 1, in participants with severe hepatic impairment.

Drug: Vortioxetine

Interventions

Vortioxetine DRUG

Vortioxetine tablets

Also known as: Lu AA21004, BRINTELLIX

Vortioxetine 5 mg: Normal Hepatic Function Cohort; Vortioxetine 5 mg: Severe Hepatic Impairment Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General:
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is aged 18 to 75 years, inclusive, at the time of informed consent and first study medication dose.
• Weighs at least 50 kg and has a body mass index (BMI) between 19 and 38 kg/m\^2, inclusive at Screening.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose.
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
• Has a resting pulse and heart rate (as read on electrocardiogram \[ECG\]) between 51 and 100 beats per minutes (bpm), inclusive. For healthy participants in good physical condition and aged 18 to 45 years, inclusive, the lower limit is 45 bpm.
• Has a negative result at screening on the fecal occult blood screen.
• Healthy Participants (Normal Hepatic Function):
• The participant, in opinion of the investigator, is in good health as determined by a prestudy physical examination, medical history, vital signs, ECG, and the results of blood biochemistry, hematology, and serology tests, and urinalysis.
• Participants with severe hepatic impairment:
• Has been classified as having severe hepatic impairment as defined by the Child-Pugh classification system.
• Has case record notes demonstrating stable biochemistry as judged by the investigator prior to Screening.
• Has case record notes demonstrating physical signs consistent with a clinical diagnosis of liver impairment (eg, liver firmness to palpation, splenic enlargement, spider angiomas, palmar erythema, parotid hypertrophy, testicular atrophy, ascites, gynecomastia).

You may not qualify if:

• General:
• Has received any investigational compound within 45 days prior to first dose of study medication.
• Has received vortioxetine (Lu AA21004) in a previous clinical study or as a therapeutic agent.
• Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has received or donated more than 400 mL of blood or blood products within the 45 days preceding the beginning of the study or planned to donate blood during the study.
• Has a history of hypersensitivity or allergies to vortioxetine or related compounds with same mechanism of action including any associated excipients.
• Has a medical history of, or presence of, gastric or duodenal ulceration, gastritis, recent head injury or any other trauma within 1 week of Screening, extensive ecchymoses, hemoptysis, gingival bleeding, hematemesis, repeated or significant nose bleeds, periorbital hematoma, retinal detachment, menorrhagia, hematuria, or melena.
• Has had an acute, clinically significant illness within 30 days prior to the first dose of study medication.
• Has a history of abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy), thoracic, or nonperipheral vascular surgery within 6 months prior to the study medication.
• Has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to the first dose of study drug.
• Has taken any medications, supplements or food products except for those allowed for hepatically impaired participants, or approved by Takeda on a case-by-case basis.
• If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.
• If male, the participant intends to donate sperm during the course of this study or for 30 days thereafter.
• Has poor peripheral venous access.
• Has a serum creatinine level greater than 1.5 mg/dL at Screening or Day -1 (Check-in).

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

University of Miami

Miami, Florida, United States

Location

MeSH Terms

Interventions

Vortioxetine

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: June 23, 2014
• Study Start: July 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 5, 2016
• Results First Posted: January 5, 2016

Record last verified: 2015-12

Locations

US (1)