Effects of Vortioxetine (Lu AA21004) on the Concentrations of Selected Neurotransmitters in Healthy Male Adults

NCT01299805 | Completed Phase 1 Results

• 2 other identifiers: LuAA21004_124U1111-1119-1680
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the pharmacodynamics (the drug's effect on the body), the pharmacokinetics (the body's handling of the drug), and the safety and tolerability of vortioxetine, once daily (QD) in healthy men.

Conditions

Healthy

Keywords

Drug Therapy; pharmacodynamic

Outcome Measures

Primary Outcomes (12)

• Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma

  The area under the effect-time curve from time 0 to 24 hours postdose (AUEC\[0-24\]) of the neurotransmitter 5-HT (serotonin) in plasma was measured at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. Blood samples were taken predose (up to 15 minutes prior) and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.

• Maximum Concentration of 5-HT in Plasma

  The maximum observed effect (Emax), assessed by the maximum observed concentration of 5-HT in plasma measured at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. Blood samples were taken predose (up to 15 minutes prior) and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.

• Time to Maximum Concentration of 5-HT in Plasma

  The time to reach maximum pharmacodynamic effect (Emax) was assessed by the time to maximum concentration of 5-HT in plasma at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. Blood samples were taken predose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

• Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid

  The area under the effect-time curve from time 0 to 24 hours postdose (AUEC\[0-24\]) of 5-hydroxytryptamine (5-HT) in cerebrospinal fluid (CSF) was measured at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. CSF samples were taken prior to dose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

• Maximum Concentration of 5-HT in Cerobrospinal Fluid

  The maximum observed effect (Emax), assessed by the maximum concentration of 5-HT in cerebrospinal fluid (CSF) measured at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. CSF samples were taken prior to dose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

• Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid

  The time to reach maximum pharmacodynamic effect (Emax) was assessed by the time to maximum concentration of 5-HT in cerebrospinal fluid (CSF) at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1, Day 1 and Day 14. CSF samples were taken predose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

• Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxyindoleacetic Acid (5-HIAA) in Plasma

  Area under the effect-time curve from time 0 to 24 hours postdose (AUEC\[0-24\]) of 5-HIAA, a metabolite of the neurotransmitter serotonin, in plasma was measured after a single dose (Day 1) and after multiple doses (Day 14). Note: Plasma samples for 5-HIAA on Day -1 were lost in shipping. Therefore, no PD parameters were calculated for Day -1.

  Day 1 and Day 14. Blood samples were taken predose and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.

• Maximum Concentration of 5-HIAA in Plasma

  The maximum observed effect (Emax), assessed by the maximum observed concentration of 5-HIAA in plasma measured after a single dose (Day 1) and after multiple doses (Day 14). Note: Plasma samples for 5-HIAA on Day -1 were lost in shipping. Therefore, no PD parameters were calculated for Day -1

  Day 1 and Day 14. Blood samples were taken predose (up to 15 minutes prior) and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.

• Time to Maximum Concentration of 5-HIAA in Plasma

  The time to reach maximum pharmacodynamic effect (Emax) was assessed by the time to maximum concentration of 5-hydroxyindoleacetic acid (5-HIAA) in plasma after a single dose (Day 1) and after multiple doses (Day 14). Note: Plasma samples for 5-HIAA on Day -1 were lost in shipping. Therefore, no PD parameters were calculated for Day -1.

  Day 1 and Day 14. Blood samples were taken predose and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.

• Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid

  The area under the effect-time curve from time 0 to 24 hours postdose (AUEC\[0-24\]) of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) was measured at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. CSF samples were taken prior to dose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

• Maximum Concentration of 5-HIAA in Cerebrospinal Fluid

  The maximum observed effect (Emax), assessed by the maximum observed concentration of 5-HIAA in cerebrospinal fluid (CSF) measured at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1 (Baseline), Day 1 and Day 14. CSF samples were taken prior to dose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

• Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid

  The time to reach maximum pharmacodynamic effect (Emax) was assessed by the time to maximum concentration of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) at Baseline, after a single dose (Day 1) and after multiple doses (Day 14).

  Day -1, Day 1 and Day 14. CSF samples were taken prior to dose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.

Study Arms (2)

Vortioxetine

EXPERIMENTAL

Vortioxetine 20 mg, encapsulated tablet, orally, once daily for up to 14 days.

Drug: Vortioxetine

Placebo

PLACEBO COMPARATOR

Vortioxetine placebo-matching capsules, orally, once daily for up to 14 days.

Drug: Placebo

Interventions

Vortioxetine DRUG

Encapsulated tablet

Also known as: Lu AA21004, Brintellix

Vortioxetine

Placebo DRUG

Vortioxetine placebo-matching capsules.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Weighs at least 50 kg and has a body mass index between 19.0 and 32.0 kg/m\^2, inclusive at Screening.
• Males who are nonsterilized and sexually active with a female partner of childbearing potential must agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 6 weeks after last dose of study medication. The acceptable method of contraception is defined as one that has no higher than a 1% failure rate.

You may not qualify if:

• Received any investigational compound within 45 days prior to Check-in (Day -2).
• Received Lu AA21004 in previous clinical study or as therapeutic agent.
• History of or uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, central nervous system, hepatic hematopoietic disease, renal metabolic, gastrointestinal, or endocrine disease, serious allergy, asthma, hypoxemia, hypertension, seizures, allergic skin rash or other abnormality, which may impact the ability of the participant to participate or potentially confound study results.
• Participant has 1 or more of the following:
• Any current psychiatric disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR).
• Current or history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
• Presence or history of a clinically significant neurological disorder (including epilepsy).
• Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
• Any Axis II disorder.
• Has a known hypersensitivity to any component of the formulation of Lu AA21004.
• Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -2).
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular consumption of 4 or more units per day) within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine.
• The participant intends to impregnate or donate sperm during the course of this study or for 6 weeks after last dose.
• Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (e.g., a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis; frequent (more than once per week) occurrence of heartburn, or any intra-abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy).
• 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 Day 1.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Glendale, California, 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

clinicaltrialregistry@tpna.com

800-778-2860

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: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2011
• First Posted: February 18, 2011
• Study Start: March 1, 2011
• Primary Completion: June 1, 2011
• Study Completion: July 1, 2011
• Last Updated: December 13, 2013
• Results First Posted: December 13, 2013

Record last verified: 2013-10

Locations

US (1)