Healthy
Conditions
Keywords
Drug Therapy, pharmacodynamic
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.
Detailed description
This study will look at an investigational medicine called vortioxetine to see how the drug affects the body and how the body handles the drug. The study enrolled 17 patients. Participants were randomly assigned at a 2:1 ratio to one of the following two treatment groups-which remained undisclosed to both the participant and study doctor during the study (unless there was an urgent medical need): * Vortioxetine 20 mg * Placebo (dummy inactive pill) - this was a capsule that looked like the study drug but had no active ingredient. All participants were asked to take one capsule at the same time each day throughout the study. This single-center trial was conducted in the United States. The overall time to participate in this study was approximately 7 weeks. Participants made 2 visits to the clinic, including 18 days confinement to the clinic, and were contacted by telephone 1 day and 27 days after leaving confinement for a follow-up assessment.
Interventions
DRUGVortioxetine
Encapsulated tablet
DRUGPlacebo
Vortioxetine placebo-matching capsules.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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. * Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody at Screening or a known history of human immunodeficiency virus infection. * Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -2) or is unwilling to abstain from these products for the duration of the study. * Cotinine test is positive at Screening or Check-in (Day 2). * Has poor peripheral venous access. * Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1. * Has a Screening or Check-in (Day -2) abnormal (clinically significant) electrocardiogram (ECG). Entry of any patient with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator. * Has abnormal Screening or Day -2 laboratory values that suggest a clinically significant underlying disease or with the following lab abnormalities: alanine aminotransferase and/or aspartate aminotransferase \>1.5 times the upper limit of normal. * Has had cerebrospinal fluid (CSF) collection performed within 30 days prior to Check-in (Day -2). * Has taken any selective serotonin reuptake inhibitor (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors, antipsychotics, tricyclic antidepressants, or mood stabilizers within the last year prior to Screening. * Has a known hypersensitivity to the anesthetic or its derivatives used during CSF collection, or any medication used to prepare the area of lumbar puncture. * Has significant vertebral deformities (scoliosis or kyphosis) which, in the opinion of the investigator, may interfere with lumbar puncture procedure. * Has a history of clinically significant back pain and/or injury. * Has local infection at the puncture site. * Has a history of significant bleeding or coagulation disorder and/or low platelet levels (\<130x10\^9/L) or increased international normalized ratio (INR) (\>1.3) at Screening. * Answers positive to any suicidal ideation and/or suicidal behavior questions during administration of the Columbia-Suicide Severity Rating Scale. * Has an orthostatic blood pressure drop of ≥20 mm Hg (based on the drop between supine and standing \[3 minutes\] systolic blood pressure) at Screening or Check-in (Day -2). * Has abnormal Screening or Day -2 vital signs: resting systolic blood pressure ≤90 or ≥140 mm Hg or a resting diastolic blood pressure ≤50 or ≥90 mm Hg in supine position; resting pulse or heart rate (as read on ECG) \<45 bpm or \>100 bpm. No more than 2 repeat measurements. * Exercises extensively in his normal life (e.g., marathon running, triathlon, physical sports at a contest level etc).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | 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. | 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). |
| Maximum Concentration of 5-HT in Plasma | 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. | 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). |
| Time to Maximum Concentration of 5-HT in Plasma | 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. | 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). |
| Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | 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. | 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). |
| Maximum Concentration of 5-HT in Cerobrospinal Fluid | 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. | 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). |
| Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day -1, Day 1 and Day 14. CSF samples were taken predose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose. | 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). |
| Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxyindoleacetic Acid (5-HIAA) in Plasma | 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-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. |
| Maximum Concentration of 5-HIAA in Plasma | 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. | 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 |
| Time to Maximum Concentration of 5-HIAA in Plasma | Day 1 and Day 14. Blood samples were taken predose and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose. | 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. |
| Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | 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. | 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). |
| Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | 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. | 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). |
| Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | 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. | 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). |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at one investigative site in the United States from 14 March 2011 to 11 June 2011.
Pre-assignment details
In this study, 17 healthy men were enrolled and randomized to receive an oral dose of vortioxetine 20 mg or placebo in a 2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Vortioxetine Vortioxetine 20 mg, encapsulated tablet, orally, once daily for up to 14 days. | 12 |
| Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 14 days. | 5 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | Vortioxetine | Total | Placebo |
|---|---|---|---|
| Age Continuous | 34.3 years STANDARD_DEVIATION 11.19 | 34.4 years STANDARD_DEVIATION 10.71 | 34.8 years STANDARD_DEVIATION 10.71 |
| Body Mass Index (BMI) | 26.2 kg/m^2 STANDARD_DEVIATION 2.85 | 26.1 kg/m^2 STANDARD_DEVIATION 2.56 | 25.8 kg/m^2 STANDARD_DEVIATION 1.92 |
| Caffeine consumption Consumes 0-5 cups daily | 12 participants | 17 participants | 5 participants |
| Caffeine consumption Consumes >5 cups daily | 0 participants | 0 participants | 0 participants |
| Current nicotine user No | 12 participants | 17 participants | 5 participants |
| Current nicotine user Yes | 0 participants | 0 participants | 0 participants |
| Drinking habits Drinks 0-14/week | 12 participants | 17 participants | 5 participants |
| Drinking habits Drinks >14/week | 0 participants | 0 participants | 0 participants |
| Former nicotine user No | 11 participants | 15 participants | 4 participants |
| Former nicotine user Yes | 1 participants | 2 participants | 1 participants |
| Height | 176.8 cm STANDARD_DEVIATION 5.88 | 176.6 cm STANDARD_DEVIATION 6.37 | 175.9 cm STANDARD_DEVIATION 8.15 |
| Race/Ethnicity, Customized Black or African American | 3 participants | 4 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 9 participants | 14 participants | 5 participants |
| Race/Ethnicity, Customized White | 9 participants | 13 participants | 4 participants |
| Region of Enrollment United States | 12 participants | 17 participants | 5 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 17 Participants | 5 Participants |
| Weight | 81.8 kg STANDARD_DEVIATION 8.84 | 81.3 kg STANDARD_DEVIATION 8.29 | 79.9 kg STANDARD_DEVIATION 7.52 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 4 / 5 |
| serious Total, serious adverse events | 0 / 12 | 0 / 5 |
Outcome results
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | Day -1 (n=12, 5) | 620.61 ng*hr/mL | Standard Deviation 182.391 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | Day 1 (n=12, 5) | 636.14 ng*hr/mL | Standard Deviation 246.071 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | Day 14 (n=9, 5) | 429.23 ng*hr/mL | Standard Deviation 99.575 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | Day 1 (n=12, 5) | 774.95 ng*hr/mL | Standard Deviation 319.86 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | Day -1 (n=12, 5) | 718.14 ng*hr/mL | Standard Deviation 247.082 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HIAA in Cerebrospinal Fluid | Day 14 (n=9, 5) | 644.24 ng*hr/mL | Standard Deviation 206.121 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | Day -1 (n=11, 5) | 987.71 pg*hr/mL | Standard Deviation 1898.943 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | Day 1 (n=11, 5) | 627.78 pg*hr/mL | Standard Deviation 164.679 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | Day 14 (n=9, 5) | 1165.73 pg*hr/mL | Standard Deviation 290.389 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | Day -1 (n=11, 5) | 509.77 pg*hr/mL | Standard Deviation 199.658 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | Day 1 (n=11, 5) | 497.40 pg*hr/mL | Standard Deviation 302.72 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-HT in Cerebrospinal Fluid | Day 14 (n=9, 5) | 444.88 pg*hr/mL | Standard Deviation 24.908 |
Primary
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.
Time frame: Day 1 and Day 14. Blood samples were taken predose and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxyindoleacetic Acid (5-HIAA) in Plasma | Day 1 (n=12, 5) | 140.01 ng*hr/mL | Standard Deviation 23.633 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxyindoleacetic Acid (5-HIAA) in Plasma | Day 14 (n=10, 5) | 143.69 ng*hr/mL | Standard Deviation 30.049 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxyindoleacetic Acid (5-HIAA) in Plasma | Day 1 (n=12, 5) | 145.92 ng*hr/mL | Standard Deviation 28.844 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxyindoleacetic Acid (5-HIAA) in Plasma | Day 14 (n=10, 5) | 140.40 ng*hr/mL | Standard Deviation 25.305 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | Day -1 (n=10, 4) | 4183024 pg*hr/mL | Standard Deviation 1362135 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | Day 1 (n=6, 4) | 4224058 pg*hr/mL | Standard Deviation 2028835 |
| Vortioxetine | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | Day 14 (n=9, 5) | 1718863 pg*hr/mL | Standard Deviation 530633 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | Day -1 (n=10, 4) | 3854399 pg*hr/mL | Standard Deviation 1728230 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | Day 1 (n=6, 4) | 3912292 pg*hr/mL | Standard Deviation 2083773 |
| Placebo | Area Under the Effect Curve From Time Zero to 24 Hours Postdose of 5-hydroxytryptamine (5-HT) in Plasma | Day 14 (n=9, 5) | 3858350 pg*hr/mL | Standard Deviation 2212719 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day -1 (n=12, 5) | 29.87 ng/mL | Standard Deviation 8.231 |
| Vortioxetine | Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 1 (n=12, 5) | 31.13 ng/mL | Standard Deviation 9.567 |
| Vortioxetine | Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 14 (n=9, 5) | 20.18 ng/mL | Standard Deviation 4.935 |
| Placebo | Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day -1 (n=12, 5) | 34.30 ng/mL | Standard Deviation 12.27 |
| Placebo | Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 1 (n=12, 5) | 36.98 ng/mL | Standard Deviation 18.346 |
| Placebo | Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 14 (n=9, 5) | 30.16 ng/mL | Standard Deviation 8.768 |
Primary
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
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Maximum Concentration of 5-HIAA in Plasma | Day 1 (n=12, 5) | 7.25 ng/mL | Standard Deviation 1.113 |
| Vortioxetine | Maximum Concentration of 5-HIAA in Plasma | Day 14 (n=10, 5) | 6.90 ng/mL | Standard Deviation 1.402 |
| Placebo | Maximum Concentration of 5-HIAA in Plasma | Day 1 (n=12, 5) | 6.97 ng/mL | Standard Deviation 1.282 |
| Placebo | Maximum Concentration of 5-HIAA in Plasma | Day 14 (n=10, 5) | 7.10 ng/mL | Standard Deviation 1.301 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Maximum Concentration of 5-HT in Cerobrospinal Fluid | Day -1 (n=11, 5) | 116.60 pg/mL | Standard Deviation 293.721 |
| Vortioxetine | Maximum Concentration of 5-HT in Cerobrospinal Fluid | Day 1 (n=11, 5) | 35.46 pg/mL | Standard Deviation 13.172 |
| Vortioxetine | Maximum Concentration of 5-HT in Cerobrospinal Fluid | Day 14 (n=9, 5) | 59.80 pg/mL | Standard Deviation 16.524 |
| Placebo | Maximum Concentration of 5-HT in Cerobrospinal Fluid | Day -1 (n=11, 5) | 67.74 pg/mL | Standard Deviation 94.396 |
| Placebo | Maximum Concentration of 5-HT in Cerobrospinal Fluid | Day 1 (n=11, 5) | 24.10 pg/mL | Standard Deviation 14.03 |
| Placebo | Maximum Concentration of 5-HT in Cerobrospinal Fluid | Day 14 (n=9, 5) | 51.46 pg/mL | Standard Deviation 33.647 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Maximum Concentration of 5-HT in Plasma | Day -1 (n=10, 4) | 273800 pg/mL | Standard Deviation 111197 |
| Vortioxetine | Maximum Concentration of 5-HT in Plasma | Day 1 (n=6, 4) | 247667 pg/mL | Standard Deviation 136695 |
| Vortioxetine | Maximum Concentration of 5-HT in Plasma | Day 14 (n=9, 5) | 94233.3 pg/mL | Standard Deviation 40258.4 |
| Placebo | Maximum Concentration of 5-HT in Plasma | Day -1 (n=10, 4) | 231500 pg/mL | Standard Deviation 98083.3 |
| Placebo | Maximum Concentration of 5-HT in Plasma | Day 1 (n=6, 4) | 251250 pg/mL | Standard Deviation 63615.4 |
| Placebo | Maximum Concentration of 5-HT in Plasma | Day 14 (n=9, 5) | 242200 pg/mL | Standard Deviation 115103 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 14 (n=9, 5) | 11.70 hours | Standard Deviation 10.576 |
| Vortioxetine | Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day -1 (n=12, 5) | 14.16 hours | Standard Deviation 10.71 |
| Vortioxetine | Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 1 (n=12, 5) | 6.24 hours | Standard Deviation 8.96 |
| Placebo | Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 14 (n=9, 5) | 9.90 hours | Standard Deviation 9.592 |
| Placebo | Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day -1 (n=12, 5) | 19.78 hours | Standard Deviation 8.877 |
| Placebo | Time to Maximum Concentration of 5-HIAA in Cerebrospinal Fluid | Day 1 (n=12, 5) | 19.00 hours | Standard Deviation 10.621 |
Primary
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.
Time frame: Day 1 and Day 14. Blood samples were taken predose and at 1, 2, 4, 8, 12, 16 and 24 hours post-dose.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Time to Maximum Concentration of 5-HIAA in Plasma | Day 1 (n=12, 5) | 13.02 hours | Standard Deviation 10.992 |
| Vortioxetine | Time to Maximum Concentration of 5-HIAA in Plasma | Day 14 (n=10, 5) | 16.80 hours | Standard Deviation 7.005 |
| Placebo | Time to Maximum Concentration of 5-HIAA in Plasma | Day 1 (n=12, 5) | 15.13 hours | Standard Deviation 9.886 |
| Placebo | Time to Maximum Concentration of 5-HIAA in Plasma | Day 14 (n=10, 5) | 18.40 hours | Standard Deviation 5.367 |
Primary
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).
Time frame: Day -1, Day 1 and Day 14. CSF samples were taken predose and at 1, 2, 4, 8, 12, 16, and 24 hours postdose.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day -1 (n=11, 5) | 4.30 hours | Standard Deviation 5.89 |
| Vortioxetine | Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day 1 (n=11, 5) | 17.32 hours | Standard Deviation 7.177 |
| Vortioxetine | Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day 14 (n=9, 5) | 3.02 hours | Standard Deviation 3.576 |
| Placebo | Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day -1 (n=11, 5) | 7.13 hours | Standard Deviation 10.624 |
| Placebo | Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day 1 (n=11, 5) | 6.92 hours | Standard Deviation 8.225 |
| Placebo | Time to Maximum Concentration of 5-HT in Cerebrospinal Fluid | Day 14 (n=9, 5) | 4.94 hours | Standard Deviation 6.964 |
Primary
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).
Time frame: 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.
Population: The pharmacodynamic (PD) set consisted of all participants in the safety set with sufficient plasma or serum or CSF data for derivation of at least 1 PD parameter. If a patient's concentration profile contained ≤3 data points, the PD parameter results were not included. n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Time to Maximum Concentration of 5-HT in Plasma | Day -1 (n=10, 4) | 12.65 hours | Standard Deviation 9.409 |
| Vortioxetine | Time to Maximum Concentration of 5-HT in Plasma | Day 1 (n=6, 4) | 4.86 hours | Standard Deviation 7.253 |
| Vortioxetine | Time to Maximum Concentration of 5-HT in Plasma | Day 14 (n=9, 5) | 9.11 hours | Standard Deviation 10.08 |
| Placebo | Time to Maximum Concentration of 5-HT in Plasma | Day -1 (n=10, 4) | 7.26 hours | Standard Deviation 7.984 |
| Placebo | Time to Maximum Concentration of 5-HT in Plasma | Day 1 (n=6, 4) | 14.42 hours | Standard Deviation 11.146 |
| Placebo | Time to Maximum Concentration of 5-HT in Plasma | Day 14 (n=9, 5) | 8.40 hours | Standard Deviation 6.986 |