Insomnia
Conditions
Keywords
Insomnia, primary insomnia, insomnia associated with psychiatric or physical disorder(s)
Brief summary
The purpose of this study is to investigate and evaluate the bioequivalence and food effect of SEP 190-102 in Japanese healthy subjects by assessing the pharmacokinetics parameters.
Interventions
DRUGEszopiclone 3 mg
Group A Period I, Group B Period II: Eszopiclone 3 mg tablet taken orally (po) with water as a single administration in the morning after fasting \>=10 hours. Except for the water taken with the drug, participants were not allowed any food/ drink from 10 hours before until 4 hours after administration of drug. Except for the water taken with the study drug, participants were not permitted to drink water from 1 hour before until 1 hour after administration of drug. Group B Period III: Eszopiclone 3 mg tablet taken po with water as a single administration in the morning 30 minutes after the start of breakfast. Except for the food/ drink at breakfast and the water taken with the study drug, participants were not allowed any food or drink from 10 hours before until 4 hours after administration of the drug. Except for the food/ drink at breakfast & the water taken with the study drug, participants were not permitted to drink water from 1 hour before until 1 hour after administration.
DRUGEszopiclone 1 mg
Group A Period II, Group B Period I: Eszopiclone three 1 mg tablets (total: 3 mg) taken orally with water as a single administration in the morning after fasting 10 or more hours. Except for the water taken with the study drug, participants were not allowed any food or drink (except water) from 10 hours before until 4 hours after administration of the study drug. Except for the water taken with the study drug, participants were not permitted to drink water from 1 hour before until 1 hour after administration of the study drug.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 54 Years
Healthy volunteers
Yes
Inclusion criteria
; 1. Participants who are given a full explanation about the objective and details of this study before starting screening and give written consent based on their free will 2. Japanese healthy male adult volunteers 3. Participants who are between 20 and 54 years of age at the time of obtaining written consent 4. Body Mass Index (BMI) is between 18.5 kg/m2 and 25.0 kg/m2 at the time of screening
Exclusion criteria
; 1. Participants with a present illness or history of allergy to drug or food, or seasonal allergy 2. Participants who have a known history of any gastrointestinal surgery (e.g., hepatectomy, nephrotomy, etc.) that may affect pharmacokinetic evaluation 3. Participants who are found to have clinically abnormal findings in medical history, symptoms and clinical findings, vital signs, electrocardiograms, or laboratory parameters of which require medical treatment(s), or impaired organ functions 4. Participants who have a known or suspected history of alcohol or drug abuse, or those who have a positive urine drug screening 5. Participants who are positive for hepatitis B surface antigen (HBs antigen), hepatitis C virus (HCV) antibody, or those who are human immunodeficiency virus (HIV)-positive, or those who are positive for syphilis screen 6. Participants who underwent blood transfusion within 12 weeks prior to, those whose 400 mL or more of whole blood was collected within 12 weeks prior to, or those whose 200 mL or more of whole blood was collected within 4 week prior to study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter (Bioequivalence): Maximal Drug Concentration (Cmax) | immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose | Pharmacokinetic parameter: maximal drug concentration (Cmax) was measured in order to confirm bioequivalence. Cmax was measured in nanograms per milliliter (ng/mL). Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose). |
| Pharmacokinetic Parameter (Bioequivalence): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24]) | immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose | Pharmacokinetic parameter: Area under the plasma concentration- time curve from time 0 (administration of the drug) to time 24 hours was measured in order to confirm bioequivalence. AUC was measured in nanogram hours per milliliter (ng\*h/mL). Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose). |
| Pharmacokinetic Parameter (Food Effect): Maximal Drug Concentration (Cmax) | immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose | Pharmacokinetic parameter: maximal drug concentration (Cmax) was measured in order to investigate the effect of food. Cmax was measured in nanograms per milliliter (ng/mL) and was measured under fasted and fed conditions. Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose). |
| Pharmacokinetic Parameter (Food Effect): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24]) | immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose | Pharmacokinetic parameter: Area under the plasma concentration- time curve from time 0 (administration of the drug) to time 24 hours was measured in order to investigate the effect of food. AUC was measured in nanogram hours per milliliter (ng\*h/mL) and was measured under fasted and fed conditions. Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: Eszopiclone One 3 mg Tab First, Then Three 1mg Tabs Participants received Eszopiclone one 3 mg tablets administered orally with water in the morning after fasting for 10 or more hours for 3 days in Period I. After a washout period of 5 or more days, participants were crossed over and received Eszopiclone three 1 mg tablets with water in the morning after fasting for 10 or more hours for 3 days in Period II. At least a 5 day period passed before post treatment examinations. | 20 |
| Group B: Eszopiclone Three 1 mg Tabs First, Then One 3 mg Tab Participants received Eszopiclone three 1 mg tablets administered orally with water in the morning after fasting for 10 or more hours for 3 days in Period I. After a washout period of 5 or more days, participants were crossed over and received Eszopiclone one 3 mg tablets with water in the morning after fasting for 10 or more hours for 3 days in Period II.
After Period II there was at least a 5 day washout period. Certain participants from Group B only proceeded to Period III where they received Eszopiclone one 3 mg tablet taken orally with water, 30 minutes after the start of breakfast for 3 days. At least a 5 day period passed before post treatment examinations. | 21 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period I | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Group A: Eszopiclone One 3 mg Tab First, Then Three 1mg Tabs | Group B: Eszopiclone Three 1 mg Tabs First, Then One 3 mg Tab | Total |
|---|---|---|---|
| Age Continuous | 29.3 years STANDARD_DEVIATION 6 | 33.0 years STANDARD_DEVIATION 9.4 | 31.2 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 42 | 4 / 41 | 0 / 14 | 1 / 14 |
| serious Total, serious adverse events | 0 / 42 | 0 / 41 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Pharmacokinetic Parameter (Bioequivalence): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24])
Pharmacokinetic parameter: Area under the plasma concentration- time curve from time 0 (administration of the drug) to time 24 hours was measured in order to confirm bioequivalence. AUC was measured in nanogram hours per milliliter (ng\*h/mL). Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose).
Time frame: immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose
Population: Pharmacokinetic analysis set (bioequivalence set): All participants who completed the study and had their samples analyzed, except for one participant in Group A who discontinued the study in Period 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone One 3 mg Tablet | Pharmacokinetic Parameter (Bioequivalence): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24]) | 212.59 ng*h/mL | Standard Deviation 34.18 |
| Eszopiclone Three 1 mg Tablets | Pharmacokinetic Parameter (Bioequivalence): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24]) | 210.03 ng*h/mL | Standard Deviation 31.77 |
Primary
Pharmacokinetic Parameter (Bioequivalence): Maximal Drug Concentration (Cmax)
Pharmacokinetic parameter: maximal drug concentration (Cmax) was measured in order to confirm bioequivalence. Cmax was measured in nanograms per milliliter (ng/mL). Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose).
Time frame: immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose
Population: Pharmacokinetic analysis set (bioequivalence set): All participants who completed the study and had their samples analyzed, except for one participant in Group A who discontinued the study in Period 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone One 3 mg Tablet | Pharmacokinetic Parameter (Bioequivalence): Maximal Drug Concentration (Cmax) | 40.80 ng/mL | Standard Deviation 12.39 |
| Eszopiclone Three 1 mg Tablets | Pharmacokinetic Parameter (Bioequivalence): Maximal Drug Concentration (Cmax) | 40.21 ng/mL | Standard Deviation 11.72 |
Primary
Pharmacokinetic Parameter (Food Effect): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24])
Pharmacokinetic parameter: Area under the plasma concentration- time curve from time 0 (administration of the drug) to time 24 hours was measured in order to investigate the effect of food. AUC was measured in nanogram hours per milliliter (ng\*h/mL) and was measured under fasted and fed conditions. Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose).
Time frame: immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose
Population: Pharmacokinetic analysis set (food effect): 14 participants who completed both Period II and Period III, who had been assigned to move on to Period III when assigned to treatment groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone One 3 mg Tablet | Pharmacokinetic Parameter (Food Effect): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24]) | Fasted AUC [0-24] | 199.17 ng*hr/mL | Standard Deviation 38 |
| Eszopiclone One 3 mg Tablet | Pharmacokinetic Parameter (Food Effect): Area Under the Plasma Concentration- Time Curve From Time 0 to Time 24 Hours (AUC[0-24]) | Fed AUC [0-24] | 194.53 ng*hr/mL | Standard Deviation 29.58 |
Primary
Pharmacokinetic Parameter (Food Effect): Maximal Drug Concentration (Cmax)
Pharmacokinetic parameter: maximal drug concentration (Cmax) was measured in order to investigate the effect of food. Cmax was measured in nanograms per milliliter (ng/mL) and was measured under fasted and fed conditions. Blood sampling was calculated immediately before administration of the study drug and 24 hours after administration of the study drug (0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose).
Time frame: immediately before administration & 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 hours post-dose
Population: Pharmacokinetic analysis set (food effect): 14 participants who completed both Period II and Period III, who had been assigned to move on to Period III when assigned to treatment groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszopiclone One 3 mg Tablet | Pharmacokinetic Parameter (Food Effect): Maximal Drug Concentration (Cmax) | Fasted Cmax | 37.59 ng/mL | Standard Deviation 8.7 |
| Eszopiclone One 3 mg Tablet | Pharmacokinetic Parameter (Food Effect): Maximal Drug Concentration (Cmax) | Fed Cmax | 26.56 ng/mL | Standard Deviation 6.75 |