Non-24-Hour-Sleep-Wake Disorder
Conditions
Keywords
Non-24, absolute bioavailability, tasimelteon, Hetlioz™
Brief summary
Hetlioz™ (tasimelteon) is used in the treatment of Non-24-Hour-Sleep-Wake Disorder (Non-24). Non-24 is very common in people who are totally blind because light can not reset their body clock. This causes the internal sleep-wake cycle to be out of sync with the 24-hour day-night. Non-24 is a serious, chronic circadian rhythm disorder in the blind that causes nighttime sleep problems and a wide range of daytime difficulties, including an overwhelming urge to nap. Tasimelteon will be given in two ways; orally (by mouth) as a 20 mg capsule and intravenously (I.V.) by infusion through a catheter (not an injection) into a vein. The oral administration is approved by the FDA. The I.V. administration is considered investigational as it has not been approved by the FDA. This will be the first time tasimelteon will be given to humans by intravenous (I.V.) injection. The purposes of this research study are to: * assess how quickly a single 20 mg oral dose of tasimelteon is absorbed into the body; * evaluate the single-dose pharmacokinetics of tasimelteon after a single 20 mg oral dose and after a single 2 mg I.V. dose; * evaluate the single-dose pharmacokinetics of tasimelteon metabolites after a single 20 mg oral dose and after a single 2 mg I.V. dose; * evaluate the safety and tolerability of a single 20 mg oral dose of tasimelteon; and * evaluate the safety and tolerability of a single 2 mg I.V. dose of tasimelteon. Pharmacokinetics (PK) is the study of how a drug is absorbed, distributed, metabolized, and eventually eliminated by the body. Pharmacokinetics is what the body does to the drug. Blood samples will be taken throughout the study for PK analysis.
Interventions
DRUGtasimelteon 20 mg capsule
DRUGtasimelteon 2 mg I.V.
Sponsors
Vanda Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Men and women ages 18 - 55 years, inclusive; 2. Non-smokers \[abstinence from smoking for at least 6 months before the screening visit\] and test negative for cotinine at screening and baseline; 3. Subjects with Body Mass Index (BMI) of ≥18 and ≤25 kg/m2 (BMI = weight (kg)/ \[height (m)\]2); 4. Males, non-fecund females (i.e., surgically sterilized, if procedure was done 6 months before screening or subject is postmenopausal, without menses for 6 months before screening), or females of child-bearing potential using an acceptable method of birth control for a period of 35 days before the first dosing, and females must have a negative pregnancy test at the screening and baseline visits; Note 1: Acceptable methods of birth control include any one of the following: abstinence, vasectomized sexual partner, hormonal methods (i.e. pill, hormonal IUD, Depo-Provera, implants, patch, intravaginal device \[NuvaRing\]), intrauterine device (IUD \[copper banded coils\]), diaphragm, cervical cap, or condom with spermicidal jelly or foam 5. Vital signs (after 3 minutes resting in a semi-supine position) which are within the ranges shown below: 1. Body temperature between 35.0-37.5 °C; 2. Systolic blood pressure between 90-150 mmHg; 3. Diastolic blood pressure between 50-95 mmHg; 4. Pulse rate between 50-100 bpm. 6. Ability and acceptance to provide written informed consent; 7. Willing and able to comply with study requirements and restrictions; 8. Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis;
Exclusion criteria
1. History of recent (within six months) drug or alcohol abuse as defined in DSM-V, Diagnostic Criteria for Drug and Alcohol Abuse or evidence of such abuse as indicated by the laboratory assays conducted during the Screening Visit or at Baseline; 2. Any major surgery within three months of the first Baseline visit or any minor surgery within one month; 3. History or current evidence of cardiovascular, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction or psychiatric disease judged by the Investigator to be clinically significant; 4. Subjects who are currently considered a suicide risk, any subject who has ever made a suicide attempt, or those who are currently demonstrating active (within the past 6 months) suicidal ideation as deemed by the Columbia Suicide Severity Rating Scale (C-SSRS); 5. Any condition requiring the regular use of medication except those listed in Section 8.2; 6. Exposure to any investigational drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of baseline 7. Exposure (within 2 weeks of Day -1) to any over-the-counter medications including melatonin, dietary supplements and/or herbal remedies, except those listed on Section 8.2; 8. Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit; 9. History of intolerance and/or hypersensitivity to tasimelteon, and/or drugs similar to tasimelteon including melatonin; 10. Donation or loss of 400 mL or more of blood within one month prior to the Baseline Visit; 11. Significant illness within the two weeks prior to Baseline; 12. Pregnant or lactating females; 13. History of porphyria or liver disease and/or positive for one or more of the following serological results: 1. A positive hepatitis C antibody test (anti-HCV) 2. A positive hepatitis B surface antigen (HBsAg) 3. A positive HIV test result 14. Use of any food or beverage containing grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g. kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard greens) and charbroiled meats for at least 2 weeks before the Baseline Visit until the end of the study; 15. Inability to be venipunctured and/or tolerate venous access; 16. Previous participation in a BMS-214778, VEC-162, or tasimelteon study; 17. Subjects who are unable to read or speak English; 18. Any other sound medical reason as determined by the clinical Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability After a Single Oral Dose of Hetlioz™(Tasimelteon) 20mg | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | The absolute bioavailability (F) of tasimelteon will be estimated from the dose-corrected AUC(inf) after oral and I.V. administration using an analysis of variance (ANOVA) model with treatment, period, sequence, and subject within sequence as the classification variables, using natural log-transformed data. The geometric mean ratio (GMR), oral-to-I.V., and its associated 90% confidence interval (CI) will be used as the estimate of F and its variability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | Cmax of tasimelteon will be compared when given orally or administered as an I.V. |
| AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | AUC (inf) of Tasimelteon will be compared when given orally or administered as an I.V. |
| T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours pos-dose | T1/2 of tasimelteon will be compared when given orally or administered as an I.V. |
| Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | CL of tasimelteon will be compared when given orally or administered as an I.V. |
| AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | The mean +/- SD for the AUC(inf) of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon |
| Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | Comparison of the metabolite-to-parent AUC(inf) ratios for the oral and IV routes. |
| Number of Participants With Adverse Events | From Baseline to End of Study; Day 5 (± 2 days). | Number of participants with treatment-emergent adverse event per treatment arm and overall. |
| Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose | The mean +/- SD for the Cmax of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts. | Baseline to End of Study Day 5 (± 2 days). | Number of Participants that reported suicidal ideation, suicidal behavior, or suicide attempts per treatment arm and overall. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Number of Baseline Participants 14 subjects total participated in the study | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Overall Number of Baseline Participants |
|---|---|
| Age, Continuous | 31.2 years STANDARD_DEVIATION 10.6 |
| Body Mass Index | 22.8 (kg/m^2) STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 166.6 (cm) STANDARD_DEVIATION 10.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 7 Participants |
| Weight | 63.6 (kg) STANDARD_DEVIATION 8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 14 | 1 / 14 | 3 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Absolute Bioavailability After a Single Oral Dose of Hetlioz™(Tasimelteon) 20mg
The absolute bioavailability (F) of tasimelteon will be estimated from the dose-corrected AUC(inf) after oral and I.V. administration using an analysis of variance (ANOVA) model with treatment, period, sequence, and subject within sequence as the classification variables, using natural log-transformed data. The geometric mean ratio (GMR), oral-to-I.V., and its associated 90% confidence interval (CI) will be used as the estimate of F and its variability.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Absolute Bioavailability | Absolute Bioavailability After a Single Oral Dose of Hetlioz™(Tasimelteon) 20mg | 38.3 Geometric Mean Ratio (%) |
Secondary
AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
AUC (inf) of Tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Absolute Bioavailability | AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 358 (h*ng/mL) | Standard Deviation 271 |
| IV (2 mg) | AUC (Inf) of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 71.6 (h*ng/mL) | Standard Deviation 23.9 |
Secondary
AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose
The mean +/- SD for the AUC(inf) of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
Population: Only 11 subjects could be analyzed for M11.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Absolute Bioavailability | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M9 | 400 h*ng/mL | Standard Deviation 139 |
| Absolute Bioavailability | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M11 | 125 h*ng/mL | Standard Deviation 43.7 |
| Absolute Bioavailability | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M12 | 619 h*ng/mL | Standard Deviation 364 |
| Absolute Bioavailability | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M13 | 431 h*ng/mL | Standard Deviation 152 |
| IV (2 mg) | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M13 | 38.2 h*ng/mL | Standard Deviation 13 |
| IV (2 mg) | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M9 | 30.3 h*ng/mL | Standard Deviation 10.3 |
| IV (2 mg) | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M12 | 43.8 h*ng/mL | Standard Deviation 25.4 |
| IV (2 mg) | AUC(Inf) of Tasimelteon's Metabolites After a Single Oral and I.V. Dose | M11 | 12.2 h*ng/mL | Standard Deviation 4.4 |
Secondary
Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
Cmax of tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Absolute Bioavailability | Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 260 ng/mL | Standard Deviation 189 |
| IV (2 mg) | Cmax of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 82.2 ng/mL | Standard Deviation 20.5 |
Secondary
Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon
The mean +/- SD for the Cmax of tasimelteon's metabolites after a single 20 mg oral dose of tasimelteon and after a single 2 mg I.V. administration of tasimelteon
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Absolute Bioavailability | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M9 | 303 ng/mL | Standard Deviation 94.3 |
| Absolute Bioavailability | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M11 | 53.2 ng/mL | Standard Deviation 16.14 |
| Absolute Bioavailability | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M12 | 113 ng/mL | Standard Deviation 30.8 |
| Absolute Bioavailability | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M13 | 370 ng/mL | Standard Deviation 105 |
| IV (2 mg) | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M13 | 29 ng/mL | Standard Deviation 11.7 |
| IV (2 mg) | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M9 | 16.4 ng/mL | Standard Deviation 6.16 |
| IV (2 mg) | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M12 | 7.31 ng/mL | Standard Deviation 2.49 |
| IV (2 mg) | Cmax of Tasimelteon's Metabolites After an Oral and I.V. Dose of Tasimelteon | M11 | 3.7 ng/mL | Standard Deviation 1.25 |
Secondary
Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon
Comparison of the metabolite-to-parent AUC(inf) ratios for the oral and IV routes.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Absolute Bioavailability | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M9 | 1.98 metabolite to parent AUC (inf) ratios | Standard Deviation 2.65 |
| Absolute Bioavailability | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M11 | 0.51 metabolite to parent AUC (inf) ratios | Standard Deviation 0.35 |
| Absolute Bioavailability | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M12 | 2.04 metabolite to parent AUC (inf) ratios | Standard Deviation 0.93 |
| Absolute Bioavailability | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M13 | 1.72 metabolite to parent AUC (inf) ratios | Standard Deviation 1.12 |
| IV (2 mg) | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M13 | 0.51 metabolite to parent AUC (inf) ratios | Standard Deviation 0.14 |
| IV (2 mg) | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M9 | 0.39 metabolite to parent AUC (inf) ratios | Standard Deviation 0.12 |
| IV (2 mg) | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M12 | 0.54 metabolite to parent AUC (inf) ratios | Standard Deviation 0.15 |
| IV (2 mg) | Metabolite-to-parent AUC(Inf) Ratios After Oral Administration of a Single 20 mg Dose and IV Administration of a Single 2 mg Dose of Tasimelteon | M11 | 0.16 metabolite to parent AUC (inf) ratios | Standard Deviation 0.03 |
Secondary
Number of Participants With Adverse Events
Number of participants with treatment-emergent adverse event per treatment arm and overall.
Time frame: From Baseline to End of Study; Day 5 (± 2 days).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Absolute Bioavailability | Number of Participants With Adverse Events | headache | 1 participants |
| Absolute Bioavailability | Number of Participants With Adverse Events | vomiting | 0 participants |
| Absolute Bioavailability | Number of Participants With Adverse Events | Somnolance | 1 participants |
| IV (2 mg) | Number of Participants With Adverse Events | headache | 1 participants |
| IV (2 mg) | Number of Participants With Adverse Events | vomiting | 1 participants |
| IV (2 mg) | Number of Participants With Adverse Events | Somnolance | 0 participants |
| All Subjects | Number of Participants With Adverse Events | vomiting | 1 participants |
| All Subjects | Number of Participants With Adverse Events | Somnolance | 1 participants |
| All Subjects | Number of Participants With Adverse Events | headache | 2 participants |
Secondary
T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
T1/2 of tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours pos-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Absolute Bioavailability | T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 1.06 hour | Standard Deviation 0.23 |
| IV (2 mg) | T1/2 of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 1.02 hour | Standard Deviation 0.23 |
Secondary
Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration.
CL of tasimelteon will be compared when given orally or administered as an I.V.
Time frame: pre-dose, -0.125, 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Absolute Bioavailability | Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 2241 (mL/min) | Standard Deviation 3592 |
| IV (2 mg) | Total Clearance of Tasimelteon After a Single 20 mg Oral Dose and After a Single 2 mg I.V. Administration. | 505 (mL/min) | Standard Deviation 135 |
Other Pre-specified
Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts.
Number of Participants that reported suicidal ideation, suicidal behavior, or suicide attempts per treatment arm and overall.
Time frame: Baseline to End of Study Day 5 (± 2 days).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Absolute Bioavailability | Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts. | 0 participants |
| IV (2 mg) | Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts. | 0 participants |
| All Subjects | Number of Participants That Reported Suicidal Ideation, Suicidal Behavior, or Suicide Attempts. | 0 participants |