COVID-19
Conditions
Keywords
Coronavirus, Covid-19, Double Blind, Healthy Volunteers, Multiple Ascending Dose, Phase 1, Placebo Controlled, Randomized, SLV213
Brief summary
This Phase 1 double blind, placebo-controlled study will evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses (MAD) of SLV213 in healthy male and female participants, 18-65 years of age. This study will help to select the most likely suitable dose (e.g., at Maximum Tolerated Dose \[MTD\]) for the treatment of patients with COVID-19 in a pivotal study. This phase 1 double blind, placebo-controlled study will consist of three sequential cohorts of 12 participants each (8 SLV213 and 4 placebo), at doses of 400 mg every 12 hours (Q12h), 600 mg Q12h, and 800 mg Q12h administered orally (PO) for 7 days. After each cohort, a Safety Review Committee (SRC) will evaluate the safety of the regimen before proceeding to dose the next cohort. Randomization will occur into the respective cohorts as above. Upon meeting the Inclusion/Exclusion criteria, subjects will begin treatment with SLV213 or placebo per their assigned cohort. The primary objective is to evaluate the safety and tolerability of multiple ascending doses of SLV213 for 7 days in healthy participants.
Detailed description
This Phase 1 double blind, placebo-controlled study will evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses (MAD) of SLV213 in healthy male and female participants, 18-65 years of age. This study will help to select the most likely suitable dose (e.g., at Maximum Tolerated Dose \[MTD\]) for the treatment of patients with COVID-19 in a pivotal study. This phase 1 double blind, placebo-controlled study will consist of three sequential cohorts of 12 participants each (8 SLV213 and 4 placebo), at doses of 400 mg every 12 hours (Q12h), 600 mg Q12h, and 800 mg Q12h administered orally (PO) for 7 days. After each cohort, a Safety Review Committee (SRC) will evaluate the safety of the regimen before proceeding to dose the next cohort. Randomization will occur into the respective cohorts as above. Upon meeting the Inclusion/Exclusion criteria, subjects will begin treatment with SLV213 or placebo per their assigned cohort. Participants will take their study drug in the fasted state prior to morning and evening meals and will remain as in-patient in the clinical trial unit (CTU) during all treatments and for approximately 48 hours (h) after the last dose for monitoring. After discharge from the CTU, participants will be monitored by CTU staff by telephone to assess for new adverse events and use of concomitant medication since the last visit or contact, approximately weekly for three weeks. Participants will be asked to return to the CTU for further assessment of moderate or severe adverse events (AEs) use of concomitant medications (ConMeds) since the last visit or contact, approximately weekly for three weeks. The primary objective is to evaluate the safety and tolerability of multiple ascending doses of SLV213 for 7 days in healthy participants. The secondary objective is to characterize the multiple dose PK of SLV213 in healthy participants.
Interventions
OTHERPlacebo for SLV213
Microcrystalline cellulose in a size 1 orange hard gelatin capsule.
DRUGSLV213
SLV213 drug substance (K777) is 4-methylpiperazine-1-carboxylic acid, a vinyl sulfone cysteine protease inhibitor for the treatment of subjects infected with SARS-CoV-2. SLV213 is a white powder substance without excipients or stabilizer that will be packed into gelatin capsules which has been demonstrated to exhibit broad inhibitory properties against host cathepsins (e.g., Cathepsin L).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form. 2. Able to understand and willing to be available for all study visits and comply with all study procedures including Lifestyle Considerations throughout the study. 3. Male and Female individuals, age 18-65 inclusive at time of enrollment. 4. Good general health by medical history (MH), physical examination (PE), and vital signs (VS), clinical laboratory tests and Electrocardiogram (ECG) within normal reference range. Note 1: Lab exceptions include: lab test values that are within Grade 1 range per the Toxicity Table (Appendix A) are acceptable if not considered to be clinically significant by the investigator (PI, sub-investigator, or authorized clinician), with the exception of liver function tests (LFT) (transaminases Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), alkaline phosphatase (AP), total and direct bilirubin, serum creatinine, estimated glomerular filtration rate (eGFR) per the CKD-EPI formula, and urine protein, which must be within the laboratory normal reference range. Note 2: Screening laboratory values that fall outside the laboratory normal reference ranges and the ranges are not listed within the Toxicity Table (Appendix A) (e.g., decrease activated partial thromboplastin time (aPTT)) that are deemed Not Clinically Significant by the PI will be acceptable. 5. Ability to take oral medication and be willing to adhere to the dosing regimen. 6. Women of childbearing potential1 must have practiced or use true abstinence2 or use at least one acceptable primary form of contraception3 for specified periods4 before, during and after dosing. Note 1: Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, salpingectomy, tubal ligation, or Essure placement with a history of documented radiological confirmation test at least 90 days after the procedure). Note 2: True abstinence is 100% of the time without sexual intercourse (the male's penis enters the female's vagina). Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception). Note 3: Acceptable forms of primary contraception include a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more before the participant receiving the study product, tubal ligation, non-hormonal, intrauterine device, (and if in a monogamous relationship with a male partner who uses a barrier method without spermicide) Note 4: Specified periods include at least 30 days prior to screening, during the period between screening and completion of dosing, and until at least 30 days following receipt of the last dose of study product. 7. Women of childbearing potential must have a negative serum Beta-human chorionic gonadotropin (HCG) pregnancy test at screening and a negative urine HCG pregnancy test at check-in (Day-1) within 24 hours before receiving the initial study product. 8. Male participants receiving the study product must use acceptable contraception and refrain from donating sperm from the day of first dose until 30 days after the last dose or be vasectomized.1 Note 1: Acceptable contraception includes abstinence from intercourse with a female of childbearing potential or use of a male condom without spermicide when engaging in any activity that allows for the passage of ejaculate to a female during the intervention period and for at least 30 days after ending study dosing, or surgical sterilization for 180 days or more. 9. Willing to avoid excessive physical exercise starting within 48 h prior to dosing and until discharge from the CTU on Day 9. 10. No history of acute febrile or infectious illness for at least 7 days prior to the administration of study drug.
Exclusion criteria
1. Pregnant or lactating. 2. History of any chronic disease that may increase risk to subject or interfere with endpoint assessment1: Note 1: With the exception of stable chronic medical conditions that do not require prescribed oral or injectable medications (e.g., Type 2 diabetes managed by diet only). 3. History of bradycardia, orthostatic hypotension or orthostatic tachycardia, Long COVID or history of dysautonomia.1 Note 1: Exception is sinus bradycardia (HR \<60 bpm) in healthy participants (e.g., conditioned athletes) could be enrolled per investigator's clinical judgement. 4. Known history of a clinically significant food or drug allergy/hypersensitivity including known allergy/hypersensitivity to ingredients of the study drug or placebo. 5. Current seasonal allergies with ongoing symptoms for more than a week prior to dosing requiring glucocorticoids and/or frequent use of antihistamines for treatment. 6. History of any clinically significant disease or disorder, medical/surgical procedure, or trauma within 4 weeks prior to initiation of administration of study product(s). 7. History of any psychiatric condition that has required hospitalization in the last 12 months or subject is considered psychologically unstable by the investigator. 8. History of any substance use disorder or positive urine drug screening (UDS) test for illicit substances at Screening or Check-in (Day -1)1. Note 1: Any approved medical use of amphetamines, barbiturates, benzodiazepines, cannabis, tricyclic antidepressants and opiates will not be acceptable. 9. History of alcoholism or of binge1 or heavy alcohol drinking2 at any time in the 6 months before study product administration or positive urine alcohol test at Screening or Check-in (Day -1). Note 1: Binge drinking is defined as 5 or more drinks during a single occasion if male, or 4 or more if female. Note 2: Heavy drinking of alcohol is defined as consumption of more than 14 drinks of alcohol per week if male, or more than 7 drinks if female. 10. History of \>/=10 pack-years of nicotine product1 consumption in the 5-year period before screening, or positive urine cotinine screen at Check-in (Day -1)2. Note 1: Nicotine products include cigarettes, e-cigarettes, pipe, cigar, chewing tobacco, nicotine patch. Note 2: Positive urine cotinine at Screening is allowed if negative at Check-in (Day -1). 11. Body mass index (BMI) \</= 18 kg/m2 or \>/= 32 kg/m2, or weight \</= 100 lbs at Screening. 12. Prior exposure to SLV213 or K777 or K11777. 13. Use of any prohibited prescription or non-prescription medication within 14 days or 5 half-lives of the drug, whichever is longer, prior to study Check-in. 14. Use of any investigational drug product within 30 days or 5 half-lives (whichever is longer) before investigational product administration in this study. 15. Planned participation in a clinical research study that requires treatment with a study drug, blood draws or other invasive assessments during the study period (screening until final visit). 16. Blood or plasma donation of 500 mL within 3 months or more than 100 mL within 30 days before signing informed consent or planned donation prior to completion of this trial. 17. Positive viral serology tests for Human Immunodeficiency Virus (HIV), hepatitis B virus, or hepatitis C virus (HCV) at screening1 with one exception2: Note 1: Viral serology tests include HIV 1 and HIV 2 antibodies, Hepatitis B virus surface antigen (HBsAg), and HCV antibodies. Note 2: Do not exclude participants with HCV antibodies who have been successfully treated for Hepatitis C, do not take any treatment medications currently, do not use prohibited medications, have normal transaminases and are generally healthy. 18. Positive SARS-CoV-2 (COVID-19) molecular diagnostic test (Cue Care™ test) at Check-in (Day -1).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Day 1 through Day 28 | The number of participants who experienced at least one unsolicited TEAE of any relatedness are summarized by the maximum severity recorded. A TEAE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as a TEAE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as a TEAE. |
| Frequency of Related Treatment-Related TEAEs | Day 1 through Day 28 | The number of participants who experienced at least one related unsolicited TEAE of any severity. A TEAE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as a TEAE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as a TEAE. A TEAE is considered related if there is a reasonable possibility that the study intervention caused the TEAE, or there is a temporal relationship between the study intervention and event. |
| Frequency of Serious Adverse Events (SAEs) | Day 1 through Day 28 | The number of participants who experienced at least one SAE throughout the course of the study. An AE is considered serious if, in the view of either the investigator or sponsor, it results in any of the following outcomes: * Death * A life-threatening adverse event * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or * A congenital anomaly/birth defect. |
| Frequency of Laboratory AEs by Maximum Severity | Day 1 through Day 28 | The number of participants who experienced at least one laboratory AE of any relatedness are summarized by the maximum severity recorded. Graded chemistry measurements include sodium, potassium, carbon dioxide, calcium, creatinine, blood urea nitrogen, fasting glucose, total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, amylase, lipase, magnesium, and inorganic phosphorous. Graded hematology measurements include hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Graded coagulation measurements include prothrombin time and activated partial thromboplastin time. Graded urinalysis measurements include nitrite, urine protein, urine glucose, white blood cells, red blood cells, and bacteria. If a laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity. |
| Frequency of Treatment-Related Laboratory AEs | Day 1 through Day 28 | The number of participants who experienced at least one related laboratory AE of any severity. Graded chemistry measurements include sodium, potassium, carbon dioxide, calcium, creatinine, blood urea nitrogen, fasting glucose, total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, amylase, lipase, magnesium, and inorganic phosphorous. Graded hematology measurements include hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Graded coagulation measurements include prothrombin time and activated partial thromboplastin time. Graded urinalysis measurements include nitrite, urine protein, urine glucose, white blood cells, red blood cells, and bacteria. If a laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity. |
| Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Day 1 through Day 28 | The number of participants who experienced at least one ECG AE of any relatedness are summarized by the maximum severity recorded. Graded ECG parameters include PR Internal and QTcF Interval. |
| Frequency of Treatment-Related ECG AEs | Day 1 through Day 28 | The number of participants who experienced at least one related ECG AE of any severity. Graded ECG parameters include PR Internal and QTcF Interval. |
| Frequency of Early Terminations or Withdrawals Due to Treatment-Related TEAEs | Day 1 through Day 28 | The number of participants who terminated early or were withdrawn due to a treatment-related TEAE. This outcome is used to assess the tolerability of the study treatment. |
| Frequency of TEAEs | Day 1 through Day 28 | The number of participants who experienced at least one TEAE of any severity. This outcome is used to assess the tolerability of the study treatment. |
| Frequency of Grade 3 or Higher Laboratory AEs | Day 1 through Day 28 | The number of participants who experienced at least one Grade 3 (severe) or higher laboratory AE. This outcome is used to assess the tolerability of the study treatment. |
| Frequency of Grade 3 or Higher Vital Signs AEs | Day 1 through Day 28 | The number of participants who experienced at least one Grade 3 (severe) or higher vital signs AE. This outcome is used to assess the tolerability of the study treatment. |
| Frequency of Grade 3 or Higher ECG AEs | Day 1 through Day 28 | The number of participants who experienced at least one Grade 3 (severe) or higher ECG AE. This outcome is used to assess the tolerability of the study treatment. |
| Frequency of Participants Who Received All Oral Medication Doses | Day 1 through Day 28 | The number of participants who received all doses of study product. This outcome is used to assess the tolerability of the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose-normalized Cmax (Cmax/Dose) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Cmax at Steady State (Cmax,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Cmin at Steady State (Cmin,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Average Concentration During the Dosing Interval (Cavg) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Tmax at Steady State (Tmax,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Tmin at Steady State (Tmin,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to 48 h at Steady State (AUC0-48,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| AUC0-tau at Steady State (AUC0-tau,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| t1/2 of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. t1/2 was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax. |
| CLT at Steady State (CLT,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Vd at Steady State (Vd,ss) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Dose-Normalized AUC0-tau,ss (AUC0-tau,ss/Dose) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Dose-Normalized Cmax,ss (Cmax,ss/Dose) of SLV213 in Plasma After Dose 14 | 0 h through 48 h post dose 14 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. |
| Maximum Concentration (Cmax) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Accumulation Ratio for AUC (RAUC) of SLV213 in Plasma | 0 h through 12 h post dose 1, 0 h through 48 h post dose 14 | RAUC is estimated as AUC0-tau,ss (Dose 14)/AUC0-tau (Dose 1). PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 and dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. |
| Accumulation Ratio for Cmax (RCmax) of SLV213 in Plasma | 0 h through 12 h post dose 1, 0 h through 48 h post dose 14 | RCmax is estimated as Cmax,ss (Dose 14)/Cmax (Dose 1). PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 and dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. |
| Linearity Index of SLV213 in Plasma | 0 h through 12 h post dose 1, 0 h through 48 h post dose 14 | Linearity index is estimated as AUC0-tau,ss (Dose 14)/AUC0-inf (Dose 1). PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 and dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. |
| Minimum Concentration (Cmin) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Time of Maximum Concentration (Tmax) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Time of Minimum Concentration (Tmin) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to Infinity (AUC0-inf) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. AUC0-inf was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax. |
| Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to 12 h (AUC0-12) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the Last Concentration Above the Lower Limit of Quantitation (AUC0-last) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the End of the Dosing Interval (AUC0-tau) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
| Terminal Half-Life (t1/2) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. t1/2 was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax. |
| Total Clearance (CLT) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. CLT was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax. |
| Terminal Phase Elimination Rate Constant (Ke) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. Ke was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax. |
| Volume of Distribution (Vd) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. Vd was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax. |
| Dose-normalized AUC0-Tau (AUC0-tau/Dose) of SLV213 in Plasma After Dose 1 | 0 h through 12 h post dose 1 | PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. |
Countries
United States
Participant flow
Recruitment details
The study population included healthy male and female adults, ages 18-65, inclusive, who met all eligibility criteria. Participants were enrolled at a single clinical trial unit between April 9, 2024 and June 10, 2024 and were recruited via IRB-approved strategies, including direct mailing, recruitment from an IRB-approved trial registry and local advertisements/flyers.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - 400 mg SLV213 400 mg (4 x 100 mg capsules) of SLV213 administered orally every 12 hours for 7 days to healthy male and female participants 18-65 years of age. | 11 |
| Placebo Placebo participants from Cohort 1. Placebo capsules were administered by the same route as active drug. | 5 |
| Total | 16 |
Baseline characteristics
| Characteristic | Cohort 1 - 400 mg SLV213 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 11.7 | 40.2 years STANDARD_DEVIATION 14.1 | 45.1 years STANDARD_DEVIATION 12.5 |
| Body Mass Index (BMI) | 27.51 kg/m^2 STANDARD_DEVIATION 3.33 | 27.70 kg/m^2 STANDARD_DEVIATION 4.41 | 27.57 kg/m^2 STANDARD_DEVIATION 3.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 4 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 5 |
| other Total, other adverse events | 11 / 11 | 5 / 5 |
| serious Total, serious adverse events | 0 / 11 | 0 / 5 |
Outcome results
Primary
Frequency of Early Terminations or Withdrawals Due to Treatment-Related TEAEs
The number of participants who terminated early or were withdrawn due to a treatment-related TEAE. This outcome is used to assess the tolerability of the study treatment.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Early Terminations or Withdrawals Due to Treatment-Related TEAEs | 1 Participants |
| Placebo | Frequency of Early Terminations or Withdrawals Due to Treatment-Related TEAEs | 0 Participants |
Primary
Frequency of Electrocardiogram (ECG) AEs by Maximum Severity
The number of participants who experienced at least one ECG AE of any relatedness are summarized by the maximum severity recorded. Graded ECG parameters include PR Internal and QTcF Interval.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | None | 11 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Mild | 0 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Moderate | 0 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Severe | 0 Participants |
| Placebo | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Severe | 0 Participants |
| Placebo | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | None | 4 Participants |
| Placebo | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Moderate | 0 Participants |
| Placebo | Frequency of Electrocardiogram (ECG) AEs by Maximum Severity | Mild | 1 Participants |
Primary
Frequency of Grade 3 or Higher ECG AEs
The number of participants who experienced at least one Grade 3 (severe) or higher ECG AE. This outcome is used to assess the tolerability of the study treatment.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Grade 3 or Higher ECG AEs | 0 Participants |
| Placebo | Frequency of Grade 3 or Higher ECG AEs | 0 Participants |
Primary
Frequency of Grade 3 or Higher Laboratory AEs
The number of participants who experienced at least one Grade 3 (severe) or higher laboratory AE. This outcome is used to assess the tolerability of the study treatment.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Grade 3 or Higher Laboratory AEs | 1 Participants |
| Placebo | Frequency of Grade 3 or Higher Laboratory AEs | 0 Participants |
Primary
Frequency of Grade 3 or Higher Vital Signs AEs
The number of participants who experienced at least one Grade 3 (severe) or higher vital signs AE. This outcome is used to assess the tolerability of the study treatment.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Grade 3 or Higher Vital Signs AEs | 0 Participants |
| Placebo | Frequency of Grade 3 or Higher Vital Signs AEs | 0 Participants |
Primary
Frequency of Laboratory AEs by Maximum Severity
The number of participants who experienced at least one laboratory AE of any relatedness are summarized by the maximum severity recorded. Graded chemistry measurements include sodium, potassium, carbon dioxide, calcium, creatinine, blood urea nitrogen, fasting glucose, total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, amylase, lipase, magnesium, and inorganic phosphorous. Graded hematology measurements include hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Graded coagulation measurements include prothrombin time and activated partial thromboplastin time. Graded urinalysis measurements include nitrite, urine protein, urine glucose, white blood cells, red blood cells, and bacteria. If a laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Laboratory AEs by Maximum Severity | None | 0 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Laboratory AEs by Maximum Severity | Mild | 10 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Laboratory AEs by Maximum Severity | Moderate | 0 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Laboratory AEs by Maximum Severity | Severe | 1 Participants |
| Placebo | Frequency of Laboratory AEs by Maximum Severity | Severe | 0 Participants |
| Placebo | Frequency of Laboratory AEs by Maximum Severity | None | 0 Participants |
| Placebo | Frequency of Laboratory AEs by Maximum Severity | Moderate | 1 Participants |
| Placebo | Frequency of Laboratory AEs by Maximum Severity | Mild | 4 Participants |
Primary
Frequency of Participants Who Received All Oral Medication Doses
The number of participants who received all doses of study product. This outcome is used to assess the tolerability of the study treatment.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Participants Who Received All Oral Medication Doses | 8 Participants |
| Placebo | Frequency of Participants Who Received All Oral Medication Doses | 4 Participants |
Primary
Frequency of Related Treatment-Related TEAEs
The number of participants who experienced at least one related unsolicited TEAE of any severity. A TEAE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as a TEAE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as a TEAE. A TEAE is considered related if there is a reasonable possibility that the study intervention caused the TEAE, or there is a temporal relationship between the study intervention and event.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Related Treatment-Related TEAEs | 11 Participants |
| Placebo | Frequency of Related Treatment-Related TEAEs | 5 Participants |
Primary
Frequency of Serious Adverse Events (SAEs)
The number of participants who experienced at least one SAE throughout the course of the study. An AE is considered serious if, in the view of either the investigator or sponsor, it results in any of the following outcomes: * Death * A life-threatening adverse event * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or * A congenital anomaly/birth defect.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Serious Adverse Events (SAEs) | 0 Participants |
| Placebo | Frequency of Serious Adverse Events (SAEs) | 0 Participants |
Primary
Frequency of TEAEs
The number of participants who experienced at least one TEAE of any severity. This outcome is used to assess the tolerability of the study treatment.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of TEAEs | 11 Participants |
| Placebo | Frequency of TEAEs | 5 Participants |
Primary
Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity
The number of participants who experienced at least one unsolicited TEAE of any relatedness are summarized by the maximum severity recorded. A TEAE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. A TEAE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as a TEAE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as a TEAE.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | None | 0 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Mild | 7 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Moderate | 4 Participants |
| Cohort 1 - 400 mg SLV213 | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Severe | 0 Participants |
| Placebo | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Severe | 0 Participants |
| Placebo | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | None | 0 Participants |
| Placebo | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Moderate | 2 Participants |
| Placebo | Frequency of Treatment-Emergent Adverse Events (TEAEs) by Maximum Severity | Mild | 3 Participants |
Primary
Frequency of Treatment-Related ECG AEs
The number of participants who experienced at least one related ECG AE of any severity. Graded ECG parameters include PR Internal and QTcF Interval.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Treatment-Related ECG AEs | 0 Participants |
| Placebo | Frequency of Treatment-Related ECG AEs | 1 Participants |
Primary
Frequency of Treatment-Related Laboratory AEs
The number of participants who experienced at least one related laboratory AE of any severity. Graded chemistry measurements include sodium, potassium, carbon dioxide, calcium, creatinine, blood urea nitrogen, fasting glucose, total protein, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, amylase, lipase, magnesium, and inorganic phosphorous. Graded hematology measurements include hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, basophils, and eosinophils. Graded coagulation measurements include prothrombin time and activated partial thromboplastin time. Graded urinalysis measurements include nitrite, urine protein, urine glucose, white blood cells, red blood cells, and bacteria. If a laboratory value met the threshold for an AE at baseline, subsequent safety laboratory results were only considered to be an AE if the grading worsened in severity.
Time frame: Day 1 through Day 28
Population: The safety population includes all participants who received at least one dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Frequency of Treatment-Related Laboratory AEs | 11 Participants |
| Placebo | Frequency of Treatment-Related Laboratory AEs | 5 Participants |
Secondary
Accumulation Ratio for AUC (RAUC) of SLV213 in Plasma
RAUC is estimated as AUC0-tau,ss (Dose 14)/AUC0-tau (Dose 1). PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 and dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1, 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Accumulation Ratio for AUC (RAUC) of SLV213 in Plasma | 0.641 ratio | Geometric Coefficient of Variation 40 |
Secondary
Accumulation Ratio for Cmax (RCmax) of SLV213 in Plasma
RCmax is estimated as Cmax,ss (Dose 14)/Cmax (Dose 1). PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 and dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1, 0 h through 48 h post dose 14
Population: 0 h through 12 h post dose 1, 0 h through 48 h post dose 14
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Accumulation Ratio for Cmax (RCmax) of SLV213 in Plasma | 0.598 ratio | Geometric Coefficient of Variation 47 |
Secondary
Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to 12 h (AUC0-12) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to 12 h (AUC0-12) of SLV213 in Plasma After Dose 1 | 2172.4 ng*h/mL | Geometric Coefficient of Variation 64 |
Secondary
Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to 48 h at Steady State (AUC0-48,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to 48 h at Steady State (AUC0-48,ss) of SLV213 in Plasma After Dose 14 | 1734.6 ng*h/mL | Geometric Coefficient of Variation 56 |
Secondary
Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to Infinity (AUC0-inf) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. AUC0-inf was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to Infinity (AUC0-inf) of SLV213 in Plasma After Dose 1 | 2234.6 ng*h/mL | Geometric Coefficient of Variation 65 |
Secondary
Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the End of the Dosing Interval (AUC0-tau) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the End of the Dosing Interval (AUC0-tau) of SLV213 in Plasma After Dose 1 | 2172.4 ng*h/mL | Geometric Coefficient of Variation 64 |
Secondary
Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the Last Concentration Above the Lower Limit of Quantitation (AUC0-last) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the Last Concentration Above the Lower Limit of Quantitation (AUC0-last) of SLV213 in Plasma After Dose 1 | 2157.5 ng*h/mL | Geometric Coefficient of Variation 66 |
Secondary
AUC0-tau at Steady State (AUC0-tau,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | AUC0-tau at Steady State (AUC0-tau,ss) of SLV213 in Plasma After Dose 14 | 1624.4 ng*h/mL | Geometric Coefficient of Variation 58 |
Secondary
Average Concentration During the Dosing Interval (Cavg) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Average Concentration During the Dosing Interval (Cavg) of SLV213 in Plasma After Dose 14 | 135.2 ng/mL | Geometric Coefficient of Variation 58 |
Secondary
CLT at Steady State (CLT,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | CLT at Steady State (CLT,ss) of SLV213 in Plasma After Dose 14 | 246.1 L/h | Geometric Coefficient of Variation 58 |
Secondary
Cmax at Steady State (Cmax,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Cmax at Steady State (Cmax,ss) of SLV213 in Plasma After Dose 14 | 419.0 ng/mL | Geometric Coefficient of Variation 58 |
Secondary
Cmin at Steady State (Cmin,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Cmin at Steady State (Cmin,ss) of SLV213 in Plasma After Dose 14 | 23.66 ng/mL | Geometric Coefficient of Variation 47 |
Secondary
Dose-normalized AUC0-Tau (AUC0-tau/Dose) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Dose-normalized AUC0-Tau (AUC0-tau/Dose) of SLV213 in Plasma After Dose 1 | 5.428 ng*h/mL/mg | Geometric Coefficient of Variation 64 |
Secondary
Dose-Normalized AUC0-tau,ss (AUC0-tau,ss/Dose) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Dose-Normalized AUC0-tau,ss (AUC0-tau,ss/Dose) of SLV213 in Plasma After Dose 14 | 4.061 ng*h/mL/mg | Geometric Coefficient of Variation 58 |
Secondary
Dose-normalized Cmax (Cmax/Dose) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Dose-normalized Cmax (Cmax/Dose) of SLV213 in Plasma After Dose 1 | 1.544 ng/mL/mg | Geometric Coefficient of Variation 65 |
Secondary
Dose-Normalized Cmax,ss (Cmax,ss/Dose) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Dose-Normalized Cmax,ss (Cmax,ss/Dose) of SLV213 in Plasma After Dose 14 | 1.047 ng/mL/mg | Geometric Coefficient of Variation 58 |
Secondary
Linearity Index of SLV213 in Plasma
Linearity index is estimated as AUC0-tau,ss (Dose 14)/AUC0-inf (Dose 1). PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 and dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1, 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Linearity Index of SLV213 in Plasma | 0.625 ratio | Geometric Coefficient of Variation 40 |
Secondary
Maximum Concentration (Cmax) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Maximum Concentration (Cmax) of SLV213 in Plasma After Dose 1 | 617.1 ng/mL | Geometric Coefficient of Variation 65 |
Secondary
Minimum Concentration (Cmin) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Minimum Concentration (Cmin) of SLV213 in Plasma After Dose 1 | 22.45 ng/mL | Geometric Coefficient of Variation 43 |
Secondary
t1/2 of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. t1/2 was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | t1/2 of SLV213 in Plasma After Dose 14 | 3.05 h | Geometric Coefficient of Variation 20 |
Secondary
Terminal Half-Life (t1/2) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. t1/2 was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Terminal Half-Life (t1/2) of SLV213 in Plasma After Dose 1 | 2.15 h | Geometric Coefficient of Variation 22 |
Secondary
Terminal Phase Elimination Rate Constant (Ke) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. Ke was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Terminal Phase Elimination Rate Constant (Ke) of SLV213 in Plasma After Dose 1 | 0.3220 1/h | Geometric Coefficient of Variation 22 |
Secondary
Time of Maximum Concentration (Tmax) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Time of Maximum Concentration (Tmax) of SLV213 in Plasma After Dose 1 | 2.00 h |
Secondary
Time of Minimum Concentration (Tmin) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Time of Minimum Concentration (Tmin) of SLV213 in Plasma After Dose 1 | 11.80 h |
Secondary
Tmax at Steady State (Tmax,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Tmax at Steady State (Tmax,ss) of SLV213 in Plasma After Dose 14 | 2.00 h |
Secondary
Tmin at Steady State (Tmin,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - 400 mg SLV213 | Tmin at Steady State (Tmin,ss) of SLV213 in Plasma After Dose 14 | 12.05 h |
Secondary
Total Clearance (CLT) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. CLT was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Total Clearance (CLT) of SLV213 in Plasma After Dose 1 | 179.0 L/h | Geometric Coefficient of Variation 65 |
Secondary
Vd at Steady State (Vd,ss) of SLV213 in Plasma After Dose 14
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 14 (the last dose) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Time frame: 0 h through 48 h post dose 14
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Vd at Steady State (Vd,ss) of SLV213 in Plasma After Dose 14 | 1079.1 L | Geometric Coefficient of Variation 73 |
Secondary
Volume of Distribution (Vd) of SLV213 in Plasma After Dose 1
PK parameters were estimated from the SLV213 plasma concentration-time data after dose 1 using Phoenix WinNonlin Non-compartmental analysis. Vd was estimated for parameters meeting the following lambda-z acceptance criteria: rsq\_adjusted (adjusted r squared) \>= 0.90 and includes at least 3 time points after Tmax.
Time frame: 0 h through 12 h post dose 1
Population: The PK population includes all randomized participants, including replacement participants, who received at least one dose of study treatment and have at least one quantifiable post-dosing plasma concentration to use for the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - 400 mg SLV213 | Volume of Distribution (Vd) of SLV213 in Plasma After Dose 1 | 555.5 L | Geometric Coefficient of Variation 63 |