Drug-Drug Interaction Study to Evaluate the Effects of Ecopipam on the Pharmacokinetics of Multiple Substrates

Drug-Interactions Clinical Trial

Official title:

A Phase 1, Open-Label, Fixed Sequence Drug-Drug Interaction Study to Evaluate the Effects of Repeat Doses of Ecopipam on the Pharmacokinetics of Multiple Substrates for Drug Metabolism and Transport in Healthy Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04764851
• Other study ID #: EBS-101-HV-101
• Status: Terminated
• Phase: Phase 1
• Start date: February 18, 2021
• Est. completion date: May 7, 2021

Study information

• Verified date: April 2021
• Source: Emalex Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, open-label, fixed sequence Phase 1, drug-drug interaction (DDI) study in healthy subjects.

Description:

Following a screening period of up to 28 days, subjects will be admitted to the clinical research unit into one of three cohorts. On the morning of Day 1, subjects in cohorts 1, 2, and 3 will receive fasted doses of probe substrate(s) per assigned cohort. On Day 5, Cohort 2 only will receive a second fasted dose of probe substrates. Subjects in cohorts 1, 2, and 3 will receive the final fasted dose of probe substrate(s) on Day 13. Fasted ecopipam administration will begin on Day 5 and will continue through Day 17 at ~2mg/kg for all cohorts. Ecopipam doses will be tapered starting on Day 18 by 25 mg/day increments until subjects are off drug, with final discharge occurring 24 hours after the ecopipam HCl dose has been reduced to 25 mg (Day 21, 23, or 25).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: May 7, 2021
• Est. primary completion date: April 2, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male subjects or female subjects of non-childbearing potential

• =18 and <55 years of age at the time of consent

• BMI >18.5 and <30 kg/m2 and a weight of =50 kg for males or =45 kg for females

• Sexually active males must use a double barrier method of contraception during the study and for at least 90 days after the last dose of study drug

• Male subjects must be willing not to donate sperm until 90 days following the last study drug administration

Exclusion Criteria:

• Personal or family History of significant medical illness

• Clinically significant abnormalities on screening tests/exams

• History of or significant risk of committing suicide

• Donation of plasma within 7 days prior to dosing

• Donation or significant loss of blood within 30 days prior to the first dosing

• Major surgery within 3 months or minor surgery within 1 month prior to admission

• Use of prohibited prescription, over-the-counter medications or natural health products

• Alcohol-based products 24 hours prior to admission

• Female subjects who are currently pregnant or lactating

• Positive pregnancy test

• Use of tobacco or nicotine products within 3 months prior to Screening

• Significant alcohol consumption

• History of drug abuse within the previous 2 years, or a positive drug screen

• History of allergy to study medications

• Undergoing abrupt discontinuation of alcohol or sedatives

• Not suitable for study in the opinion of the Principal Investigator

Related Conditions & MeSH terms

• Drug-Interactions

Intervention

Drug:
• ecopipam HCl ~2mg/kg/day
oral tablet

Combination Product:
• Cohort 1 Probe Cocktail
dextromethorphan, caffeine, omeprazole, and midazolam
• Cohort 2 Probe Cocktail
dabigatran, pitavastatin, rosuvastatin, atorvastatin, midazolam
• Cohort 3 Probe Cocktail
bupropion

Locations

Country	Name	City	State
United States	Syneos Health Clinical Research Services, LLC.	Miami	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Emalex Biosciences Inc.	Nuventra, Syneos Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of dabigatran in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of dabigatran in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of rosuvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of rosuvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of dabigatran in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of dabigatran in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Primary	AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUCinf of rosuvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUCinf of rosuvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of dabigatran in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of dabigatran in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of rosuvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of rosuvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Primary	AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic	Up to Day 18
Secondary	Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	Cmax of caffeine (and its metabolite paraxanthine) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	Cmax of caffeine (and its metabolite paraxanthine) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUCinf of caffeine (and its metabolite paraxanthine) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUCinf of caffeine (and its metabolite paraxanthine) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUClast of caffeine (and its metabolite paraxanthine) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUClast of caffeine (and its metabolite paraxanthine) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for dextromethorphan in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for dextromethorphan in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for IV midazolam in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for IV midazolam in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for oral midazolam in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for oral midazolam in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for dabigatran in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for dabigatran in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for pitavastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for pitavastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for rosuvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for rosuvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for atorvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for atorvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for bupropion in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for bupropion in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for caffeine in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for caffeine in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for omeprazole in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	CL/F for omeprazole in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for dextromethorphan in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for dextromethorphan in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for IV midazolam in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for IV midazolam in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for oral midazolam in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for oral midazolam in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for dabigatran in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for dabigatran in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for pitavastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for pitavastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for rosuvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for rosuvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for atorvastatin in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for atorvastatin in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for bupropion in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for bupropion in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for caffeine in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for caffeine in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for omeprazole in the presence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	V/F for omeprazole in the absence of ecopipam	Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 18
Secondary	Total concentration of bilirubin in the presence of ecopipam	Bilirubin sampling will occur on Day 1 and Day 13	Up to Day 13
Secondary	Total concentration of bilirubin in the absence of ecopipam	Bilirubin sampling will occur on Day 1 and Day 13	Up to Day 13
Secondary	Unconjugated concentration of bilirubin in the presence of ecopipam	Bilirubin sampling will occur on Day 1 and Day 13	Up to Day 13
Secondary	Unconjugated concentration of bilirubin in the absence of ecopipam	Bilirubin sampling will occur on Day 1 and Day 13	Up to Day 13
Secondary	Safety and tolerability as demonstrated by MOAA/S	Safety and tolerability measures will be recorded at the indicated timepoints.	Up to Day 55
Secondary	Safety and tolerability as demonstrated by C-SSRS	Safety and tolerability measures will be recorded at the indicated timepoints.	Up to Day 55
Secondary	Safety and tolerability as demonstrated by concomitant medications	Safety and tolerability measures will be recorded at the indicated timepoints.	Up to Day 55
Secondary	AEs with relatedness associated with dextromethorphan	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with IV midazolam	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with oral midazolam	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with dabigatran	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with pitavastatin	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with rosuvastatin	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with atorvastatin	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with bupropion	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with caffeine	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with omeprazole	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	AEs with relatedness associated with ecopipam	Subjects will be continually monitored for adverse events	Up to Day 55
Secondary	Absolute values of white blood cell (WBC) count (K/Ul)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)	Up to Day 25	Blood samples will be collected for the assessment of hematology parameters.
Secondary	Absolute values of platelets (K/uL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Absolute values of hematocrit (%)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Absolute values of hemoglobin (g/dL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Absolute values of Red blood cell (RBC) count (M/uL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Absolute values of albumin and total protein (g/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) (U/L)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Absolute values of urine specific gravity	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine pH	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine glucose	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine protein	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine blood	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine ketones	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine bilirubin, urobilinogen, and nitrite	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of urine leukocytes by dipstick	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in platelets (K/uL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in hematocrit (%)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in hemoglobin (g/dL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in albumin and total protein (g/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) (U/L)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine specific gravity	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine pH	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine glucose	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine protein	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine blood	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine ketones	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter)	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Change from Day -1 to Day of Discharge in urine leukocytes by dipstick	Urine samples will be collected for the assessment of urine parameters.	Up to Day 25
Secondary	Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds)	Twelve-lead ECGs will be obtained with the participant in a supine position after a rest of at least 5 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured.	Up to Day 25
Secondary	Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds)	Twelve-lead ECGs will be obtained with the participant in a supine position after a rest of at least 5 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured.	Up to Day 25
Secondary	Absolute values of oral temperature (degrees Celsius)	Temperature will be assessed as part of vital signs.	Up to Day 25
Secondary	Change from pre-dose for the respective day in oral temperature (degrees Celsius)	Temperature will be assessed as part of vital signs.	Up to Day 25
Secondary	Absolute values of heart rate (beats/minute)	Heart rate will be assessed as part of vital signs.	Up to Day 25
Secondary	Change from pre-dose for the respective day in heart rate (beats/minute)	Heart rate will be assessed as part of vital signs.	Up to Day 25
Secondary	Absolute values of respiratory rate (breaths/minute)	Respiratory rate will be assessed as part of vital signs.	Up to Day 25
Secondary	Change from pre-dose for the respective day in respiratory rate (breaths/minute)	Respiratory rate will be assessed as part of vital signs.	Up to Day 25
Secondary	Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG)	Blood pressure will be assessed as part of vital signs.	Up to Day 25
Secondary	Change from pre-dose for the respective day in SBP and DBP (mmHG)	Blood pressure will be assessed as part of vital signs.	Up to Day 25