A Phase 1, Open-Label, Fixed Sequence, Drug-Drug Interaction Study to Evaluate the Effects of Repeat Titrated Doses of Ecopipam on the Pharmacokinetics of Multiple Substrates for Drug Metabolism and Transport in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Ecopipam
- Conditions
- Drug Interaction
- Sponsor
- Emalex Biosciences Inc.
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a single center, open-label, fixed sequence Phase 1, drug-drug interaction (DDI) study in healthy subjects.
Detailed Description
Following a Screening period, eligible subjects will be enrolled sequentially to one of three cohorts to receive a single dose of probe substrate(s), followed by repeated titrated doses of ecopipam twice daily (BID) (with subjects in Cohort 3 also receiving a single dose of ecopipam and probe substrates on Day 4 prior to titration). After steady-state ecopipam dosing is reached, ecopipam will be co-administered with a single dose of probe substrate(s) (with continuation of ecopipam BID (every 12 h) dosing during the blood sampling period for the respective probe substrates), followed by an ecopipam tapering period and clinic discharge assessments.
Investigators
Eligibility Criteria
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
- •Subjects must be healthy, as determined by the Investigator, based on medical history, physical examination, ECG, and standard panel of blood and laboratory tests at Screening.
- •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
Arms & Interventions
Cohort 1
ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 1 Probe Substrate Cocktail given on 2 separate days: * midazolam: 1 µg infused IV * caffeine: 200 mg oral tablet * omeprazole: two 20 mg oral tablets * dextromethorphan: 1.6mL (containing \~10 mg) oral solution
Intervention: Ecopipam
Cohort 1
ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 1 Probe Substrate Cocktail given on 2 separate days: * midazolam: 1 µg infused IV * caffeine: 200 mg oral tablet * omeprazole: two 20 mg oral tablets * dextromethorphan: 1.6mL (containing \~10 mg) oral solution
Intervention: Cohort 1 Probe Substrate Cocktail
Cohort 2
ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 2 Probe Substrate given on 2 separate days: - bupropion: 100mg oral tablet
Intervention: Ecopipam
Cohort 2
ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 2 Probe Substrate given on 2 separate days: - bupropion: 100mg oral tablet
Intervention: Cohort 2 Probe Substrate
Cohort 3
ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 3 Probe Substrate Cocktail given on 3 separate days: * midazolam: 10 µg/mL given as 1mL oral solution. * dabigatran: 375 µg/mL and pitavastatin: 10 µg/mL given as 1mL oral solution * rosuvastatin: 25 µg/mL and atorvastatin: 50 µg/mL given as 2mL oral solution
Intervention: Ecopipam
Cohort 3
ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 3 Probe Substrate Cocktail given on 3 separate days: * midazolam: 10 µg/mL given as 1mL oral solution. * dabigatran: 375 µg/mL and pitavastatin: 10 µg/mL given as 1mL oral solution * rosuvastatin: 25 µg/mL and atorvastatin: 50 µg/mL given as 2mL oral solution
Intervention: Cohort 3 Probe Substrate Cocktail
Outcomes
Primary Outcomes
AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of dabigatran in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of dabigatran in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of rosuvastatin in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of rosuvastatin in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of dabigatran in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of rosuvastatin in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of rosuvastatin in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of rosuvastatin in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of rosuvastatin in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of dabigatran in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of rosuvastatin in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of rosuvastatin in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of dabigatran in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of dabigatran in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of dabigatran in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-24 of dabigatran in the absence of ecopipam
Time Frame: Up to Day 22
Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Secondary Outcomes
- Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam(Up to Day 22)
- AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam(Up to Day 22)
- CL for IV midazolam in the presence of ecopipam(Up to Day 22)
- CL/F for dabigatran in the presence of ecopipam(Up to Day 22)
- CL/F for rosuvastatin in the absence of ecopipam(Up to Day 22)
- CL/F for atorvastatin in the presence of ecopipam(Up to Day 22)
- CL/F for bupropion in the presence of ecopipam(Up to Day 22)
- CL/F for bupropion in the absence of ecopipam(Up to Day 22)
- CL/F for caffeine in the presence of ecopipam(Up to Day 22)
- CL/F for omeprazole in the presence of ecopipam(Up to Day 22)
- CL/F for omeprazole in the absence of ecopipam(Up to Day 22)
- Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam(Up to Day 22)
- AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam(Up to Day 22)
- CL/F for atorvastatin in the absence of ecopipam(Up to Day 22)
- CL/F for caffeine in the absence of ecopipam(Up to Day 22)
- Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam(Up to Day 22)
- CL/F for dabigatran in the absence of ecopipam(Up to Day 22)
- CL/F for pitavastatin in the presence of ecopipam(Up to Day 22)
- AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam(Up to Day 22)
- AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam(Up to Day 22)
- AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam(Up to Day 22)
- Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam(Up to Day 22)
- CL/F for dextromethorphan in the presence of ecopipam(Up to Day 22)
- CL/F for dextromethorphan in the absence of ecopipam(Up to Day 22)
- CL for IV midazolam in the absence of ecopipam(Up to Day 22)
- CL/F for oral midazolam in the presence of ecopipam(Up to Day 22)
- CL/F for oral midazolam in the absence of ecopipam(Up to Day 22)
- V/F for dextromethorphan in the presence of ecopipam(Up to Day 22)
- V for IV midazolam in the presence of ecopipam(Up to Day 22)
- V for IV midazolam in the absence of ecopipam(Up to Day 22)
- V/F for oral midazolam in the presence of ecopipam(Up to Day 22)
- V/F for oral midazolam in the absence of ecopipam(Up to Day 22)
- V/F for dabigatran in the presence of ecopipam(Up to Day 22)
- V/F for dextromethorphan in the absence of ecopipam(Up to Day 22)
- AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam(Up to Day 22)
- AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam(Up to Day 22)
- AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam(Up to Day 22)
- CL/F for pitavastatin in the absence of ecopipam(Up to Day 22)
- CL/F for rosuvastatin in the presence of ecopipam(Up to Day 22)
- V/F for dabigatran in the absence of ecopipam(Up to Day 22)
- V/F for rosuvastatin in the absence of ecopipam(Up to Day 22)
- V/F for bupropion in the presence of ecopipam(Up to Day 22)
- V/F for atorvastatin in the presence of ecopipam(Up to Day 22)
- V/F for pitavastatin in the presence of ecopipam(Up to Day 22)
- V/F for pitavastatin in the absence of ecopipam(Up to Day 22)
- V/F for rosuvastatin in the presence of ecopipam(Up to Day 22)
- V/F for bupropion in the absence of ecopipam(Up to Day 22)
- V/F for atorvastatin in the absence of ecopipam(Up to Day 22)
- V/F for caffeine in the presence of ecopipam(Up to Day 22)
- V/F for caffeine in the absence of ecopipam(Up to Day 22)
- V/F for omeprazole in the presence of ecopipam(Up to Day 22)
- V/F for omeprazole in the absence of ecopipam(Up to Day 22)
- Total concentration of bilirubin in the presence of ecopipam(Up to Day 18)
- Total concentration of bilirubin in the absence of ecopipam(Up to Day 18)
- AEs with relatedness associated with dextromethorphan(Up to Day 63)
- Unconjugated concentration of bilirubin in the presence of ecopipam(Up to Day 18)
- Unconjugated concentration of bilirubin in the absence of ecopipam(Up to Day 18)
- Conjugated concentration of bilirubin in the presence of ecopipam(Up to Day 18)
- Conjugated concentration of bilirubin in the absence of ecopipam(Up to Day 18)
- Average of the 8-hour plasma dextromethorphan: dextrorphan ratio in the presence of ecopipam(Up to Day 14)
- Average of the 12-hour plasma dextromethorphan: dextrorphan ratio in the presence of ecopipam(Up to Day 14)
- Average of the 6-hour plasma dextromethorphan: dextrorphan ratio in the presence of ecopipam(Up to Day 14)
- Average of the 6-hour plasma dextromethorphan: dextrorphan ratio in the absence of ecopipam(Up to Day 14)
- Average of the 8-hour plasma dextromethorphan: dextrorphan ratio in the absence of ecopipam(Up to Day 14)
- Average of the 8-hour plasma caffeine: paraxanthine metabolite ratio in the presence of ecopipam(Up to Day 14)
- Average of the 12-hour plasma caffeine: paraxanthine metabolite ratio in the presence of ecopipam(Up to Day 14)
- Average of the 12-hour plasma dextromethorphan: dextrorphan ratio in the absence of ecopipam(Up to Day 14)
- Average of the 6-hour plasma caffeine: paraxanthine metabolite ratio in the presence of ecopipam(Up to Day 14)
- Average of the 6-hour plasma caffeine: paraxanthine metabolite ratio in the absence of ecopipam(Up to Day 14)
- Average of the 8-hour plasma caffeine: paraxanthine metabolite ratio in the absence of ecopipam(Up to Day 14)
- Average of the 12-hour plasma caffeine: paraxanthine metabolite ratio in the absence of ecopipam(Up to Day 14)
- Safety and tolerability as demonstrated by the Modified Observer's Assessment of Alertness/Sedation (MOAA/S)(Up to Day 63)
- AEs with relatedness associated with IV midazolam(Up to Day 63)
- AEs with relatedness associated with oral midazolam(Up to Day 63)
- AEs with relatedness associated with atorvastatin(Up to Day 63)
- Absolute values of white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3)(Up to Day 26)
- Absolute values of hemoglobin (g/dL)(Up to Day 26)
- Absolute values of urine bilirubin and nitrite(Up to Day 26)
- Absolute values of urobilinogen (Eu/dL)(Up to Day 26)
- Change from Day -1 to Day of Discharge in magnesium, urea, phosphorus, calcium, glucose, and total, conjugated and unconjugated bilirubin (mg/dL)(Up to Day 26)
- Safety and tolerability as demonstrated by the Columbia Suicide Severity Rating Scale (C-SSRS)(Up to Day 63)
- AEs with relatedness associated with dabigatran(Up to Day 63)
- Absolute values of magnesium, urea, phosphorus, calcium, glucose, and total, conjugated and unconjugated bilirubin (mg/dL)(Up to Day 26)
- Absolute values of albumin and total protein (g/dL)(Up to Day 26)
- Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), creatinine phosphokinase (CPK), and creatinine (U/L)(Up to Day 26)
- Absolute values of urine specific gravity(Up to Day 26)
- Absolute values of urine pH(Up to Day 26)
- Absolute values of urine protein(Up to Day 26)
- Absolute values of urine ketones(Up to Day 26)
- Change from Day -1 to Day of Discharge white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3)(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine bilirubin and nitrite(Up to Day 26)
- Number of participants requiring concomitant medications(Up to Day 63)
- AEs with relatedness associated with pitavastatin(Up to Day 63)
- AEs with relatedness associated with rosuvastatin(Up to Day 63)
- AEs with relatedness associated with bupropion(Up to Day 63)
- AEs with relatedness associated with caffeine(Up to Day 63)
- AEs with relatedness associated with omeprazole(Up to Day 63)
- Change from Day -1 to Day of Discharge in sodium, potassium, chloride (mmol/L)(Up to Day 26)
- AEs with relatedness associated with ecopipam(Up to Day 63)
- Absolute values of hematocrit (percent)(Up to Day 26)
- Absolute values of Red blood cell (RBC) count (M/mm3)(Up to Day 26)
- Absolute values of sodium, potassium, chloride (mmol/L)(Up to Day 26)
- Absolute values of urine glucose(Up to Day 26)
- Absolute values of urine blood(Up to Day 26)
- Absolute values of urine leukocytes by dipstick(Up to Day 26)
- Change from Day -1 to Day of Discharge in hemoglobin (g/dL)(Up to Day 26)
- Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/mm3)(Up to Day 26)
- Change from Day -1 to Day of Discharge in hematocrit (percent)(Up to Day 26)
- Change from Day -1 to Day of Discharge in albumin and total protein (g/dL)(Up to Day 26)
- 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), and creatinine (U/L)(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine specific gravity(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine pH(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine glucose(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine protein(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine blood(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine ketones(Up to Day 26)
- Change from Day -1 to Day of Discharge in urobilinogen (Eu/dL)(Up to Day 26)
- Change from Day -1 to Day of Discharge in urine leukocytes by dipstick(Up to Day 26)
- Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds)(Up to Day 26)
- Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG)(Up to Day 26)
- Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds)(Up to Day 26)
- Absolute values of oral temperature (degrees Celsius)(Up to Day 26)
- Change from pre-dose for the respective day in oral temperature (degrees Celsius)(Up to Day 26)
- Change from Day 1 to Day of Discharge of mean corpuscular hemoglobin (MCH) (pg)(Up to Day 26)
- Absolute values of mean corpuscular hemoglobin concentration (MCHC) (g/dL)(Up to Day 26)
- Change from Day 1 to Day of Discharge of mean corpuscular hemoglobin concentration (MCHC) (g/dL)(Up to Day 26)
- Change from pre-dose for the respective day in SBP and DBP (mmHG)(Up to Day 26)
- Absolute values of mean corpuscular volume (MCV) (fL)(Up to Day 26)
- Absolute values of heart rate (beats/minute)(Up to Day 26)
- Change from pre-dose for the respective day in heart rate (beats/minute)(Up to Day 26)
- Absolute values of mean corpuscular hemoglobin (MCH) (pg)(Up to Day 26)
- Absolute values of respiratory rate (breaths/minute)(Up to Day 26)
- Change from Day 1 to Day of Discharge of mean corpuscular volume (MCV) (fL)(Up to Day 26)